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A Study Of PF-05212384 In Combination With Other Anti-Tumor Agents and in Combination With Cisplatin in Patients With Triple Negative Breast Cancer in an Expansion Arm (TNBC)

Primary Purpose

Neoplasm

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

PF-05212384 (gedatolisib)

Docetaxel

Cisplatin

Dacomitinib

About this trial

This is an interventional basic science trial for Neoplasm focused on measuring Advanced cancer, solid tumors, PI3K, mTOR, PI3K/mTOR, metastatic, Triple Negative Breast Cancer (TNBC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Cisplatin Combination Expansion:

Arm 1:Patients with TNBC with no prior cytotoxic chemotherapy therapy in the metastatic setting; Arm 2: Patients with TNBC and one or two prior cytotoxic therapies in the metastatic setting.

Arm A: castrate resistant prostate cancer, advanced breast cancer, or non-small cell lunch cancer that are candidates for treatment with a docetaxel-based combination.
Arm B: Urothelial transitional cell cancer, triple negative breast cancer, ovarian cancer or non small cell lunch cancer that are candidates for a cisplatin-based combination.
Arm C: Her2+ breast cancer refractory to prior herceptin or lapatinib, her2+ esophagal-gastric cancer, head and neck squamous cell cancer, or non small cell lunch cancer that are candidates for treatment with a dacomitinib-based combination.
Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1.
Adequate bone marrow, renal and liver function.

Exclusion Criteria:

Prior therapy for Cisplatin Combination Expansion:
- Prior platinum (carboplatin or cisplatin) in either the adjuvant or metastatic setting;
- Prior radiation to >25% bone marrow as estimated by the Investigator.
Patients with known symptomatic brain metastases.
Chemotherapy, radiotherapy, biologics or investigational agent within 4 weeks of the lead-in dose.
Major surgery within 4 weeks of the baseline disease assessments.
>2 prior regimens containing cytotoxic chemotherapy in the metastatic setting.
Active bacterial, fungal or viral infection.
Uncontrolled or significant cardiovascular disease.

Sites / Locations

University of Alabama at Birmingham
University of Alabama at Birmingham
Ronald Reagan UCLA Medical Center
UCLA Hematology Oncology
Westwood Bowyer Clinic
UCSF Helen Diller Family Comprehensive Cancer Center
Santa Monica UCLA Medical Center & Orthopaedic Hospital
UCLA Hematology Oncology
University of Colorado Denver CTO (CTRC)
University of Colorado Hospital
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Dana Farber Cancer Institute
Harper Professional Building
Karmanos Cancer Institute
Fox Chase Cancer Center
Medical University of South Carolina/ University Hospital
Medical University of South Carolina
MUSC SCTR Research
MUSC Health East Cooper
MUSC Specialty Care-North
British Columbia Cancer Agency - Vancouver Centre
Princess Margaret Cancer Center
Istituto Europeo di Oncologia - Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative
Istituto Regina Elena Struttura Complessa Oncologia Medica A
Hospital Universitari Vall d'Hebron
Hospital Universitario 12 de Octubre
University College London Hospital, NIHR UCLH Clinical Research Facility
Oxford Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Arm A

Arm B

Arm C

Expansion Arm 1

Expansion Arm 2

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C

DLT was defined as any of the following adverse events (AEs) attributable to the combination: (1) hematologic: grade 4 neutropenia lasting >7 days; febrile neutropenia; grade >=3 neutropenia with infection; grade 3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade >=2 pneumonitis; grade>=3 toxicities, except pneumonitis, and excluding those that had not been maximally treated; persistent, intolerable toxicities which resulted in the failure to deliver at least 3 of the 4 doses of PF-05212384 for Arms A and B or at least 3 of the 4 doses of PF-05212384 and 75% of dacomitinib for Arm C during the first cycle; the persistent, intolerable toxicities which result in delay of the start of the second cycle by more than 2 weeks relative to the scheduled start; in an asymptomatic participant, the grade 3 QTc prolongation persists after correction of any reversible causes.

Percentage of Participants With Objective Response - Arm B Expansion

Percentage of participants with objective response based on the assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.

Secondary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Treatment Emergent AEs were those occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment, or those were seen prior to the start of study treatment but increased in Common Terminology Criteria for Adverse Events (CTCAE) grade after the start of study treatment and within 28 days after final dose of study treatment. AEs were graded by the investigator according to the CTCAE version 4.03 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.

Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) - Arms A, B, C and B Expansion

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology

Laboratory abnormalities were graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: anemia,hemoglobin increased, platelets, white blood cells, absolute neutrophils,lymphocyte count increased, lymphopenia.

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry

Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), total bilirubin, creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia.

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Urinalysis

Number of Participants With Vital Signs Data Meeting Pre-defined Criteria

Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in sitting position.

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)

Cmax is defined as maximum observed plasma concentration.

Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)

Cmax is defined as maximum observed plasma concentration.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Docetaxel in Combination With PF-05212384 - Plasma Docetaxel (Arm A)

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Tmax is defined as time to reach maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Tmax is defined as time to reach maximum observed plasma concentration.

Mean Serum Biomarkers for Glucose - Baseline

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This study employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Mean Serum Biomarkers for Glucose - End of Treatment

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Mean Serum Biomarkers for Insulin - Baseline

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Mean Serum Biomarkers for Insulin - End of Treatment

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Percentage of Participants With BRAF and KRAS Mutations in Population of Breast Cancer - Arms A and C

Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.

Percentage of Participants With BRAF and KRAS Mutations in Population of Non-Small Cell Lung Cancer - Arms A, B and C

Percentage of Participants With BRAF and KRAS Mutations in Population of Prostate Cancer - Arm A

Percentage of Participants With BRAF and KRAS Mutations in Population of Ovarian Cancer - Arm B

Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation category was BRAF mutation status. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.

Percentage of Participants With BRAF and KRAS Mutations in Population of Transitional Cell Carcinoma - Arm B

Percentage of Participants With BRAF and KRAS Mutations in Population of Triple Negative Breast Cancer - Arm B

Percentage of Participants With BRAF and KRAS Mutations in Population of Head and Neck Cancer - Arm C

Percentage of Participants With BRAF and KRAS Mutations in Population of Oesophageal Carcinoma - Arm C

Number of Participants With Maximum Increase From Baseline in Corrected QT (QTc) Interval

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized.

Number of Participants With Maximum Corrected QT (QTc) Interval Meeting Pre-defined Criteria

QT interval corrected using Fridericia's formula (QTcF) and Bazette's formula (QTcB): QT interval (time corresponding to the beginning of depolarization to re-polarization of the ventricles) divided by cube root of RR interval. Maximum QTcF was categorized as less than (<) 450 milliseconds (msec), 450 msec to 480 msec, 480 msec to 500 msec, and more than (>) 500 msec.

Percentage of Participants With Objective Response - Arm A

Percentage of participants with objective response based on the assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.

Percentage of Participants With Objective Response - Arm B

Percentage of Participants With Objective Response - Arm C

Clinical Benefit Response Rate - Arm B Expansion

Percent of participants with confirmed complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. SD was defined as not qualifying for CR, PR, Progressive Disease (PD).

Duration of Response - Arm B Expansion

Duration of response was calculated from first date of partial response (PR) or complete response (CR) to the date of progression or death due to any cause. In the event of no progression or death, the last tumor assessment date without progression was used in this calculation.

Progression Free Survival - Arm B Expansion

Progression free survival (PFS) defined as the time from first dose of study treatment to date of first documentation of progression or death due to any cause, whichever occurs first. PFS was calculated as first event date minus the date of first dose of study medication plus 1 . Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

Mean Observed Score Values for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion

European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.

Mean Change From Baseline for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion

Full Information

NCT ID

NCT01920061

First Posted

August 7, 2013

Last Updated

August 20, 2022

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01920061

Brief Title

A Study Of PF-05212384 In Combination With Other Anti-Tumor Agents and in Combination With Cisplatin in Patients With Triple Negative Breast Cancer in an Expansion Arm (TNBC)

Official Title

A PHASE 1B OPEN-LABEL THREE-ARM MULTI-CENTER STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF PF-05212384 (PI3K/MTOR INHIBITOR) IN COMBINATION WITH OTHER ANTI-TUMOR AGENTS

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

September 10, 2013 (Actual)

Primary Completion Date

January 8, 2020 (Actual)

Study Completion Date

January 8, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study will evaluate PF-05212384 (gedatolisib) PI3K/mTOR inhibitor)) in combination with either docetaxel, cisplatin or dacomitinib in select advanced solid tumors. The study will assess the safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer in order to determine the maximum tolerated dose in each combination. The cisplatin combination expansion portion will evaluate the anti tumor activity of PF 05212384 plus cisplatin in patients with TNBC in 2 separate Arms (Arm 1 and Arm 2).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neoplasm

Keywords

Advanced cancer, solid tumors, PI3K, mTOR, PI3K/mTOR, metastatic, Triple Negative Breast Cancer (TNBC)

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

110 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Title

Arm B

Arm Type

Experimental

Arm Title

Arm C

Arm Type

Experimental

Arm Title

Expansion Arm 1

Arm Type

Experimental

Arm Title

Expansion Arm 2

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

PF-05212384 (gedatolisib)

Intervention Description

PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

Docetaxel intravenous infusions once every 3 weeks starting at 75 mg/m^2

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2

Intervention Type

Drug

Intervention Name(s)

Dacomitinib

Intervention Description

Dacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg

Primary Outcome Measure Information:

Title

Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C

Description

Time Frame

Up to 21 days

Title

Percentage of Participants With Objective Response - Arm B Expansion

Description

Time Frame

Cycle 1 Day 1 up to 18 months

Secondary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion

Description

Time Frame

From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.

Title

Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) - Arms A, B, C and B Expansion

Description

Time Frame

Title

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology

Description

Time Frame

Title

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation

Description

Time Frame

Title

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry

Description

Time Frame

Title

Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Urinalysis

Description

Time Frame

Title

Number of Participants With Vital Signs Data Meeting Pre-defined Criteria

Description

Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in sitting position.

Time Frame

From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment). Maximum duration between first and last dose: 842 days.

Title

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.

Title

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)

Description

Cmax is defined as maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)

Description

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Time Frame

Title

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)

Description

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)

Description

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 2 Day 1.

Title

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)

Description

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Description

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.

Title

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Description

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.

Title

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)

Description

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Time Frame

Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Docetaxel in Combination With PF-05212384 - Plasma Docetaxel (Arm A)

Description

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Time Frame

Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)

Description

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Time Frame

Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)

Description

AUClast is defined as area under the curve from time zero to last quantifiable concentration.

Time Frame

Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)

Description

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time Frame

Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)

Description

AUCtau is defined as area under the concentration-time profile from time 0 to time tau.

Time Frame

Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)

Description

Tmax is defined as time to reach maximum observed plasma concentration.

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.

Title

Mean Serum Biomarkers for Glucose - Baseline

Description

Time Frame

Baseline

Title

Mean Serum Biomarkers for Glucose - End of Treatment

Description

Time Frame

End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.

Title

Mean Serum Biomarkers for Insulin - Baseline

Description

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Time Frame

Baseline

Title

Mean Serum Biomarkers for Insulin - End of Treatment

Description

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Time Frame

End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.

Title

Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline

Description

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Time Frame

Baseline

Title

Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment

Description

A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition.

Time Frame

End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Breast Cancer - Arms A and C

Description

Time Frame

Baseline

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Non-Small Cell Lung Cancer - Arms A, B and C

Description

Time Frame

Baseline

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Prostate Cancer - Arm A

Description

Time Frame

Baseline

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Ovarian Cancer - Arm B

Description

Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation category was BRAF mutation status. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.

Time Frame

Baseline

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Transitional Cell Carcinoma - Arm B

Description

Time Frame

Baseline

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Triple Negative Breast Cancer - Arm B

Description

Time Frame

Baseline

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Head and Neck Cancer - Arm C

Description

Time Frame

Baseline

Title

Percentage of Participants With BRAF and KRAS Mutations in Population of Oesophageal Carcinoma - Arm C

Description

Time Frame

Baseline

Title

Number of Participants With Maximum Increase From Baseline in Corrected QT (QTc) Interval

Description

Time Frame

Baseline, Cycle 1 Day 1 (for Arm B Expansion), Cycle 1 Day 2 (for Arms A, B and C), Cycle 2 Day 1 (for Arms A, B and C), Day 1 for each cycle (Cycles 3-36, for Arms B Expansion and C) and end of treatment (up to 2 years, for Arms B Expansion and C).

Title

Number of Participants With Maximum Corrected QT (QTc) Interval Meeting Pre-defined Criteria

Description

Time Frame

Title

Percentage of Participants With Objective Response - Arm A

Description

Time Frame

Baseline up to 18 months.

Title

Percentage of Participants With Objective Response - Arm B

Description

Time Frame

Baseline up to 18 months.

Title

Percentage of Participants With Objective Response - Arm C

Description

Time Frame

Baseline up to 18 months.

Title

Clinical Benefit Response Rate - Arm B Expansion

Description

Time Frame

Baseline up to 18 months.

Title

Duration of Response - Arm B Expansion

Description

Time Frame

Baseline up to 18 months.

Title

Progression Free Survival - Arm B Expansion

Description

Time Frame

Baseline up to 18 months.

Title

Mean Observed Score Values for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion

Description

Time Frame

Baseline, Day 1 and Day 8 of Cycles 1 and 2, Day 1 of Cycles 3 to 16.

Title

Mean Change From Baseline for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion

Description

Time Frame

Baseline, Day 1 and Day 8 of Cycles 1 and 2, Day 1 of Cycles 3 to 16.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Cisplatin Combination Expansion: Arm 1:Patients with TNBC with no prior cytotoxic chemotherapy therapy in the metastatic setting; Arm 2: Patients with TNBC and one or two prior cytotoxic therapies in the metastatic setting. Arm A: castrate resistant prostate cancer, advanced breast cancer, or non-small cell lunch cancer that are candidates for treatment with a docetaxel-based combination. Arm B: Urothelial transitional cell cancer, triple negative breast cancer, ovarian cancer or non small cell lunch cancer that are candidates for a cisplatin-based combination. Arm C: Her2+ breast cancer refractory to prior herceptin or lapatinib, her2+ esophagal-gastric cancer, head and neck squamous cell cancer, or non small cell lunch cancer that are candidates for treatment with a dacomitinib-based combination. Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available. Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1. Adequate bone marrow, renal and liver function. Exclusion Criteria: Prior therapy for Cisplatin Combination Expansion: Prior platinum (carboplatin or cisplatin) in either the adjuvant or metastatic setting; Prior radiation to >25% bone marrow as estimated by the Investigator. Patients with known symptomatic brain metastases. Chemotherapy, radiotherapy, biologics or investigational agent within 4 weeks of the lead-in dose. Major surgery within 4 weeks of the baseline disease assessments. >2 prior regimens containing cytotoxic chemotherapy in the metastatic setting. Active bacterial, fungal or viral infection. Uncontrolled or significant cardiovascular disease.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35233

Country

United States

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35249

Country

United States

Facility Name

Ronald Reagan UCLA Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

UCLA Hematology Oncology

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Westwood Bowyer Clinic

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

UCSF Helen Diller Family Comprehensive Cancer Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

Santa Monica UCLA Medical Center & Orthopaedic Hospital

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

UCLA Hematology Oncology

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

University of Colorado Denver CTO (CTRC)

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

University of Colorado Hospital

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Harper Professional Building

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Karmanos Cancer Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Fox Chase Cancer Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19111

Country

United States

Facility Name

Medical University of South Carolina/ University Hospital

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

MUSC SCTR Research

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

MUSC Health East Cooper

City

Mount Pleasant

State/Province

South Carolina

ZIP/Postal Code

29464

Country

United States

Facility Name

MUSC Specialty Care-North

City

North Charleston

State/Province

South Carolina

ZIP/Postal Code

29406

Country

United States

Facility Name

British Columbia Cancer Agency - Vancouver Centre

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 4E6

Country

Canada

Facility Name

Princess Margaret Cancer Center

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

Istituto Europeo di Oncologia - Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative

City

Milano

State/Province

ZIP/Postal Code

20141

Country

Italy

Facility Name

Istituto Regina Elena Struttura Complessa Oncologia Medica A

City

Roma

State/Province

ZIP/Postal Code

00144

Country

Italy

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Universitario 12 de Octubre

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

University College London Hospital, NIHR UCLH Clinical Research Facility

City

London

ZIP/Postal Code

W1T 7HA

Country

United Kingdom

Facility Name

Oxford Cancer Centre

City

Oxford

ZIP/Postal Code

OX3 7LE

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Citations:

PubMed Identifier

36335217

Citation

Curigliano G, Shapiro GI, Kristeleit RS, Abdul Razak AR, Leong S, Alsina M, Giordano A, Gelmon KA, Stringer-Reasor E, Vaishampayan UN, Middleton M, Olszanski AJ, Rugo HS, Kern KA, Pathan N, Perea R, Pierce KJ, Mutka SC, Wainberg ZA. A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer. Br J Cancer. 2023 Jan;128(1):30-41. doi: 10.1038/s41416-022-02025-9. Epub 2022 Nov 5. Erratum In: Br J Cancer. 2023 Jan;128(2):400.

Results Reference

derived

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B2151002&StudyName=A%20Study%20Of%20PF-05212384%20In%20Combination%20With%20Other%20Anti-Tumor%20Agents

Description

To obtain contact information for a study center near you, click here.

Learn more about this trial

A Study Of PF-05212384 In Combination With Other Anti-Tumor Agents and in Combination With Cisplatin in Patients With Triple Negative Breast Cancer in an Expansion Arm (TNBC)

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