Phase I Study of CS-7017 and Bexarotene
Primary Purpose
Solid Tumors, Lymphoma, Multiple Myeloma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CS-7017 and Bexarotene
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumors focused on measuring Advanced cancer
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)
Sites / Locations
- Georgetown Lombardi Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CS-7017 and Bexarotene
Arm Description
Combination of CS-7017 and Bexarotene
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose
The highest dose at which < 1 out of 6 subjects experienced a dose-limiting toxicity
Secondary Outcome Measures
Response rate
Complete response + partial response
Disease control rate
Response rate + stable disease
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.
Pharmacokinetics
Trough serum levels of CS-7017 and its metabolites
Full Information
NCT ID
NCT01504490
First Posted
December 14, 2011
Last Updated
February 13, 2017
Sponsor
Georgetown University
Collaborators
Daiichi Sankyo, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01504490
Brief Title
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
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
Drug no longer available
Study Start Date
December 2011 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
Daiichi Sankyo, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Lymphoma, Multiple Myeloma
Keywords
Advanced cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CS-7017 and Bexarotene
Arm Type
Experimental
Arm Description
Combination of CS-7017 and Bexarotene
Intervention Type
Drug
Intervention Name(s)
CS-7017 and Bexarotene
Other Intervention Name(s)
Efatutazone, Targretin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
The highest dose at which < 1 out of 6 subjects experienced a dose-limiting toxicity
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Response rate
Description
Complete response + partial response
Time Frame
4 months
Title
Disease control rate
Description
Response rate + stable disease
Time Frame
4 months
Title
Pharmacodynamic effects
Description
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.
Time Frame
Prior to treatment, Just prior to Day 1 and just prior to Day 15 of cycle 1
Title
Pharmacokinetics
Description
Trough serum levels of CS-7017 and its metabolites
Time Frame
Day -7 prior to first dose of CS-7017, Day 1, and Day 15 of Cycle 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Pishvaian, MD PhD
Organizational Affiliation
Georgetown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase I Study of CS-7017 and Bexarotene
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