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Carboplatin +/- Nivolumab in Metastatic Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT03414684
Recruitment Status : Recruiting
First Posted : January 30, 2018
Last Update Posted : October 2, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sara Tolaney, Dana-Farber Cancer Institute

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Carboplatin Drug: Nivolumab Phase 2

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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Carboplatin With or Without Nivolumab in First- or Second-line Metastatic Triple-negative Breast Cancer
Actual Study Start Date : January 30, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Carboplatin + Nivolumab
  • Nivolumab 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
Drug: Carboplatin
Carboplatin interferes with the development of the genetic material in a cell, which will cause the cancer cells to die.

Drug: Nivolumab
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 cells
Other Name: Opdivo

Experimental: Carboplatin
  • Carboplatin is administered every three weeks intravenously
  • Carboplatin dosage is pre-determined by the PI
Drug: Carboplatin
Carboplatin interferes with the development of the genetic material in a cell, which will cause the cancer cells to die.




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 2 years ]
    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 :
  1. Overall Response Rate [ Time Frame: 2 years ]
    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.

  2. Overall Survival [ Time Frame: 2 years ]
    To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by overall survival (OS), in patients with metastatic TNBC.

  3. Clinical Benefit Rate [ Time Frame: 2 years ]
    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.

  4. Duration of Response [ Time Frame: 2 years ]
    To evaluate the duration of response (DOR) of carboplatin in combination with nivolumab versus carboplatin alone, in patients with metastatic TNBC.

  5. Time to Objective Response [ Time Frame: 2 years ]
    To evaluate the time to objective response (TTOR) of carboplatin in combination with nivolumab versus carboplatin alone, in patients with metastatic TNBC.

  6. BRCA carriers [ Time Frame: 2 years ]
    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.

  7. Incidence Rate of each Toxicity (safety and tolerability) [ Time Frame: 2 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Previously collected archival tissue will also be obtained on all participants. For participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or participant safety concern) the archival tissue alone will be acceptable. Tissue needs to be located and availability confirmed at time of registration (See Section 9 for more details). Participants must agree to a mandatory repeat biopsy 3-6 weeks after starting treatment, if tumor is safely accessible. 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 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. 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03414684


Contacts
Contact: Paulina Lange 617-632-2257 paulinab_lange@dfci.harvard.edu

Locations
United States, Connecticut
The Stamford Hospital Recruiting
Stamford, Connecticut, United States, 06904
Contact: K.M. Steve Lo, MD       SLo@stamhealth.org   
Principal Investigator: K.M. Steve Lo, MD         
United States, Maine
Eastern Maine Medical Center Recruiting
Bangor, Maine, United States, 04401
Contact: Zarah F Lucas, MD       zdlucas@emhs.org   
Principal Investigator: Zarah F Lucas, MD         
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Nadine Tung, MD       ntung@bidmc.harvard.edu   
Principal Investigator: Nadine Tung, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Cassidy Elizabeth Kelley    617-632-3548    ckelley14@partners.org   
Principal Investigator: Sara Tolaney, MD         
St. Elizabeth's Medical Center Recruiting
Boston, Massachusetts, United States, 02135
Contact: caroline Block, MD       caroline_block@dfci.harvard.edu   
Principal Investigator: Caroline Block, MD         
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center Recruiting
Milford, Massachusetts, United States, 01757
Contact: Natalie Sinclair, MD       nsinclair1@partners.org   
Principal Investigator: Natalie Sinclair, MD         
Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital Recruiting
South Weymouth, Massachusetts, United States, 02190
Contact: Dorcas Chi, MD       dorcas_chi@dfci.harvard.edu   
Principal Investigator: Dorcas Chi, MD         
United States, New Hampshire
Dana-Farber/New Hampshire Oncology-Hematology Recruiting
Londonderry, New Hampshire, United States, 03053
Contact: Fred Briccetti, MD       fred_briccetti@dfci.harvard.edu   
Principal Investigator: Fred Briccetti, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Robert Wesolowski, MD       robert.wesolowski@osumc.edu   
Principal Investigator: Robert Wesolowski, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: Sara Tolaney, MD Dana-Farber Cancer Institute

Responsible Party: Sara Tolaney, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03414684     History of Changes
Other Study ID Numbers: 17-512
CA209-9JX ( Other Identifier: Bristol-Myers Squibb )
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: October 2, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sara Tolaney, Dana-Farber Cancer Institute:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Nivolumab
Carboplatin
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs