Vorinostat and Capecitabine in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT ID: NCT00121277

Last Updated: 2015-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as vorinostat and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat 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 vorinostat and capecitabine in treating patients with unresectable or metastatic solid tumors.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and recommended phase II dose of vorinostat (SAHA) and capecitabine in patients with metastatic or unresectable solid tumors.
• Determine the safety and tolerability of this regimen in these patients.

Secondary

• Correlate the clinical effects with the pharmacokinetic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral vorinostat (SAHA) once or twice daily and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses beyond documentation of CR. Patients achieving a partial response receive 2 courses beyond documentation of best response.

Cohorts of 3-6 patients receive escalating doses of SAHA and capecitabine 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. An additional 12 patients are treated at the MTD.

After completion of study treatment, patients are followed at 3-4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 18-30 patients will be accrued for this study within 6-10 months.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

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

Study Groups

SAHA (Suberoylanilide Acid) with Capecitabine

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

vorinostat

Intervention Type: DRUG

Interventions

capecitabine

Intervention Type: DRUG

vorinostat

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant solid tumor

• Metastatic or unresectable disease
• Standard curative or palliative measures do not exist or are no longer effective
• Patients who received prior radiotherapy must have measurable disease outside a previously irradiated field OR disease progression after prior radiotherapy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

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 ≤ 2.5 times upper limit normal (ULN)

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
• Able to swallow oral medication
• No clinical or radiological diagnosis of bowel obstruction
• No ongoing or active infection
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to suberoylanilide hydroxamic acid or other agents used in this study
• No known dihydropyrimidine dehydrogenase deficiency
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior fluorouracil allowed
• No prior capecitabine

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to > 40% of bone marrow

Surgery

• At least 4 weeks since prior surgery and recovered

Other

• At least 2 weeks since prior valproic acid
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric X. Chen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Hospital, Canada

Locations

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

CDR0000434850

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-6868

Identifier Type: -

Identifier Source: secondary_id

PMH-PHL-035

Identifier Type: -

Identifier Source: org_study_id