Phase I Study of CS-7017 and Bexarotene

This study is currently recruiting participants.
Verified February 2014 by Georgetown University
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT01504490
First received: December 14, 2011
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

This study is for patients with advanced solid tumors. The purpose of this study is to test the safety and effectiveness of a new combination of drugs, CS-7017 and Bexarotene in patients with advanced cancer. CS-7017 and Bexarotene both have many effects on cancer cells, including stopping cancer cells from growing and dividing, and causing the cancer cells to die. CS-7017 and Bexarotene work on cancer cells in a similar manner and both drugs together may have an even greater effect against cancer cells, hopefully, increasing the killing of cancer cells.

CS-7017 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in any type of cancer. Bexarotene is an anti-cancer agent that has been approved by the FDA for patients with a specific type of cancer, cutaneous T-cell lymphoma.

This study will help find out what effects the combination of drugs, CS-7017 and Bexarotene, has on cancer. This research is being done because it is not known if CS-7017 is safe to be given with Bexarotene.


Condition Intervention Phase
Solid Tumors
Lymphoma
Multiple Myeloma
Drug: CS-7017 and Bexarotene
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of a Combination of the Proteosome Proliferator-Activated Receptor Gamma Agonist, CS-7017 and the Retinoid X Receptor Agonist, Bexarotene

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The highest dose at which < 1 out of 6 subjects experienced a dose-limiting toxicity


Secondary Outcome Measures:
  • Response rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Complete response + partial response

  • Disease control rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Response rate + stable disease

  • Pharmacodynamic effects [ Time Frame: Prior to treatment, Just prior to Day 1 and just prior to Day 15 of cycle 1 ] [ Designated as safety issue: No ]
    PPAR-gamma and RXR analysis by immunohistochemistry; Tumor staining for the following PPAR-gamma regulated genes: Cyclin D1, p16, p18, p21, p27, and c-myc.

  • Pharmacokinetics [ Time Frame: Day -7 prior to first dose of CS-7017, Day 1, and Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
    Trough serum levels of CS-7017 and its metabolites


Estimated Enrollment: 22
Study Start Date: December 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CS-7017 and Bexarotene
Combination of CS-7017 and Bexarotene
Drug: CS-7017 and Bexarotene

CS-7017 will be administered orally, twice daily for 28 days of each 28-day cycle in escalating doses depending on cohort patient is assigned to.

Bexarotene will be administered orally once daily for 28 days of each 28-day cycle. The dose a patient receives will depend on which cohort the patient is assigned to.

Other Names:
  • Efatutazone
  • Targretin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven advanced malignancy with measurable disease except for acute leukemias
  • Progression on, or intolerance of, or ineligibility for all standard therapies
  • Biopsy accessible tumor deposits
  • Tumor expression of PPAR-gamma, RXR or both
  • LVEF >/= institutional normal
  • No evidence of clinically significant fluid retention
  • ECOG Performance status 0-2
  • Subjects with no brain metastases or a history of previously treated brain metastases who have been treated with surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of intracranial disease and have not had treatment with steroids within one week of study enrollment.
  • Adequate hepatic, bone marrow, and renal function
  • Partial thromboplastin time must be </= 1.5 x upper limit of normal range and INR < 1.5. Subjects on anticoagulant will be permitted to enroll as long as the INR is in the acceptable therapeutic range
  • Life expectancy > 12 weeks
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • Subject is capable of understanding and complying with parameters of the protocol and able to sign and date the informed consent.

Exclusion Criteria:

  • Prior CS-7017 treatment
  • Treatment with thiazolidinediones (TZDs) within 4 weeks prior to start of study treatment
  • Current need for concomitant use of other TZDs during the study
  • Grade 2 or greater fasting hypertriglyceridemia
  • Concurrent use of insulin
  • Concurrent use of known CYP 3A4 inhibiting or activating medications
  • CNS metastases which do not meet the criteria outlines in inclusion criteria
  • Active severe infection or known chronic infection with HIV or hepatitis B virus
  • Cardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke or congestive heart failure within the last 6 months
  • Life-threatening visceral disease or other severe concurrent disease
  • Women who are pregnant or breastfeeding
  • Anticipated survival under 3 months
  • Clinically significant and uncontrolled major medical condition(s)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01504490

Contacts
Contact: Ion Cotarla 202-687-4510 ic34@georgetown.edu
Contact: Christine Fasano, RN 202-687-2007 ccf42@georgetown.edu

Locations
United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Ion Cotarla    202-687-4510    ic34@georgetown.edu   
Contact: Christine Fasano, RN    202-687-2007    ccf42@georgetown.edu   
Principal Investigator: Michael Pishvaian, MD PhD         
Sponsors and Collaborators
Georgetown University
Daiichi Sankyo Inc.
Investigators
Principal Investigator: Michael Pishvaian, MD PhD Georgetown University
  More Information

No publications provided

Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT01504490     History of Changes
Other Study ID Numbers: 2011-345
Study First Received: December 14, 2011
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
Advanced cancer

Additional relevant MeSH terms:
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bexarotene
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014