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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00121277
First received: July 19, 2005
Last updated: August 24, 2012
Last verified: October 2007
  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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121277

Locations
Canada, Ontario
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Princess Margaret Hospital, Canada
Investigators
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 July 20, 2014