Phase I Study of CS-7017 and Bexarotene

Phase 1

Terminated

• Conditions: Lymphoma; Solid Tumors; Multiple Myeloma
• Interventions: Drug: CS-7017 and Bexarotene

• Registration Number: NCT01504490
• Lead Sponsor: Georgetown University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2011-12-14
• Study First Submitted QC: 2012-01-03
• Study First Posted: 2012-01-05
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-13
• Last Update Posted: 2017-02-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CS-7017 and Bexarotene	CS-7017 and Bexarotene	Combination of CS-7017 and Bexarotene

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	12 months	The highest dose at which \< 1 out of 6 subjects experienced a dose-limiting toxicity

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Georgetown Lombardi Comprehensive Cancer Center; 🇺🇸 Washington, District of Columbia, United States