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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by University of Kansas Medical Center
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Priyanka Sharma, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier:
NCT02393794
First received: March 13, 2015
Last updated: August 18, 2016
Last verified: August 2016
  Purpose
Investigate the use of romidepsin as combination therapy with cisplatin in locally recurrent or metastatic triple negative breast cancer or BRCA1 or BRCA2 mutation associated locally recurrent or metastatic breast cancer.

Condition Intervention Phase
Triple-Negative Breast Cancer
Breast Cancer
Drug: Romidepsin
Drug: Cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Cisplatin Plus Romidepsin in Locally Recurrent or Metastatic Triple Negative Breast Cancer or BRCA1 or BRCA2 Mutation Associated Locally Recurrent or Metastatic Breast Cancer.

Resource links provided by NLM:


Further study details as provided by University of Kansas Medical Center:

Primary Outcome Measures:
  • Phase I: Recommended Phase II Dose of romidepsin + cisplatin to be used in combination therapy of advanced triple negative breast cancer [ Time Frame: 12 months ]
  • Phase II: Overall Response Rate of subjects treated at the recommended phase II dose. [ Time Frame: 24 months ]

Secondary Outcome Measures:
  • Clinical Benefit Rate at 16 weeks of study treatment for subjects treated at the recommended phase II dose [ Time Frame: 24 months ]
  • Pharmacokinetics - romidepsin plasma concentration vs time profile when given with cisplatin [ Time Frame: 12 months ]
  • Pharmacokinetics - cisplatin plasma concentration vs time profile when given with romidepsin [ Time Frame: 12 months ]
  • Progression-Free Survival and Overall Survival [ Time Frame: 36 months ]

Estimated Enrollment: 54
Study Start Date: July 2015
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Romidepsin (8mg/m2) + Cisplatin (75mg/m2)
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
Histone deacetylase inhibitor
Other Name: Histone deacetylase inhibitor
Drug: Cisplatin
Platinum compound
Other Name: Platinol
Experimental: Romidepsin (10mg/m2) + Cisplatin (75mg/m2)
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
Histone deacetylase inhibitor
Other Name: Histone deacetylase inhibitor
Drug: Cisplatin
Platinum compound
Other Name: Platinol
Experimental: Romidepsin (12mg/m2) + Cisplatin (75mg/m2)
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
Histone deacetylase inhibitor
Other Name: Histone deacetylase inhibitor
Drug: Cisplatin
Platinum compound
Other Name: Platinol
Experimental: Romidepsin Dose Expansion
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
Drug: Romidepsin
Histone deacetylase inhibitor
Other Name: Histone deacetylase inhibitor
Drug: Cisplatin
Platinum compound
Other Name: Platinol

Detailed 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 purpose of this study is to determine the highest dose of romidepsin combined with cisplatin that results in no serious side effects. The safety and efficacy of romidepsin combined with cisplatin will be assessed, along with the determination of how long this drug combination will keep the disease from getting worse.

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 is safe and effective in treating patients with breast cancer.

Phase I will complete before Phase II begins.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must meet at least one of the following two criteria:

    1. Histologically proven TNBC
    2. 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 if liver metastases
    • total bilirubin ≤ 3.0 x IULN (Institutional Upper Limit of Normal) 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
    • Serum creatinine ≤ 1.5 x IULN
    • International Normalized Ration (INR) ≤ 1.5
    • Serum potassium > 3.8 mmol/L
    • Serum magnesium >1.8 mg/dL
  • 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 weeks 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
  • Subject has inflammatory breast cancer
  • Subject has a known hypersensitivity to 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 a known history of HIV, Hepatitis B or Hepatitis C infection (testing is not mandatory)
  • Subject has active, uncontrolled infection
  • Subject has symptomatic/untreated CNS disease
  • Subject has active or a history of cardiac disease including:

    • Congenital long QT syndrome
    • Corrected QT interval (QTc) interval ≥ 500 ms on the screening ECG (using the corrected QT interval to Fridericia's formula [QTcF])
    • Myocardial infarction within 6 months of Cycle 1 Day 1 (C1D1).
    • Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
    • Symptomatic coronary artery disease (CAD)
    • An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥ 2 mm, measured from isoelectric line to the ST segment).
    • Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction < 40% by Multi Gated Acquisition Scan (MUGA) or < 50% by echocardiogram and/or MRI
    • A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
    • Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
    • Uncontrolled hypertension, i.e., blood pressure (BP) of ≥ 160/95; subjects who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria
    • Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
    • Subjects taking drugs leading to significant QT prolongation
    • Concomitant use of CYP3A4 inhibitors
  • 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
  • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02393794

Contacts
Contact: Priyanka Sharma, MD 913-588-6029 psharma2@kumc.edu
Contact: Kerry Hepler 913-945-7552 khepler@kumc.edu

Locations
United States, Kansas
University of Kansas Cancer Center - Clinical Research Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Priyanka Sharma, MD    913-588-6029    psharma2@kumc.edu   
Contact: Kerry Hepler    913-945-7552    khepler@kumc.edu   
University of Kansas Cancer Center - West Not yet recruiting
Kansas City, Kansas, United States, 66112
Contact: Kristina Pringle    913-574-2626    ksharpe-pringle@kumc.edu   
University of Kansas Cancer Center - Overland Park Not yet recruiting
Overland Park, Kansas, United States, 66210
Contact: Valerie Francis    913-574-2672    vfrancis@kumc.edu   
University of Kansas Cancer Center - Westwood Not yet recruiting
Westwood, Kansas, United States, 66205
Contact: Priyanka Sharma, MD    913-588-6029      
Contact: Kerry Hepler    913-945-7552    khepler@kumc.edu   
United States, Missouri
University of Kansas Cancer Center - South Not yet recruiting
Kansas City, Missouri, United States, 64131
Contact    913-574-2490      
University of Kansas Cancer Center - North Not yet recruiting
Kansas City, Missouri, United States, 64154
Contact: Jessica Slover, MD    913-574-2560    jslover@kumc.edu   
University of Kansas Cancer Center - Lee's Summit Not yet recruiting
Lee's Summit, Missouri, United States, 64064
Contact: Jan Ward    913-574-2372    jward3@kumc.edu   
Sponsors and Collaborators
Priyanka Sharma
Celgene Corporation
Investigators
Principal Investigator: Priyanka Sharma, MD University of Kansas
  More Information

Responsible Party: Priyanka Sharma, Associate Professor, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier: NCT02393794     History of Changes
Other Study ID Numbers: IIT-2014-PS-BRST-CISRomiTNBC
RM-CL-BRST-PI-002783 ( Other Identifier: Celgene )
Study First Received: March 13, 2015
Last Updated: August 18, 2016

Keywords provided by University of Kansas Medical Center:
BRCA1
BRCA2
TNBC

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Romidepsin
Cisplatin
Histone Deacetylase Inhibitors
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on April 26, 2017