Clinical trial NCT01504490: Phase I Study of CS-7017 and Bexarotene
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Lymphoma
Multiple Myeloma
Keywords: Advanced cancer
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo
First posted: 2012-01-05
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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
* 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)

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 12 months
Secondary outcomes:
measure: Response rate
timeFrame: 4 months
measure: Disease control rate
timeFrame: 4 months
measure: Pharmacodynamic effects
timeFrame: Prior to treatment, Just prior to Day 1 and just prior to Day 15 of cycle 1
measure: Pharmacokinetics
timeFrame: Day -7 prior to first dose of CS-7017, Day 1, and Day 15 of Cycle 1
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown Lombardi Comprehensive Cancer Center
state: District of Columbia
Study officials:
affiliation: Georgetown University
name: Michael Pishvaian, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: