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Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer

Primary Purpose

Metastatic Triple Negative Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Nab-paclitaxel
Pembrolizumab
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Triple Negative Breast Cancer focused on measuring Carboplatin, Nab-Paclitaxel, Pembrolizumab

Eligibility Criteria

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

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed metastatic triple negative breast cancer
  • Subjects must have received no more than 2 prior therapies for this disease
  • ECOG Performance Status 0-1

  • Subjects must have normal organ and marrow function as defined below:

    • Hemoglobin ≥ 10.0 g/dl
    • Absolute neutrophil count ≥ 1,000/μL
    • Platelet count ≥ 100,000/μL
    • Total bilirubin within normal institutional limits
    • AST (SGOT) ≤ 2.5 X institutional upper limit of normal
    • ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
    • Serum creatinine ≤ 1.5 normal institutional limits
  • Life expectancy of 12 weeks or more
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • Subjects must have measurable disease per RECIST v1.1
  • Subjects must be willing to undergo a preliminary biopsy of a metastatic focus for research purposes. A second post-treatment biopsy will be offered but will not be mandated

Exclusion Criteria:

  • Prior treatment toxicities have not resolved to ≤ Grade 1 according to NCI CTCAE Version 4.0 (except for alopecia and neuropathy)
  • Subjects receiving any other investigational agents
  • Subjects with radiographically stable treated brain metastases are eligible but must not have been on steroid therapy for at least 4 weeks
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, carboplatin, pembrolizumab, or other agents used in this study
  • Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breastfeeding women are excluded from this study
  • Patients with conditions requiring immunosuppressive medications or chronic infections (including HIV infection, hepatitis B and C)
  • Patients with chronic autoimmune disease
  • Patients with prior therapy with antibodies that modulate T-cell function (e.g., anti-PD-1, anti-PD-L1)
  • Patients with evidence of active, non-infectious pneumonia
  • Patients active infection requiring intravenous systemic therapy
  • Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with requirements of the trial
  • Patients who have received a live vaccine within 30 days prior to the first dose of pembrolizumab
  • Patients with a known additional malignancy that is progressing or requires active treatment (within the last 5 years). Exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy
  • Patients who have received monoclonal anti-cancer antibody within 4 weeks of first dose of study drugs
  • Patients who have received chemotherapy, small molecule targeted therapy or radiation within the 2 weeks of first dose of study drugs
  • Patients who have participated in MK-3475 Merck studies
  • Patients with carcinomatous meningitis

Sites / Locations

  • University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Carboplatin + Nab-paclitaxel + Pembrolizumab

Arm Description

Combination therapy of Carboplatin, Nab-paclitaxel, and Pembrolizumab

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR) in Patients Treated With CNP
The number of people with tumor responses according to RECIST (V1.1). These responses include Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study

Secondary Outcome Measures

Progression-free Survival (PFS) in Patients Treated With CNP
Average time (in months) patient's tumors did not progress according to the RECIST criteria (V1.1). Progressive disease is defined as Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm
Disease Control Rate (DCR) in Patients Treated With CNP
the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention. Responses are defined as Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Duration of Response in Patients Treated With CNP
Average time patients have a response, as defined by the RECIST criteria (V1.1). Response includes: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Full Information

First Posted
March 30, 2017
Last Updated
October 5, 2023
Sponsor
Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03121352
Brief Title
Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer
Official Title
Pilot Study of Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
May 19, 2017 (Actual)
Primary Completion Date
February 20, 2022 (Actual)
Study Completion Date
May 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to see how effective the combination of the two chemotherapy drugs (carboplatin and nab-paclitaxel) are when added to a third drug, pembrolizumab. Pembrolizumab is an investigational (experimental) drug that works by reinvigorating the immune system, allowing it to target and destroy cancer cells. Pembrolizumab is experimental because it is not approved by the Food and Drug Administration (FDA) for this type of breast cancer treatment.
Detailed Description
Primary Objective - Determine overall response rate (ORR) in patients treated with CNP Secondary Objective(s) Determine progression-free survival (PFS), and disease control rate (DCR) in patients treated with CNP. Determine duration of response in patients treated with CNP. Determine safety/tolerability of CNP. Correlative Endpoints - Identify pathologic and genomic correlates of response to CNP. Study design including dose escalation / cohorts This is prospective pilot clinical trial of CNP in up to 30 patients with mTNBC

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Triple Negative Breast Cancer
Keywords
Carboplatin, Nab-Paclitaxel, Pembrolizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carboplatin + Nab-paclitaxel + Pembrolizumab
Arm Type
Experimental
Arm Description
Combination therapy of Carboplatin, Nab-paclitaxel, and Pembrolizumab
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
AUC 4.5 IV day 1 of 21-day cycle
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
75mg/m2 IV days 1, 8 and 15 of 21-day cycle
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475
Intervention Description
200 mg IV every 21 days
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) in Patients Treated With CNP
Description
The number of people with tumor responses according to RECIST (V1.1). These responses include Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS) in Patients Treated With CNP
Description
Average time (in months) patient's tumors did not progress according to the RECIST criteria (V1.1). Progressive disease is defined as Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm
Time Frame
Up to 24 months
Title
Disease Control Rate (DCR) in Patients Treated With CNP
Description
the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention. Responses are defined as Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Time Frame
Up to 24 months
Title
Duration of Response in Patients Treated With CNP
Description
Average time patients have a response, as defined by the RECIST criteria (V1.1). Response includes: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have histologically or cytologically confirmed metastatic triple negative breast cancer Subjects must have received no more than 2 prior therapies for this disease ECOG Performance Status 0-1 Subjects must have normal organ and marrow function as defined below: Hemoglobin ≥ 10.0 g/dl Absolute neutrophil count ≥ 1,000/μL Platelet count ≥ 100,000/μL Total bilirubin within normal institutional limits AST (SGOT) ≤ 2.5 X institutional upper limit of normal ALT (SGPT) ≤ 2.5 X institutional upper limit of normal Serum creatinine ≤ 1.5 normal institutional limits Life expectancy of 12 weeks or more Subjects must have the ability to understand and the willingness to sign a written informed consent document Subjects must have measurable disease per RECIST v1.1 Subjects must be willing to undergo a preliminary biopsy of a metastatic focus for research purposes. A second post-treatment biopsy will be offered but will not be mandated Exclusion Criteria: Prior treatment toxicities have not resolved to ≤ Grade 1 according to NCI CTCAE Version 4.0 (except for alopecia and neuropathy) Subjects receiving any other investigational agents Subjects with radiographically stable treated brain metastases are eligible but must not have been on steroid therapy for at least 4 weeks History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, carboplatin, pembrolizumab, or other agents used in this study Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant or breastfeeding women are excluded from this study Patients with conditions requiring immunosuppressive medications or chronic infections (including HIV infection, hepatitis B and C) Patients with chronic autoimmune disease Patients with prior therapy with antibodies that modulate T-cell function (e.g., anti-PD-1, anti-PD-L1) Patients with evidence of active, non-infectious pneumonia Patients active infection requiring intravenous systemic therapy Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with requirements of the trial Patients who have received a live vaccine within 30 days prior to the first dose of pembrolizumab Patients with a known additional malignancy that is progressing or requires active treatment (within the last 5 years). Exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy Patients who have received monoclonal anti-cancer antibody within 4 weeks of first dose of study drugs Patients who have received chemotherapy, small molecule targeted therapy or radiation within the 2 weeks of first dose of study drugs Patients who have participated in MK-3475 Merck studies Patients with carcinomatous meningitis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Baar, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer

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