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A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer (PROFILE 1001)

Primary Purpose

Non-Small Cell Lung Cancer ALK-positive, Non-Small Cell Lung Cancer c-Met Dependent, Non-Small Cell Lung Cancer ROS Marker Positive

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

PF-02341066

Rifampin

Itraconazole

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer ALK-positive focused on measuring Crizotinib, dose-finding, drug-drug interaction, ALK rearrangements, c-Met mutations or amplifications, c-Met dependent tumors, ROS1 rearrangements, c-Met exon 14 deletion, c-Met exon 14 skipping, c-Met exon 14 alterations

Eligibility Criteria

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

Inclusion Criteria:

Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies.
Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis)

Exclusion Criteria:

Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort
Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma
Active or unstable cardiac disease or heart attack within 3 months of starting study treatment

Sites / Locations

University of California, Irvine Medical Center
University of Colorado Hospital/ Anschutz Cancer Pavilion
University of Colorado Hospital
University of Colorado
University of Chicago
Massachusetts General Hospital
Ophthalmic Consultants of Boston Inc.
Beth Israel Deaconess Medical Center
Dana Farber Cancer Center
Joslin Beetham Eye Institute
Karmanos Cancer Institute
Kresge Eye Institute
Memorial Sloan-Kettering Cancer Center
Memorial Sloan Kettering Cancer Center: Breast and Imaging Center
Memorial Sloan-Kettering Cancer Center
UNC Hospitals
The James Cancer Hospital and Solove Research Institute
Ohio State Eye and Ear Institute
The Ohio State University Martha Morehouse Medical Plaza
UPMC Hillman Cancer Center
Henry-Joyce Cancer Clinic
Vanderbilt Eye Institute
The University of Vermont Medical Center
The University of Vermont Cancer Center
Peter MacCallum Cancer Centre
Aichi cancer center central hospital
Hyogo Cancer Center
Kindai University Hospital
Seoul National University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

Dose-Escalation Cohort: Maximum Tolerated Dose (MTD) of Crizotinib

MTD: Dose level at which at most 1 of 6 participants experienced DLT within and including 28 days of treatment (during Cycle 1 [1 cycle=28 days]) with next higher dose having at least 2/3 or 2/6 participants experiencing a DLT. DLT was defined as any of following: Hematologic toxicities- 1) prolonged grade 4 neutropenia for >7 days. 2) Febrile neutropenia: grade 4 neutropenia with fever greater than (>) 38.5 degree Celsius, both sustained over a 24 hour period (3) neutropenic infection: greater than or equal to (>=) Grade 3 neutropenia with Grade >=3 infection. (4) Grade >=3 thrombocytopenia with bleeding/grade 4 lasting >=7 days. Other non-hematologic toxicity included: Grade 3/4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure [less than (<) 140/90 millimeter of mercury, and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting/diarrhea must persist at grade 3/4 despite maximal medical therapy.

Dose-Escalation Cohort: Recommended Phase 2 Dose (RP2D) of Crizotinib

RP2D was defined as a dose below or equal to MTD, at which crizotinib was unlikely to cause a significant inhibition of CYP3A4 activity.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Crizotinib on Day -7

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (0-inf).

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Day -7

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 1

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 15

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 2 Day 1

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib Cycle 1 Day 15

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib on Cycle 2 Day 1

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Day -7

Cmax is defined as the observed maximum plasma concentration post drug administration.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 1

Cmax is defined as the observed maximum plasma concentration post drug administration.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 15

Cmax is defined as the observed maximum plasma concentration post drug administration.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 2 Day 1

Cmax is defined as the observed maximum plasma concentration post drug administration.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Day -7

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 1

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 15

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib Cycle 2 Day 1

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Plasma Decay Half-Life (t1/2) of Crizotinib on Day -7

Plasma decay half-life is the time measured for the plasma concentration of Crizotinib to decrease by one half.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Number of Participants With Treatment Emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. AEs included both serious and all non-serious adverse events. TEAEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration.

Dose-Escalation Cohort: Number of Participants With Dose-limiting Toxicities (DLT)

Dose-limiting toxicity (DLT) was defined as any of the following: Hematologic- prolonged grade 4 neutropenia for >7 days. Febrile neutropenia, defined as grade 4 neutropenia with fever greater than (>)38.5 degree Celsius, both sustained over a 24 hour period, neutropenic infection: greater than or equal to (>=)Grade 3 neutropenia with Grade >=3 infection. Grade >=3 thrombocytopenia with bleeding or grade 4 lasting >=7 days Lymphopenia was not considered a DLT unless accompanied by infection. Other non-hematologic toxicity: Grade 3 or 4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure [less than (<) 140/90], and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea must persist at grade 3 or 4 despite maximal medical therapy.

Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib

Cmax is defined as the observed maximum plasma concentration post drug administration.

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam When Taken Alone or Taken With Crizotinib

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

RP2D Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Crizotinib When Taken With Food

AUC0-24 of Crizotinib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.

RP2D Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken With Food

Cmax is defined as the observed maximum plasma concentration post drug administration.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib Alone and When Taken With Rifampin

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau).

Rifampin Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib Alone and When Taken With Rifampin

Rifampin Cohort: Ctrough of Crizotinib Alone and When Taken With Rifampin

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Itraconazole Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib When Taken Alone and When Taken With Itraconazole

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.

Itraconazole Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken Alone and When Taken With Itraconazole

Itraconazole Cohort: Trough Plasma Concentration (Ctrough) of Crizotinib When Taken Alone and When Taken With Itraconazole

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Objective Response (OR)

ORR was defined as participants with a best overall response of complete response (CR) or partial response (PR) divided by the total number of evaluable participants per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response.

Recommended Phase 2 Dose (RP2D) Cohort: Duration of Response (DOR)

Duration of response (DoR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PD: >=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Recommended Phase 2 Dose (RP2D) Cohort: Time to Response (TTR)

TTR: time between first dose until first documented response of PR or CR. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response.

Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 8

Disease control was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 16

Recommended Phase 2 Dose (RP2D) Cohort: Progression Free Survival (PFS)

Progression free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PD: >=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Recommended Phase 2 Dose (RP2D) Cohort: Probability of Being Event Free at Month 6

Probability of being event free (event defined as PD or death due to any cause) at 6 months after the first dose of crizotinib was reported. PD: >=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Recommended Phase 2 Dose (RP2D) Cohort: Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause.

Probability of Participant Survival at Month 6

Probability of survival was defined as the probability of being alive at Month 6.

Probability of Participant Survival at Month 12

Probability of survival was defined as the probability of being alive at Month 12.

Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 1 Day 15

Geometric mean of ratio (Cycle1Day15/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Geometric mean of ratio (Cycle 2 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Geometric mean of ratio (Cycle 4 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Geometric mean of ratio (Cycle 6 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Geometric mean of ratio (Cycle 9 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (Cycle 12 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (Cycle 15 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (Cycle 18 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (Cycle 21 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (Cycle 24 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (Cycle 27 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (Cycle 30 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Geometric mean of ratio (End of treatment/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Secondary Outcome Measures

Full Information

NCT ID

NCT00585195

First Posted

December 29, 2007

Last Updated

January 10, 2023

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00585195

Brief Title

A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

Acronym

PROFILE 1001

Official Title

PHASE 1 SAFETY, PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF PF-02341066, A MET/HGFR SELECTIVE TYROSINE KINASE INHIBITOR, ADMINISTERED ORALLY TO PATIENTS WITH ADVANCED CANCER

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

April 19, 2006 (Actual)

Primary Completion Date

July 30, 2020 (Actual)

Study Completion Date

January 19, 2022 (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

PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.

6. Conditions and Keywords

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

Non-Small Cell Lung Cancer ALK-positive, Non-Small Cell Lung Cancer c-Met Dependent, Non-Small Cell Lung Cancer ROS Marker Positive, Systemic Anaplastic Large-Cell Lymphoma, Advanced Malignancies Except Leukemia

Keywords

Crizotinib, dose-finding, drug-drug interaction, ALK rearrangements, c-Met mutations or amplifications, c-Met dependent tumors, ROS1 rearrangements, c-Met exon 14 deletion, c-Met exon 14 skipping, c-Met exon 14 alterations

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

596 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

PF-02341066

Intervention Description

Escalating doses of PF-02341066 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg to 2000 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days (or 21 days depending on the cohort).

Intervention Type

Drug

Intervention Name(s)

Rifampin

Intervention Description

600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066.

Intervention Type

Drug

Intervention Name(s)

Itraconazole

Intervention Description

Multiple Dose Design: 200 mg QD administered from Cycle 1, Day 1 to Cycle 1, Day 16 (16 days) in combination with PF-02341066.

Primary Outcome Measure Information:

Title

Dose-Escalation Cohort: Maximum Tolerated Dose (MTD) of Crizotinib

Description

Time Frame

Cycle 1 (28 days)

Title

Dose-Escalation Cohort: Recommended Phase 2 Dose (RP2D) of Crizotinib

Description

RP2D was defined as a dose below or equal to MTD, at which crizotinib was unlikely to cause a significant inhibition of CYP3A4 activity.

Time Frame

Cycle 1 (28 days)

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Crizotinib on Day -7

Description

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (0-inf).

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Day -7

Description

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 1

Description

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time Frame

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

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 15

Description

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 2 Day 1

Description

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib Cycle 1 Day 15

Description

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time Frame

Pre-dose on Cycle 1 Day 15

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib on Cycle 2 Day 1

Description

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time Frame

Pre-dose on Cycle 2 Day 1

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Day -7

Description

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 1

Description

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time Frame

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

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 15

Description

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 2 Day 1

Description

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Day -7

Description

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 1

Description

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time Frame

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

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 15

Description

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib Cycle 2 Day 1

Description

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Plasma Decay Half-Life (t1/2) of Crizotinib on Day -7

Description

Plasma decay half-life is the time measured for the plasma concentration of Crizotinib to decrease by one half.

Time Frame

Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Title

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Number of Participants With Treatment Emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)

Description

Time Frame

up to 189 Months

Title

Dose-Escalation Cohort: Number of Participants With Dose-limiting Toxicities (DLT)

Description

Time Frame

Cycle 1 (28 days)

Title

Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib

Description

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time Frame

pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam When Taken Alone or Taken With Crizotinib

Description

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

Time Frame

pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

Title

RP2D Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Crizotinib When Taken With Food

Description

AUC0-24 of Crizotinib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.

Time Frame

pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7

Title

RP2D Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken With Food

Description

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time Frame

pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7

Title

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib Alone and When Taken With Rifampin

Description

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau).

Time Frame

pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)

Title

Rifampin Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib Alone and When Taken With Rifampin

Time Frame

pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone) and Cycle 2 Day 1 (Crizotinib with Rifampin)

Title

Rifampin Cohort: Ctrough of Crizotinib Alone and When Taken With Rifampin

Description

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time Frame

pre-dose on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)

Title

Itraconazole Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib When Taken Alone and When Taken With Itraconazole

Description

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.

Time Frame

pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

Title

Itraconazole Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken Alone and When Taken With Itraconazole

Time Frame

pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

Title

Itraconazole Cohort: Trough Plasma Concentration (Ctrough) of Crizotinib When Taken Alone and When Taken With Itraconazole

Description

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time Frame

pre-dose on Cycle 1 Day 15 (crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

Title

Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Objective Response (OR)

Description

Time Frame

Baseline up to 172 months

Title

Recommended Phase 2 Dose (RP2D) Cohort: Duration of Response (DOR)

Description

Time Frame

From first documentation of response to date of PD or death due to any cause (up to 172 months)

Title

Recommended Phase 2 Dose (RP2D) Cohort: Time to Response (TTR)

Description

Time Frame

From first dose until first documented response of PR or CR (up to 172 months)

Title

Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 8

Description

Time Frame

Week 8

Title

Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 16

Description

Time Frame

Week 16

Title

Recommended Phase 2 Dose (RP2D) Cohort: Progression Free Survival (PFS)

Description

Time Frame

From randomization until PD or death, whichever occurred first (up to 172 months)

Title

Recommended Phase 2 Dose (RP2D) Cohort: Probability of Being Event Free at Month 6

Description

Time Frame

From randomization to 6 months

Title

Recommended Phase 2 Dose (RP2D) Cohort: Overall Survival (OS)

Description

OS was defined as the time from randomization to death due to any cause.

Time Frame

From randomization date to the date of death (up to 172 Months)

Title

Probability of Participant Survival at Month 6

Description

Probability of survival was defined as the probability of being alive at Month 6.

Time Frame

Month 6

Title

Probability of Participant Survival at Month 12

Description

Probability of survival was defined as the probability of being alive at Month 12.

Time Frame

Month 12

Title

Description

Time Frame

Baseline, Cycle 1 Day 15

Title

Description

Time Frame

Baseline, Cycle 2 Day 1

Title

Description

Time Frame

Baseline, Cycle 4 Day 1

Title

Description

Time Frame

Baseline, Cycle 6 Day 1

Title

Description

Time Frame

Baseline, Cycle 9 Day 1

Title

Description

Time Frame

Baseline, Cycle 12 Day 1

Title

Description

Time Frame

Baseline, Cycle 15 Day 1

Title

Description

Time Frame

Baseline, Cycle 18 Day 1

Title

Description

Time Frame

Baseline, Cycle 21 Day 1

Title

Description

Time Frame

Baseline, Cycle 24 Day 1

Title

Description

Time Frame

Baseline, Cycle 27 Day 1

Title

Description

Time Frame

Baseline, Cycle 30 Day 1

Title

Description

Time Frame

Baseline, End of Treatment (28 days post last dose)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies. Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis) Exclusion Criteria: Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma Active or unstable cardiac disease or heart attack within 3 months of starting study treatment

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 California, Irvine Medical Center

City

Orange

State/Province

California

ZIP/Postal Code

92868-3201

Country

United States

Facility Name

University of Colorado Hospital/ Anschutz Cancer Pavilion

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

University of Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

University of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Ophthalmic Consultants of Boston Inc.

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

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 Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Joslin Beetham Eye Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Karmanos Cancer Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Kresge Eye Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10022

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center: Breast and Imaging Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

UNC Hospitals

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599-7600

Country

United States

Facility Name

The James Cancer Hospital and Solove Research Institute

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Ohio State Eye and Ear Institute

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43212

Country

United States

Facility Name

The Ohio State University Martha Morehouse Medical Plaza

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43221

Country

United States

Facility Name

UPMC Hillman Cancer Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

Facility Name

Henry-Joyce Cancer Clinic

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Vanderbilt Eye Institute

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

The University of Vermont Medical Center

City

Burlington

State/Province

Vermont

ZIP/Postal Code

05401

Country

United States

Facility Name

The University of Vermont Cancer Center

City

Burlington

State/Province

Vermont

ZIP/Postal Code

05405

Country

United States

Facility Name

Peter MacCallum Cancer Centre

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3000

Country

Australia

Facility Name

Aichi cancer center central hospital

City

Nagoya

State/Province

Aichi

ZIP/Postal Code

464-8681

Country

Japan

Facility Name

Hyogo Cancer Center

City

Akashi

State/Province

Hyogo

ZIP/Postal Code

673-8558

Country

Japan

Facility Name

Kindai University Hospital

City

Osakasayama

State/Province

Osaka

ZIP/Postal Code

589-8511

Country

Japan

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

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.

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Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A8081001&StudyName=A%20Study%20Of%20Oral%20PF-02341066%2C%20A%20c-Met/Hepatocyte%20Growth%20Factor%20Tyrosine%20Kinase%20Inhibitor%2C%20In%20Patients%20With%20Advanced%20Cancer

Description

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Learn more about this trial

A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

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