Suberoylanilide Hydroxamic Acid, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Progressive Metastatic or Unresectable Colorectal Cancer or Other Solid Tumors
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Colorectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific
Intervention: fluorouracil (Drug); leucovorin calcium (Drug); oxaliplatin (Drug); vorinostat (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: Roswell Park Cancer Institute Official(s) and/or principal investigator(s):
Marwan Fakih, MD, Study Chair, Affiliation: Roswell Park Cancer Institute
Summary
RATIONALE: Drugs used in chemotherapy, such as suberoylanilide hydroxamic acid,
fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of
tumor cells, either by killing the cells or by stopping them from dividing. Suberoylanilide
hydroxamic acid may also stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth. Giving more than one drug (combination chemotherapy) may kill more
tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of suberoylanilide
hydroxamic acid when given together with fluorouracil, leucovorin, and oxaliplatin in
treating patients with progressive metastatic or unresectable colorectal cancer or solid
tumor.
Clinical Details
Official title: A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With 5-Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) in Patients With Advanced Colorectal Cancer or Other Solid Tumors
Study design: Treatment
Primary outcome: Maximum tolerated dose
Detailed description:
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of suberoylanilide hydroxamic acid when
administered with fluorouracil, leucovorin calcium, and oxaliplatin in patients with
progressive metastatic or unresectable colorectal cancer or other solid tumors.
Secondary
- Determine the toxicity of this regimen in these patients.
- Determine the pharmacokinetics of oxaliplatin, fluorouracil, and suberoylanilide
hydroxamic acid in these patients.
OUTLINE: This is a dose-escalation study of suberoylanilide hydroxamic acid (SAHA).
Patients receive oral SAHA once or twice daily on days 1-3. Patients also receive
oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 4 followed by
fluorouracil IV over 46 hours on days 4-5. Courses repeat every 14 days in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed for 4 weeks.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed colorectal cancer
- Metastatic or unresectable disease OR
- Diagnosis of solid tumor
- No known brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1 OR
- Karnofsky 70-100%
Life expectancy
- More than 12 weeks
Hematopoietic
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin normal
- AST and ALT ≤ 3 times upper limit of normal
Renal
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
participation
- No ongoing or active infection
- No neuropathy > grade 1
- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to study drugs
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior bevacizumab and/or cetuximab allowed
- No concurrent routine or prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
Chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
Endocrine therapy
- Not specified
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- Not specified
Other
- Recovered from prior therapy
- At least 2 weeks since prior valproic acid
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Locations and Contacts
Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States; Recruiting
Marwan Fakih, MD, Phone: 716-845-3362, Email: marwan.fakih@roswellpark.org
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: July 2005
Last updated: September 17, 2009
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