Clinical Trials /

Phase 2 Study of Pembrolizumab+Carboplatin in Breast Related Cancer Antigens-related Metastatic Breast Cancer (PEMBRACA)

NCT03732391

Description:

This is a prospective two-stage single arm phase II study to be conducted in conformance with Good Clinical Practices. This study will enrol 53 patients, based on a two steps Simon's design. Patients will entry into the study if the following conditions will be satisfied: - BRCA1/2 germline mutations. - Metastatic disease with measurable lesions will be evaluated by computed tomography or by PET (Positron Emission Tomography) scan. - Patients must have received anthracycline and taxanes before entry into the study. Patients will be treated with Carboplatin AUC6 (Area Under The Curve) EV (endovenous) every 3 weeks in combination with Pembrolizumab 200 mg EV every 3 weeks for 6 cycles. Afterwards, the Pembrolizumab will recontinued with the same schedule until unacceptable toxicity or disease progression. The primary endpoint will be Objective Responses Rate (ORR) (complete answers + partial answers) evaluated according to the RECIST criteria.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of Pembrolizumab+Carboplatin in Breast Related Cancer Antigens-related Metastatic Breast Cancer (PEMBRACA)
  • Official Title: A Phase II Study of Pembrolizumab Plus Carboplatin in BRCA-related Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: PEMBRACA
  • NCT ID: NCT03732391

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
Pembrolizumab 25 MG(milligram)/MLCarboplatinsingle arm

Purpose

This is a prospective two-stage single arm phase II study to be conducted in conformance with Good Clinical Practices. This study will enrol 53 patients, based on a two steps Simon's design. Patients will entry into the study if the following conditions will be satisfied: - BRCA1/2 germline mutations. - Metastatic disease with measurable lesions will be evaluated by computed tomography or by PET (Positron Emission Tomography) scan. - Patients must have received anthracycline and taxanes before entry into the study. Patients will be treated with Carboplatin AUC6 (Area Under The Curve) EV (endovenous) every 3 weeks in combination with Pembrolizumab 200 mg EV every 3 weeks for 6 cycles. Afterwards, the Pembrolizumab will recontinued with the same schedule until unacceptable toxicity or disease progression. The primary endpoint will be Objective Responses Rate (ORR) (complete answers + partial answers) evaluated according to the RECIST criteria.

Trial Arms

NameTypeDescriptionInterventions
single armExperimentalCarboplatin AUC6 EV will be given every 3 weeks in combination with Pembrolizumab 200 mg EV every 3 weeks for 6 cycles. Afterwards, the Pembrolizumab will come continued with the same schedule until unacceptable toxicity or disease progression
  • Pembrolizumab 25 MG(milligram)/ML

Eligibility Criteria

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent/assent for the trial.

          2. Be 18 years of age on day of signing informed consent.

          3. Patients must have metastatic confirmed breast cancer

          4. Disease progression by radiological techniques within 12 months prior to signing
             informed consent

          5. Documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or
             suspected deleterious (unknown significance variants)

          6. Have measurable disease based on RECIST 1.1.

          7. Prior chemotherapy with anthracyclines and taxanes has to be administered in
             neoadjuvant or adjuvant setting.

          8. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived specimen

          9. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

         10. Life expectancy of greater than 3 months

         11. Demonstrate adequate organ function. All screening labs should be performed within 10
             days of treatment initiation.

         12. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

         13. Female subjects of childbearing potential must be willing to use an adequate method of
             contraception as outlined in Section 5.111.2 - Contraception, for the course of the
             study through 120 days after the last dose of study medication.

             Note: Abstinence is acceptable if this is the usual lifestyle and preferred
             contraception for the subject.

         14. Male subjects of childbearing potential must agree to use an adequate method of
             contraception as outlined in Section 5.11.2- Contraception, starting with the first
             dose of study therapy through 120 days after the last dose of study therapy.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          2. Has a benign variant of BRCA1/2 genes

          3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          4. Has a known history of active Bacillus Tuberculosis

          5. Hypersensitivity to pembrolizumab or any of its excipients.

          6. Has had a prior anti-cancer monoclonal antibody (mAb) 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.

          7. 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.

               -  Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study.

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting
                  therapy.

          8. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          9. 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. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

         10. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         11. Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

         12. Has an active infection requiring systemic therapy.

         13. 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.

         14. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         15. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

         16. Has received prior therapy with an anti-PD-1 (anti-programmed cell Death-1),
             anti-PD-L1, or anti-PD-L2 agent.

         17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV
             (Hepatitis C Virus) RNA [qualitative] is detected).

         19. Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live
             attenuated vaccines, and are not allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The ORR
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:objective response rate (complete response plus partial response) will be evaluated according to RECIST criteria

Secondary Outcome Measures

Measure:TTP (time to tumor progression)
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:(time to tumor progression)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:CORTESI LAURA

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