Phase I Study of CS-7017 and Bexarotene

A Phase I Study of a Combination of the Proteosome Proliferator-Activated Receptor Gamma Agonist, CS-7017 and the Retinoid X Receptor Agonist, Bexarotene

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma; Multiple Myeloma; Solid Tumors
• Intervention / Treatment: Drug: CS-7017 and Bexarotene

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Lombardi Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Targretin; Efatutazone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	The highest dose at which < 1 out of 6 subjects experienced a dose-limiting toxicity	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Complete response + partial response	4 months
Disease control rate	Response rate + stable disease	4 months
Pharmacodynamic effects	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.	Prior to treatment, Just prior to Day 1 and just prior to Day 15 of cycle 1
Pharmacokinetics	Trough serum levels of CS-7017 and its metabolites	Day -7 prior to first dose of CS-7017, Day 1, and Day 15 of Cycle 1

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: December 14, 2011
• First Submitted That Met QC Criteria: January 3, 2012
• First Posted (Estimate): January 5, 2012

Study Record Updates

• Last Update Posted (Actual): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Advanced cancer
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Multiple Myeloma; Antineoplastic Agents; Bexarotene; Efatutazone
• Other Study ID Numbers: 2011-345