Phase I Study of CS-7017 and Bexarotene
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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:
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Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose [12 months]
The highest dose at which < 1 out of 6 subjects experienced a dose-limiting toxicity
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically proven advanced malignancy with measurable disease except for acute leukemias
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Progression on, or intolerance of, or ineligibility for all standard therapies
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Biopsy accessible tumor deposits
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LVEF >/= institutional normal
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No evidence of clinically significant fluid retention
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ECOG Performance status 0-2
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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.
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Adequate hepatic, bone marrow, and renal function
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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
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Life expectancy > 12 weeks
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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.
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Subject is capable of understanding and complying with parameters of the protocol and able to sign and date the informed consent.
Exclusion Criteria:
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Prior CS-7017 treatment
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Treatment with thiazolidinediones (TZDs) within 4 weeks prior to start of study treatment
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Current need for concomitant use of other TZDs during the study
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Grade 2 or greater fasting hypertriglyceridemia
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Concurrent use of insulin
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Concurrent use of known CYP 3A4 inhibiting or activating medications
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CNS metastases which do not meet the criteria outlines in inclusion criteria
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Active severe infection or known chronic infection with HIV or hepatitis B virus
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Cardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke or congestive heart failure within the last 6 months
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Life-threatening visceral disease or other severe concurrent disease
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Women who are pregnant or breastfeeding
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Anticipated survival under 3 months
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Clinically significant and uncontrolled major medical condition(s)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Georgetown Lombardi Comprehensive Cancer Center | Washington | District of Columbia | United States | 20007 |
Sponsors and Collaborators
- Georgetown University
- Daiichi Sankyo, Inc.
Investigators
- Principal Investigator: Michael Pishvaian, MD PhD, Georgetown University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2011-345