Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	18 and over	NCI	RPCI-I 55305 6789, I 55305, NCI-6789, NCT00138177

Objectives

Primary

1. 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

1. Determine the toxicity of this regimen in these patients.
2. Determine the pharmacokinetics of oxaliplatin, fluorouracil, and suberoylanilide hydroxamic acid in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed colorectal cancer
  • Metastatic or unresectable disease

  OR

• Diagnosis of solid tumor
• No known brain metastases

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

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/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

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

Expected Enrollment

A total of 54 patients will be accrued for this study.

Outcomes

Maximum tolerated dose

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.

Fakih MG, Pendyala L, Fetterly G, et al.: A phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory colorectal cancer. Clin Cancer Res 15 (9): 3189-95, 2009.[PUBMED Abstract]

Fakih MG, Pendyala L, Smith P, et al.: A phase I study of vorinostat (suberoylanilide hydroxamic acid) in combination with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in patients with advanced colorectal cancer (CRC). [Abstract] J Clin Oncol 25 (Suppl 18): A-4088, 185s, 2007.

Trial Contact Information

Trial Lead Organizations

Roswell Park Cancer Institute

Marwan Fakih, MD, Protocol chair		Ph: 716-845-3362; 800-685-6825 Email: marwan.fakih@roswellpark.org

U.S.A.
New York
	Buffalo
	Roswell Park Cancer Institute
		Marwan Fakih, MD	Ph:  716-845-3362
			Email: marwan.fakih@roswellpark.org

Registry Information
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
Trial Start Date		2005-07-05
Trial Completion Date		2009-06-02 (estimated)
Registered in ClinicalTrials.gov		NCT00138177
Date Submitted to PDQ		2005-06-29
Information Last Verified		2009-07-06
NCI Grant/Contract Number		CA16056

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