Phase III Randomized Study of Vorinostat (SAHA) in Patients With Progressive or Relapsed Advanced Malignant Pleural Mesothelioma

Vorinostat is a Phase III Clinical Trial for malignant mesothelioma that is offered at several clinics Nationwide, including the UCLA Medical School in Los Angeles, California (Investigator Dr. Robert Cameron).

RATIONALE: Drugs used in chemotherapy, such as vorinostat, 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. It is not yet known whether vorinostat is more effective than a placebo in treating malignant mesothelioma.

PURPOSE: This randomized phase III trial is studying vorinostat to see how well it works compared to placebo in treating patients with progressive or relapsed advanced malignant mesothelioma.

Study Type: Interventional Study Design: Treatment

Official Title: Phase III Randomized Study of Vorinostat (SAHA) in Patients With Progressive or Relapsed Advanced Malignant Pleural Mesothelioma

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

OBJECTIVES:

Primary

Compare the overall survival of patients with progressive or relapsed advanced malignant pleural mesothelioma treated with vorinostat (SAHA) vs placebo. Determine the overall safety and toxicity of vorinostat (SAHA) in these patients.

Secondary

  • Compare the overall objective response rate and progression-free survival of patients treated with vorinostat (SAHA) vs placebo.
  • Compare the dyspnea score on the lung cancer symptom scale (modified for mesothelioma) in patients treated with these drugs.
  • Compare the percent change from baseline in forced vital capacity in patients treated with these drugs.
  • Compare the quality of life of patients treated with these drugs

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to histologic subtype (epithelial vs nonepithelial), Karnofsky performance status (70-80% vs 80-100%), and number of prior chemotherapy failures (first vs second line failures). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral vorinostat (SAHA) twice daily on days 1-3, 8-10, and 15-17.
  • Arm II: Patients receive oral placebo twice daily on days 1-3, 8-10, and 15-17. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 3 weeks for up to 6 months during study treatment, within 1 month after completion of study treatment, and then every 2 months thereafter.

After completion of study treatment, patients are followed within 1 month and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 660 patients will be accrued for this study.

Eligibility

Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed advanced malignant pleural mesothelioma, including 1 of the following subtypes:
  • Epithelial
  • Sarcomatoid
  • Mixed histology
  • Disease progressed or relapsed after 1-2 prior standard systemic therapies that included pemetrexed disodium and either cisplatin or carboplatin
  • Pemetrexed disodium must have been part of the most recent regimen
  • Pleural thickness ≥ 1.5 cm in diameter on spiral CT scan
  • No uncontrolled brain metastases (e.g., previously treated brain metastases that are not stable within the past 6 weeks)

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • PT ≤ 1.5 times upper limit of normal (ULN) except if receiving therapeutic anticoagulation
  • ALT and AST ≤ 2.5 times ULN (5 times ULN if enzyme abnormalities are due to liver metastases)
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 effective barrier methods of contraception during and for at least 1 month after study treatment
  • No active infection requiring IV antibiotics, antivirals, or antifungals within the past 2 weeks
  • No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No known HIV infection or HIV-related malignancy
  • No known allergy to any component of the study drug
  • No other poorly controlled illness or situation that would preclude study compliance, including, but not limited to, the following:
  • Acute or chronic graft vs host disease
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric or social conditions

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 4 weeks since prior radiotherapy
  • No prior treatment with a histone deacetylase (HDAC) inhibitor* (e.g., depsipeptide, MS-275, LAQ-824, PXD-101, or valproic acid) NOTE: * Patients who have received these agents for other indications, such as epilepsy, may enroll on vorinostat (SAHA) trials after a 30-day washout period
  • No prior gastrointestinal surgery or other procedures that, in the opinion of the investigator, would interfere with the absorption or swallowing of the study drug
  • No concurrent radiotherapy to non-target lesions
  • No other concurrent anticancer therapy

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00290784

California

Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, 90095-1781
United States; Recruiting Clinical Trials Office - Jonsson Comprehensive Cancer Center 310-794-8075

Maryland

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, 20892-1182
United States; Recruiting NCI Clinical Studies Support 888-NCI-1937

Study chairs or principal investigators

Raffit Hassan, MD, Study Chair, National Cancer Institute (NCI)

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For further information refer to the sites below.

http://clinicaltrial.gov/ct/show/NCT00290784?order=3

http://www.cancer.gov/clinicaltrials/NCI-06-C-0040

http://www.merckcancertrials.com/secure/mesothelioma/about.html

*** POSTED MARCH 27, 2006 ***