Cisplatin Plus Romidepsin & Nivolumab in Locally Recurrent or Metastatic Triple Negative Breast Cancer (TNBC)

NCT02393794 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: IIT-2014-CISRomiNivoTNBCRM-CL-BRST-PI-002783IIT-2014-PS-BRST-CISRomiTNBC
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Triple-Negative Breast Cancer; Breast Cancer

Keywords

BRCA1; BRCA2; TNBC

Outcome Measures

Primary Outcomes (2)

• Phase I: Recommended Phase II Dose of romidepsin in combination with cisplatin

  12 months

• Phase II: Objective response rate of treated subjects according to RECIST v1.1 criteria

  24 months

Secondary Outcomes (4)

• Phase II: Clinical Benefit Rate at 16 weeks of study treatment for subjects treated at the recommended phase II dose of romidepsin plus cisplatin and nivolumab

  24 months

• Pharmacokinetics - romidepsin plasma concentration vs time profile when given with cisplatin and nivolumab

  12 months

• Pharmacokinetics - cisplatin plasma concentration vs time profile when given with romidepsin

  12 months

• Median Progression-Free Survival and Overall Survival

  36 months

Study Arms (4)

Romidepsin (8mg/m2) + Cisplatin (75mg/m2)

EXPERIMENTAL

Romidepsin 8mg/m2 IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle

Drug: Romidepsin; Drug: Cisplatin

Romidepsin (10mg/m2) + Cisplatin (75mg/m2)

EXPERIMENTAL

Romidepsin 10mg/m2 IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle

Drug: Romidepsin; Drug: Cisplatin

Romidepsin (12mg/m2) + Cisplatin (75mg/m2)

EXPERIMENTAL

Romidepsin 12mg/m2 IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle

Drug: Romidepsin; Drug: Cisplatin

Romidepsin Dose Expansion

EXPERIMENTAL

Romidepsin maximum tolerated dose (MTD) from Phase I IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle Nivolumab 360mg on day 1 of each 21 day cycle

Drug: Romidepsin; Drug: Cisplatin; Drug: Nivolumab

Interventions

Romidepsin DRUG

Histone deacetylase inhibitor

Also known as: Histone deacetylase inhibitor

Romidepsin (10mg/m2) + Cisplatin (75mg/m2); Romidepsin (12mg/m2) + Cisplatin (75mg/m2); Romidepsin (8mg/m2) + Cisplatin (75mg/m2); Romidepsin Dose Expansion

Cisplatin DRUG

Platinum compound

Also known as: Platinol

Romidepsin (10mg/m2) + Cisplatin (75mg/m2); Romidepsin (12mg/m2) + Cisplatin (75mg/m2); Romidepsin (8mg/m2) + Cisplatin (75mg/m2); Romidepsin Dose Expansion

Nivolumab DRUG

Monoclonal antibody, checkpoint inhibitor

Also known as: Opdivo

Romidepsin Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet at least one of the following two criteria:
• Histologically proven TNBC
• Confirmed germline BRCA1 or BRCA2 mutation, regardless of subtype of breast cancer
• 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:
• absolute neutrophil count ≥ 1,500/uL (microliter)
• platelets ≥ 100,000/uL (no transfusion allowed within 2 weeks)
• hemoglobin \> 9 g/dL (which may be reached by transfusion)
• total bilirubin within normal range or ≤ 1.5 x IULN (Institutional Upper Limit of Normal) if liver metastases
• total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in subjects with Gilbert's Syndrome
• aspartate aminotransferase (AST) (SGOT) /Alanine transaminase (ALT) (SPGT) ≤ 2.5 x IULN or ≤ 5 x IULN if liver metastases

You may not qualify if:

• 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:

Sponsors & Collaborators

• Priyanka Sharma: lead
• Celgene Corporation: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (7)

University of Kansas Cancer Center - Clinical Research Center

Fairway, Kansas, 66205, United States

Location

University of Kansas Cancer Center - West

Kansas City, Kansas, 66112, United States

Location

University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, 66210, United States

Location

University of Kansas Cancer Center - Westwood

Westwood, Kansas, 66205, United States

Location

University of Kansas Cancer Center - South

Kansas City, Missouri, 64131, United States

Location

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

romidepsin; Histone Deacetylase Inhibitors; Cisplatin; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Priyanka Sharma, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 13, 2015
• First Posted: March 19, 2015
• Study Start: July 17, 2015
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)