Clinical Trials /

Carboplatin +/- Nivolumab in Metastatic Triple Negative Breast Cancer

NCT03414684

Description:

This research study is studying a drug called Carboplatin with or without another study drug, Nivolumab as a possible treatment for triple-negative breast cancer that has spread to other parts of the body. The interventions involved in this study are: - Carboplatin - Nivolumab

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Carboplatin +/- Nivolumab in Metastatic Triple Negative Breast Cancer
  • Official Title: A Randomized Phase II Trial of Carboplatin With or Without Nivolumab in First- or Second-line Metastatic Triple-negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-512
  • SECONDARY ID: CA209-9JX
  • NCT ID: NCT03414684

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
CarboplatinCarboplatin + Nivolumab
NivolumabOpdivoCarboplatin + Nivolumab

Purpose

This research study is studying a drug called Carboplatin with or without another study drug, Nivolumab as a possible treatment for triple-negative breast cancer that has spread to other parts of the body. The interventions involved in this study are: - Carboplatin - Nivolumab

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational intervention to learn whether the intervention works
      in treating a specific disease. "Investigational" means that the intervention is being
      studied.

      The FDA (the U.S. Food and Drug Administration) has not approved nivolumab for your specific
      disease but it has been approved for other uses. The FDA has approved carboplatin as a
      treatment option for your disease.

      The purpose of this research study is to determine how well carboplatin, by itself, or
      together with nivolumab, works in treating breast cancer that has spread to other parts of
      the body. Nivolumab is a recently discovered human monoclonal antibody. An antibody is a type
      of protein that your immune system (the system that defends your body against potentially
      harmful particles) uses to find and destroy foreign molecules (particles not typically found
      in your body, such as bacteria and viruses). Scientists can now make antibodies in the
      laboratory and produce them for the treatment of many different diseases.

      Nivolumab works by attaching to and blocking a molecule called PD-1. PD-1 is a different
      molecule that can turn off the immune system by interacting with PD-L1 on the cancer cell.
      Nivolumab has been shown in research studies to prevent PD-1 from shutting down the immune
      system, thus allowing it to recognize and help your body destroy the cancer cells. You are
      being asked to participate in this study because triple-negative breast cancer has shown
      elevated rates of PD-L1 expression.

      Nivolumab has been used in other research studies and information from those research studies
      suggests that nivolumab may help shrink or stabilize your triple negative breast cancer in
      this study
    

Trial Arms

NameTypeDescriptionInterventions
Carboplatin + NivolumabExperimentalNivolumab is administered every three weeks intravenously Nivolumab dosage is 360mg Carboplatin is administered every three weeks intravenously Carboplatin dosage is pre-determined by the PI
  • Carboplatin
  • Nivolumab
CarboplatinExperimentalCarboplatin is administered every three weeks intravenously Carboplatin dosage is pre-determined by the PI
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed invasive breast
             cancer, with unresectable locally advanced or metastatic disease. Participants without
             pathologic or cytologic confirmation of metastatic disease should have unequivocal
             evidence of metastasis from physical examination or radiologic evaluation.

          -  Estrogen-receptor and progesterone-receptor expression both ≤ 1% by
             immunohistochemistry (IHC), and HER2-negative status as determined by the current
             ASCO/CAP guidelines. If a patient has more than one histological result, the most
             recent sample will be considered for inclusion.

          -  Participants must have measurable or evaluable disease by RECIST version 1.1.

          -  Participants must agree to undergo a research biopsy, if tumor is safely accessible,
             at baseline. Participants for whom newly-obtained samples cannot be provided (e.g.
             inaccessible or participant safety concern) may submit an archived specimen. Tissue
             needs to be located and available at time of registration (See Section 9 for more
             details). Participants will be offered an optional repeat biopsy 3-6 weeks after
             starting treatment. For patients randomized to carboplatin alone who decide to
             crossover to nivolumab monotherapy at time of progression, a mandatory biopsy will be
             required if tumor is safely accessible for biopsy prior to initiating nivolumab;
             participants must also agree to undergo this biopsy, if applicable.

          -  Prior chemotherapy: Participants may have received 0-1 prior chemotherapeutic regimens
             for metastatic breast cancer and must have been off treatment with chemotherapy for at
             least 14 days prior to registration. No prior platinum in the metastatic setting is
             allowed. Prior platinum in the neo/adjuvant setting is permissible, if at least 12
             months elapsed since the end of adjuvant therapy to the development of metastatic
             disease. All toxicities related to prior chemotherapy must have resolved to CTCAE v4.0
             grade 1 or lower, unless otherwise specified in 3.1.10. If a patient recurs within 12
             months of neoadjuvant or adjuvant chemotherapy, this will be counted as one line of
             therapy for metastatic disease.

          -  Prior biologic therapy: Patients must have discontinued all biologic therapy at least
             14 days prior to registration. Prior poly-ADP ribose polymerase (PARP) inhibitors are
             allowed in the metastatic setting. Prior PARP inhibitors in the neo/adjuvant setting
             are permissible, if at least 12 months elapsed since the end of adjuvant therapy to
             the development of metastatic disease. All toxicities related to prior biologic
             therapy must have resolved to CTCAE v4.0 grade 1 or lower, unless otherwise specified
             in 3.1.10.

          -  Prior radiation therapy: Patients may have received prior radiation therapy. Radiation
             therapy must be completed at least 14 days prior to registration, and all toxicities
             related to prior radiation therapy must have resolved to CTCAE v4.0 grade 1 or lower,
             unless otherwise specified in 3.1.10. Patients may not have had >25% of their bone
             marrow radiated.

          -  The subject is ≥18 years old.

          -  ECOG performance status ≤1 (Karnofsky >60%, see Appendix A).

          -  Participants must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count ≥1,500/mcL

               -  Platelets ≥100,000/mcL

               -  Hemoglobin ≥ 9.0 g/dl

               -  Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (or ≤2.0 x ULN
                  in patients with documented Gilbert's Syndrome)

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or

                  ≤5 × institutional ULN for participants with documented liver metastases

               -  Serum creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 45 mL/min/
                  1.73m2 for participants with creatinine levels above institutional ULN.

          -  Supportive care (e.g. transfusion of red blood cells) is allowed to meet eligibility
             criteria.

          -  Female subjects of childbearing potential must have a negative serum or urine
             pregnancy test within 2 weeks prior to registration.

          -  Childbearing potential is defined as: participants who have not reached a
             postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause
             other than menopause) and have not undergone surgical sterilization (removal of
             ovaries and/or uterus).

          -  Women of childbearing potential (WOCBP) must agree to use an adequate method of
             contraception. Contraception is required starting with the first dose of study
             medication through 150 days (5 months) after the last dose of study medication.
             Examples of contraceptive methods with a failure rate of < 1% per year include
             bilateral tubal ligation, male sterilization, established and proper use of hormonal
             contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and
             copper intrauterine devices. Periodic abstinence (e.g., calendar, ovulation,
             symptothermal, or postovulation methods) and withdrawal are not acceptable methods of
             contraception.

          -  Males who are sexually active with WOCBP must agree to follow instructions for
             method(s) of contraception for the duration of study treatment with nivolumab and 7
             months after the last dose of study treatment (i.e., 90 days (duration of sperm
             turnover) plus the time required for the investigational drug to undergo approximately
             five half-lives.)

          -  Participants on bisphosphonates or RANK ligand inhibitors may continue receiving
             therapy during study treatment.

          -  The participant must be capable of understanding and complying with the protocol and
             willing to sign a written informed consent document

        Exclusion Criteria:

          -  Concurrent administration of any other anti-cancer therapy within 14 days of starting
             protocol therapy and during the course of this study (bisphosphonates and RANK ligand
             inhibitors are allowed).

          -  Prior hypersensitivity to platinum chemotherapy or to any of the excipients of
             platinum or nivolumab therapy.

          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic
             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including pembrolizumab,
             ipilimumab, and any other antibody or drug specifically targeting T-cell
             co-stimulation or checkpoint pathways).

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms. Participants with a history of treated central nervous system (CNS)
             metastases are eligible. Treated brain metastases are defined as those having no
             evidence of progression for ≥ 1 month after treatment, and no ongoing requirement for
             corticosteroids, as ascertained by clinical examination and brain imaging (magnetic
             resonance imaging or CT scan) completed during screening. Any corticosteroid use for
             brain metastases must have been discontinued without the subsequent appearance of
             symptoms for ≥2 weeks prior to registration. Treatment for brain metastases may
             include whole brain radiotherapy, radiosurgery, surgery or a combination as deemed
             appropriate by the treating physician.

          -  Major surgery within 2 weeks prior to registration. Patients must have recovered from
             any effects of any major surgery.

          -  Uncontrolled, significant intercurrent or recent illness including, but not limited
             to, ongoing or active infection, uncontrolled non-malignant systemic disease,
             uncontrolled seizures, or psychiatric illness/social situation that would limit
             compliance with study requirements in the opinion of the treating investigator.

          -  Participant has a medical condition that requires chronic systemic steroid therapy (>
             10 mg of prednisone daily or equivalent) or any other form of immunosuppressive
             medication (including disease modifying agents) and has required such therapy in the
             last 2 years. Replacement therapy (eg., thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic therapy.

          -  Participant has documented history of autoimmune disease or syndrome that currently
             requires systemic steroids or immunosuppressive agents.

          -  History or evidence of active, non-infectious pneumonitis or interstitial lung
             disease.

          -  Individuals with a history of a second malignancy are ineligible except for the
             following circumstances. Individuals with a history of other malignancies are eligible
             if they have been disease-free for at least 3 years or are deemed by the investigator
             to be at low risk for recurrence of that malignancy. Individuals with the following
             cancers that have been diagnosed and treated within the past 3 years are eligible:
             cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer
             of the skin. Patients with other cancers diagnosed within the past 3 years and felt to
             be at low risk of recurrence should be discussed with the study sponsor to determine
             eligibility.

          -  Participant is known to be positive for the human immunodeficiency virus (HIV),
             HepBsAg, or HCV RNA. HIV-positive participants are ineligible because of the potential
             for pharmacokinetic interactions of combination antiretroviral therapy with study
             drugs. In addition, these participants are at increased risk of fatal infections when
             treated with marrow-suppressive therapy.

          -  The participant has received a live vaccine within 28 days prior to registration.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. The
             use of the inactivated seasonal influenza vaccine is allowed.

          -  Women who are pregnant or breastfeeding or adults of reproductive potential not
             employing an adequate method of contraception.

          -  Childbearing potential is defined as: participants who have not reached a
             postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause
             other than menopause) and have not undergone surgical sterilization (removal of
             ovaries and/or uterus)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by progression-free survival (PFS), in patients with metastatic TNBC previously treated with 0 to 1 line of chemotherapy in the metastatic setting.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by overall response rate (ORR) according to RECIST 1.1 and immune-related response criteria (irRC), in patients with metastatic TNBC.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by overall survival (OS), in patients with metastatic TNBC.
Measure:Clinical Benefit Rate
Time Frame:2 years
Safety Issue:
Description:To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by clinical benefit rate (CBR) according to RECIST 1.1, in patients with metastatic TNBC.
Measure:Duration of Response
Time Frame:2 years
Safety Issue:
Description:To evaluate the duration of response (DOR) of carboplatin in combination with nivolumab versus carboplatin alone, in patients with metastatic TNBC.
Measure:Time to Objective Response
Time Frame:2 years
Safety Issue:
Description:To evaluate the time to objective response (TTOR) of carboplatin in combination with nivolumab versus carboplatin alone, in patients with metastatic TNBC.
Measure:BRCA carriers
Time Frame:2 years
Safety Issue:
Description:To explore the efficacy of carboplatin alone or in combination with nivolumab, as defined by progression free survival (PFS), for metastatic TNBC in patients with germline BRCA1 or BRCA2 mutations.
Measure:Incidence Rate of each Toxicity (safety and tolerability)
Time Frame:2 years
Safety Issue:
Description:To evaluate the safety and tolerability of carboplatin in combination with nivolumab, and compare to that of carboplatin alone, in patients with metastatic TNBC previously treated with 0 to 1 line of chemotherapy in the metastatic setting.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Breast Cancer

Last Updated

April 9, 2018