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Trial record 1 of 1 for:    NCT02755272
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A Study of Pembrolizumab With Carboplatin and Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT02755272
Recruitment Status : Recruiting
First Posted : April 28, 2016
Last Update Posted : February 25, 2019
Sponsor:
Collaborator:
University of Wisconsin, Madison
Information provided by (Responsible Party):
Fox Chase Cancer Center

Tracking Information
First Submitted Date  ICMJE April 25, 2016
First Posted Date  ICMJE April 28, 2016
Last Update Posted Date February 25, 2019
Actual Study Start Date  ICMJE May 31, 2016
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2016)
  • Objective Response Rate [ Time Frame: Up to 24 months ]
    Evaluate antitumor activity by assessing the percentage of patients with evidence of complete response or partial response per RECIST 1.1 criteria.
  • Incidence of Treatment-Related Adverse Events [ Time Frame: From the first dose of study treatment until 30 days after discontinuation of study treatment. ]
    The safety and tolerability of Pembrolizumab in Combination with Carboplatin and Gemcitabine will be evaluated from the results of reported signs and symptoms, scheduled physical examinations, vital sign measurements, and clinical laboratory test results.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02755272 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2016)
  • Clinical Benefit Rate [ Time Frame: Up to 24 months ]
    Evaluate antitumor activity by assessing the percentage of patients with evidence of complete response, partial response, or stable disease per RECIST 1.1 criteria
  • Progression Free Survival [ Time Frame: From the start of treatment until progressive disease or date of death, whichever occurs first (assessed up to 60 months.) ]
    Evaluate antitumor activity by assessing the time interval from initiation of study drug until progressive disease or death whichever occurs first.
  • Overall Survival [ Time Frame: From the start of treatment until death (assessed up to 60 months.) ]
    Evaluation of the overall survival rate of patients
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 26, 2016)
  • Assessment of Association of PD-L1 Expression with Clinical Benefit Rate [ Time Frame: Up to 24 months ]
  • Assessment of Association of PD-L1 Expression with Progression Free Survival [ Time Frame: Up to 24 months ]
  • Assessment of Association of PD-L1 Expression with Overall Survival [ Time Frame: Up to 24 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study of Pembrolizumab With Carboplatin and Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer
Official Title  ICMJE A Randomized Phase II Clinical Trial Assessing the Efficacy and Safety of MK-3475 (Pembrolizumab) in Combination With Carboplatin and Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer
Brief Summary

The main purpose of this study is to see if Pembrolizumab in combination with chemotherapy (carboplatin and gemcitabine) is safe and effective in treating patients with metastatic triple negative breast cancer.

Pembrolizumab is a drug which may help the immune system to target and destroy cancer cells. Pembrolizumab has been approved by the FDA for the treatment of advanced melanoma and metastatic non-small cell lung cancer. However, it has not been approved as a treatment for breast cancer.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma Breast Stage IV
Intervention  ICMJE
  • Drug: Pembrolizumab
    IV Infusion of 200 mg given on day one of each 21 day treatment cycle.
    Other Names:
    • MK-3475
    • Keytruda
  • Drug: Carboplatin
    IV infusion of a calculated dose (AUC 2 mL/min) given on days one and eight of each 21 day treatment cycle.
    Other Name: Paraplatin
  • Drug: Gemcitabine
    IV infusion of 800 mg/m^2 given on days one and eight of each 21 day treatment cycle.
    Other Name: Gemzar
Study Arms  ICMJE
  • Experimental: Pembrolizumab with Standard Chemotherapy
    Pembrolizumab plus standard chemotherapy using carboplatin and gemcitabine.
    Interventions:
    • Drug: Pembrolizumab
    • Drug: Carboplatin
    • Drug: Gemcitabine
  • Active Comparator: Standard Chemotherapy Alone
    Standard chemotherapy alone using carboplatin and gemcitabine.
    Interventions:
    • Drug: Carboplatin
    • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 26, 2016)
87
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2024
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subject Inclusion Criteria for Part 1: Safety Run-in study

  1. Women diagnosed with pathologically confirmed metastatic triple negative invasive breast cancer (centrally confirmed immunophenotype negative for all three receptors ER, PR and HER2).
  2. Hormone receptor status (ER and PR) both ≤ 5% by immunohistochemistry, and HER2 status confirmed by means of immunohistochemistry (with 0 or 1+ indicating negative status) or fluorescence in situ hybridization (with amplification ratio < 2.0 indicating negative status).
  3. Have either Evaluable disease, or have measurable clinical disease: Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST (version v1.1).
  4. Age > 18 years.
  5. Disease stage: Unresectable metastatic disease.
  6. Patients received up to 2 prior regimens for their disease in the metastatic setting.
  7. Patients are candidates for chemotherapy with carboplatin and gemcitabine.
  8. ECOG performance status 0 - 2.
  9. Adequate organ function tests and hematologic indices within 10 days of registration.
  10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  11. Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  12. Signed written Informed Consent in accordance with regulatory and institutional guidelines

Subject Exclusion Criteria for Part 1: Safety Run-in study

  1. Patients participating in another trial of an investigational agent within 4 weeks of the first dose of the study.
  2. Patients who received prior therapy using carboplatin/gemcitabine within 12 months prior to enrollment or subjects whose tumor progressed while on treatment with carboplatin or cisplatin.
  3. Patients with baseline grade 2 neuropathy.
  4. Patients with Hormone-receptor positive breast cancer (ER and/or PR > 5%), and with HER-2 positive breast cancer (by means of immunohistochemistry with 3+ indicating positive status or fluorescence in situ hybridization with amplification ratio ≥2.0 indicating positive status).
  5. Diagnosis of immunosuppression or receiving steroid therapy or other immunosuppressive therapy within 4 weeks of the study.
  6. Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thryoxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study.
  7. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  8. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  9. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  10. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  11. Known additional malignancy that progressed and/or required treatment in the last 5 years. Except that for basal and squamous cell carcinoma of the skin or in situ cervical carcinoma that has completed potentially curative therapy.
  12. Life expectancy of less than 3 months.
  13. Patients known to be carriers of Human Immunodeficiency Virus (HIV1/2).
  14. Patients known to be carriers of hepatitis virus B and C.
  15. Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte -associated antigen-4 (CTLA-4) antibody.
  16. Pregnant, breastfeeding, or expecting to conceive children within the projected time of the trial, starting with the pre-screening or screening visit and through 120 days after the last dose of trial treatment.
  17. Active infection requiring systemic therapy.
  18. Active substance abuse or psychiatric disorders.
  19. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
  20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  21. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

Subject Inclusion Criteria for Part 2 (Randomized Phase II Clinical Trial)

  1. Women diagnosed with pathologically confirmed triple negative invasive breast cancer, metastatic (locally confirmed immunophenotype negative for all three receptors ER, PR, HER2).
  2. Hormone receptor status (ER and PR) both ≤ 5% by immunohistochemistry, and HER2 status confirmed by means of immunohistochemistry (with 0 or 1+ indicating negative status) or fluorescence in situ hybridization (with amplification ratio < 2.0 indicating negative status).
  3. Age > 18 years.
  4. Disease stage IV, metastatic unresectable disease.
  5. Have measurable clinical disease: Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST (version v1.1).
  6. Patients received up to 3 prior regimens for their metastatic disease. Prior hormone therapy will not be counted towards the line of therapies.
  7. Patients are candidates for chemotherapy with carboplatin and gemcitabine.
  8. ECOG performance status 0-2.
  9. Adequate organ function tests and hematologic indices within 10 days of registration.
  10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  12. Signed written Informed Consent in accordance with regulatory and institutional guidelines.
  13. Have provided tissue from a newly obtained biopsy (an archival tissue sample may be substituted if new biopsy cannot be obtained and by discretion of Principal Investigator only) from a local or distant site and agreed to providing a second newly obtained biopsy after completion of 2 cycles of the study drugs.

Subject Exclusion Criteria for Part 2 (Randomized Phase II Clinical Trial)

  1. Patients participating in another trial of an investigational agent within 4 weeks of the first dose of the study.
  2. Patients with tumors that cannot be measured or clinically followed (i.e. evaluable disease).
  3. Patients with metastatic breast cancer who received prior therapy using carboplatin/gemcitabine within 12months prior to their enrollment or subjects whose tumor progressed while on treatment with carboplatin or cisplatin.
  4. Patients with baseline grade 2 neuropathy.
  5. Patients with Hormone-receptor positive breast cancer (ER and/or PR > 5%), and with HER-2 positive breast cancer (by means of immunohistochemistry with 3+ indicating positive status or fluorescence in situ hybridization with amplification ratio ≥2.0 indicating positive status).
  6. Diagnosis of immunosuppression or receiving steroid therapy or other immunosuppressive therapy within 4 weeks of the study.
  7. Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thryoxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study.
  8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  9. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  10. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  11. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  12. Known additional malignancy that progressed and/or required treatment in the last 5 years. Except that for basal and squamous cell carcinoma of the skin or in situ cervical carcinoma that has completed potentially curative therapy.
  13. Life expectancy of less than 3 months.
  14. Patients known to be carriers of Human Immunodeficiency Virus (HIV1/2).
  15. Patients known to be carriers of hepatitis virus B and C .
  16. Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte -associated antigen-4 (CTLA-4) antibody.
  17. Pregnant, breastfeeding, or expecting to conceive children within the projected time of the trial, starting with the pre-screening or screening visit and through 120 days after the last dose of trial treatment.
  18. Active infection requiring systemic therapy.
  19. Active substance abuse or psychiatric disorders.
  20. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
  21. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  22. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  23. Subjects who do not consent to providing pre and post treatment tissue sample for future research would not be eligible to participate in the trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Elias Obeid, MD 215-728-2792 Elias.Obeid@fccc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02755272
Other Study ID Numbers  ICMJE BR-076
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fox Chase Cancer Center
Study Sponsor  ICMJE Fox Chase Cancer Center
Collaborators  ICMJE University of Wisconsin, Madison
Investigators  ICMJE
Principal Investigator: Elias Obeid, MD Fox Chase Cancer Center
PRS Account Fox Chase Cancer Center
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP