Suberoylanilide Hydroxamic Acid, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Progressive Metastatic or Unresectable Colorectal Cancer or Other Solid Tumors

NCT ID: NCT00138177

Last Updated: 2013-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31

Brief Summary

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. 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.

Detailed Description

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (vorinostat, mFOLFOX)

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.

Group Type: EXPERIMENTAL

oxaliplatin

Intervention Type: DRUG

Given IV

leucovorin calcium

Intervention Type: DRUG

Given IV

vorinostat

Intervention Type: DRUG

Given orally

fluorouracil

Intervention Type: DRUG

Given IV

Interventions

oxaliplatin

Given IV

Intervention Type: DRUG

leucovorin calcium

Given IV

Intervention Type: DRUG

vorinostat

Given orally

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

Other Intervention Names

1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP; CF; CFR; LV; L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; 5-fluorouracil; 5-Fluracil; 5-FU

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marwan Fakih

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

Other Identifiers

NCI-2009-00083

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000439445

Identifier Type: -

Identifier Source: secondary_id

I 55305

Identifier Type: OTHER

Identifier Source: secondary_id

6789

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00083

Identifier Type: -

Identifier Source: org_study_id