Clinical Trials /

A Study of Pembrolizumab With Carboplatin and Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer

NCT02755272

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Pembrolizumab With Carboplatin and Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BR-076
  • NCT ID: NCT02755272

Conditions

  • Carcinoma Breast Stage IV

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KeytrudaPembrolizumab with Standard Chemotherapy
CarboplatinParaplatinPembrolizumab with Standard Chemotherapy
GemcitabineGemzarPembrolizumab with Standard Chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab with Standard ChemotherapyExperimentalPembrolizumab plus standard chemotherapy using carboplatin and gemcitabine.
  • Pembrolizumab
  • Carboplatin
  • Gemcitabine
Standard Chemotherapy AloneActive ComparatorStandard chemotherapy alone using carboplatin and gemcitabine.
  • Carboplatin
  • Gemcitabine

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Evaluate antitumor activity by assessing the percentage of patients with evidence of complete response or partial response per RECIST 1.1 criteria.

Secondary Outcome Measures

Measure:Clinical Benefit Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Evaluate antitumor activity by assessing the percentage of patients with evidence of complete response, partial response, or stable disease per RECIST 1.1 criteria
Measure: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.)
Safety Issue:
Description:Evaluate antitumor activity by assessing the time interval from initiation of study drug until progressive disease or death whichever occurs first.
Measure:Overall Survival
Time Frame:From the start of treatment until death (assessed up to 60 months.)
Safety Issue:
Description:Evaluation of the overall survival rate of patients

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fox Chase Cancer Center

Trial Keywords

  • Triple Negative Breast Cancer

Last Updated

May 6, 2020