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Suberoylanilide Hydroxamic Acid in Treating Patients With Advanced Cancer

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ClinicalTrials.gov Identifier: NCT00045006
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : May 30, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE September 6, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date May 30, 2013
Study Start Date  ICMJE July 2001
Actual Primary Completion Date December 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00045006 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Suberoylanilide Hydroxamic Acid in Treating Patients With Advanced Cancer
Official Title  ICMJE Phase I Clinical Trial of Oral Suberoylanilide Hydroxamic Acid - SAHA (MSK390) in Patients With Advanced Solid Tumors and Hematologic Malignancies
Brief Summary

RATIONALE: Suberoylanilide hydroxamic acid may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I trial to study the effectiveness of suberoylanilide hydroxamic acid in treating patients who have advanced cancer.

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of suberoylanilide hydroxamic acid in patients with advanced solid tumors or hematologic malignancies.
  • Evaluate the pharmacokinetic profile of this drug in these patients.
  • Determine the effects of this drug on absorption in the fasting and non-fasting states in these patients.
  • Determine any anti-tumor effects of this drug in these patients.
  • Correlate clinical outcomes with histone acetylation in circulating mononuclear cells and tumor biopsy samples in patients treated with this drug.

OUTLINE: This is a dose-escalation study. Patients are stratified according to disease (solid tumor vs multiple myeloma or lymphoma vs leukemia or myelodysplastic syndromes).

The initial 15-20 patients (in the solid tumor or multiple myeloma or lymphoma stratum) receive suberoylanilide hydroxamic acid (SAHA) IV over 2 hours on day 1 of week 0 and then orally once or twice daily beginning on day 1 of week 1. All remaining patients receive oral SAHA once or twice daily beginning on day 1 of week 1. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

In each stratum, 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed monthly for resolution of adverse events.

PROJECTED ACCRUAL: A maximum of 114 patients (42 with solid tumors, 36 with lymphoma or multiple myeloma, and 36 with leukemia or myelodysplastic syndromes) will be accrued for this study within 1 year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE Drug: vorinostat
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 2008
Actual Primary Completion Date December 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Histologically confirmed advanced primary or metastatic solid tumor, including, but not limited to, the following:

      • Androgen-independent prostate cancer
      • Breast cancer
      • Ovarian cancer
      • Head and neck cancer
      • Non-small cell lung cancer
      • Bladder cancer
      • Kidney cancer
    • Diagnosis of lymphoma, multiple myeloma, leukemia, or myelodysplastic syndromes (MDS), including, but not limited to, the following:

      • Intermediate-grade or follicular non-Hodgkin's lymphoma
      • Hodgkin's lymphoma
  • Patients with lymphoma or multiple myeloma must be ineligible for peripheral blood stem cell transplantation
  • For patients with solid tumors (except prostate cancer):

    • Disease progression based on development of new lesions or an increase in pre-existing lesions
    • Biochemical marker increase must not be sole criterion for disease progression
  • For prostate cancer patients only:

    • Disease progression based on rising prostate-specific antigen (PSA) values, transaxial imaging, or radionuclide scans
    • Increase in disease-related symptoms must not be sole manifestation of progression
    • Patients receiving an antiandrogen as part of first-line hormonal therapy must show disease progression off of the antiandrogen prior to study
    • Biochemical progression (at least 25% increase over range of values) defined as 1 of the following:

      • Rising PSA documented by at least 3 consecutive measurements obtained at least 1 week apart
      • Rising PSA documented by at least 2 consecutive measurements obtained more than 1 month apart
    • PSA at least 4 ng/mL

      • Testosterone no greater than 50 ng/mL
      • If no prior orchiectomy, must maintain castrate levels of testosterone
  • Disease must be refractory to standard therapy or for which no curative therapy exists
  • No active CNS or epidural tumors
  • Hormone receptor status:

    • Not specified NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Male or female

Menopausal status

  • Not specified

Performance status

  • Karnofsky 70-100%

Life expectancy

  • Not specified

Hematopoietic

  • WBC at least 3,500/mm^3
  • Platelet count at least 100,000/mm^3 (patients with solid tumors)
  • Platelet count greater than 25,000/mm^3 (patients with hematologic malignancy)
  • Absolute neutrophil count at least 500/mm^3 (patients with hematologic malignancy)

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST and ALT no greater than 3 times ULN
  • PT no greater than 15 seconds

Renal

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular

  • No New York Heart Association class III or IV heart disease

Pulmonary

  • No severe debilitating pulmonary disease

Other

  • No infection requiring IV antibiotics
  • No other severe medical problems that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics

Chemotherapy

  • At least 4 weeks since prior chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 4 weeks since prior ketoconazole
  • At least 2 weeks since prior steroids for patients with lymphoma
  • Concurrent gonadotropin-releasing hormone analogs or diethylstilbestrol to maintain castrate levels of testosterone allowed for prostate cancer patients
  • No concurrent ketoconazole

Radiotherapy

  • At least 4 weeks since prior radiotherapy
  • No concurrent radiotherapy to sole measurable lesion

Surgery

  • See Disease Characteristics
  • No concurrent surgery

Other

  • Recovered from all prior therapy
  • At least 4 weeks since prior palliative therapy for solid tumor patients with progressive metastatic disease (if present)
  • At least 4 weeks since prior investigational anticancer therapeutic drugs
  • At least 2 weeks since prior conventional cytotoxic therapy for patients with leukemia or MDS
  • At least 4 weeks since prior investigational therapy for patients with leukemia or MDS
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00045006
Other Study ID Numbers  ICMJE MSKCC-01021
CDR0000256306 ( Registry Identifier: PDQ (Physician Data Query) )
ATON-0101
NCI-G02-2099
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: William K. Kelly, DO Memorial Sloan Kettering Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date October 2003

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP