Vorinostat and Capecitabine in Treating Patients With Metastatic or Unresectable Solid Tumors
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Unspecified Adult Solid Tumor, Protocol Specific |
Drug: capecitabine Drug: vorinostat |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Capecitabine in Patients With Solid Tumors |
- Maximum tolerated doses of vorinostat (SAHA) and capecitabine [ Designated as safety issue: Yes ]
- Safety and tolerability as assessed by CTCAE v3.0 [ Designated as safety issue: Yes ]
- Response rate as assessed by RECIST criteria [ Designated as safety issue: No ]
- Molecular markers as assessed by molecular analysis [ Designated as safety issue: No ]
- Survival [ Designated as safety issue: No ]
| Estimated Enrollment: | 30 |
| Study Start Date: | September 2005 |
| Primary Completion Date: | August 2009 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Canada, Ontario | |
| Ottawa Hospital Regional Cancer Centre - General Campus | |
| Ottawa, Ontario, Canada, K1H 8L6 | |
| Princess Margaret Hospital | |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Principal Investigator: | Eric X. Chen, MD, PhD | Princess Margaret Hospital, Canada |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00121277 History of Changes |
| Other Study ID Numbers: | CDR0000434850, PMH-PHL-035, NCI-6868 |
| Study First Received: | July 19, 2005 |
| Last Updated: | August 24, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
unspecified adult solid tumor, protocol specific |
Additional relevant MeSH terms:
|
Neoplasms Capecitabine Fluorouracil Vorinostat Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Histone Deacetylase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013