A Phase I Study of Suberoylanilide Hydroxamic Acid (Vorinostat) in Combination With 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX) in Patients With Colorectal Cancer and Other Solid Tumors
18 Years
N/A
Both
Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage III Colon Cancer, Stage III Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Suberoylanilide Hydroxamic Acid (Vorinostat) in Combination With 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX) in Patients With Colorectal Cancer and Other Solid Tumors
PRIMARY OBJECTIVES:
I. 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 OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. II. 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.
Inclusion Criteria:
- Histologically confirmed colorectal cancer
- Metastatic or unresectable disease OR diagnosis of solid tumor
- No known brain metastases
- ECOG 0-1 OR Karnofsky 70-100%
- Life expectancy > 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- WBC ≥ 3,000/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin normal
- AST and ALT ≤ 3 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- 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 psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- Prior bevacizumab and/or cetuximab allowed
- No concurrent routine or prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- More than 4 weeks since prior radiotherapy
- 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of vorinostat
Outcome Description:
Graded according to the NCI CTCAE.
Outcome Time Frame:
2 weeks
Safety Issue:
Yes
Principal Investigator
Marwan Fakih
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00083
NCT ID:
NCT00138177
Start Date:
July 2005
Completion Date:
Related Keywords:
- Recurrent Colon Cancer
- Recurrent Rectal Cancer
- Stage III Colon Cancer
- Stage III Rectal Cancer
- Stage IV Colon Cancer
- Stage IV Rectal Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- Colonic Neoplasms
- Rectal Neoplasms
- Colorectal Neoplasms
- Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
