Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
Study combination use of cisplatin plus romidepsin and nivolumab in metastatic triple negative breast cancer (TNBC) or BRCA mutation-associated locally recurrent or metastatic breast cancer
Full description
Breast cancer is the most common cancer and the second leading cause of cancer related death in American women. Despite recent improvement in the treatment of breast cancer, 40,000 women per year still die in the U.S.as a result of breast cancer. Once the disease has gotten worse (progressed) after standard chemotherapy treatments, there are limited treatment options and the likelihood for patients to recover is very small.
The study will be done in two phases:
Phase I will determine the highest dose of romidepsin that is safe and tolerable to take in combination with cisplatin.
Phase II will determine if taking romidepsin (at the dose determined in Phase I) in combination with cisplatin and nivolumab is safe and effective in treating patients with breast cancer.
Phase I will complete before Phase II begins.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Subjects must meet at least one of the following two criteria:
Breast cancer that is either stage III disease not amenable to curative therapy or stage IV
Have at least one measurable lesion of ≥ 2 cm by conventional methods or ≥ 1 cm on spiral CT
No limit to prior therapy for metastatic breast cancer. Prior treatment with cisplatin is excluded, unless prior cisplatin treatment was given in the neo/adjuvant setting. All other platinum compounds are allowed as long as it has been 6 months since last platinum exposure.
All patients should have received at least one line of chemotherapy in either the advanced or adjuvant setting and hormonal therapy (where appropriate). Participants who have previously been treated with endocrine therapy only, and later develop triple negative disease are eligible as long as they have had one line of chemotherapy in either the advanced or adjuvant setting.
Eastern Oncology Cooperative Group (ECOG) Performance status of ≥ 2
Laboratory values as follows:
IV bisphosphonate and denosumab for bony metastatic disease is allowed
Radiation to bony metastases is allowed ≥ 14 days before starting study treatment
Subjects with previously treated brain metastasis who are free of central nervous system (CNS) symptoms and are ≥ 14 days from treatment of brain metastasis are eligible.
Women of child bearing potential and their partners must use contraception prior to study entry, continuing for 5 months after treatment.
Exclusion criteria
Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, biologic, targeted therapy, or any investigational therapy within either 14 days or 5 half-lives (whichever is shorter), prior to study drug administration.
Subjects who have not recovered to within one grade level (not to exceed Grade 2) of their baseline following a significant adverse event or toxicity attributed to prior treatment.
Other medical or psychiatric disorder placing the subject at undue risk for treatment complications
Subject is pregnant or lactating
Subject has previously been treated with a Histone deacetylases (HDAC) inhibitor, PD-1 inhibitor, PD-L1 inhibitor, PD-L2 inhibitor, CTLA-4 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
Subject tests positive for hepatitis B or C indicating acute or chronic infection
Subject has known history of testing positive for HIV or AIDS
Subject has inflammatory breast cancer
Subject has a known hypersensitivity to any of the excipients of nivolumab, cisplatin or romidepsin
Subject has a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer or prior ovarian/breast cancer in patients with BRCA associated breast cancer).
Subject is classified into Child-Pugh Class C
Subject has active, uncontrolled infection
Subject has symptomatic/untreated CNS disease
Subject has an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
Subject has active cardiac disease or a history of cardiac dysfunction, including:
Subject has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
Subject is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug or who have not fully recovered from side effects of such treatment. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
Subject is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The subject must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the start of treatment.
Subject is currently receiving warfarin or other coumarin derived anti-coagulant for treatment. Therapy with heparin, low molecular weight heparin (LMWH), Factor Xa or fondaparinux is allowed.
Subjects with baseline peripheral neuropathy that exceeds Grade 1.
Primary purpose
Allocation
Interventional model
Masking
51 participants in 4 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal