Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vorinostat in Treating Patients With Progressive or Relapsed Advanced Malignant Mesothelioma

Basic Trial Information

Objectives

Primary

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

Secondary

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

Entry 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)

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

Patient Characteristics:

• Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

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

Outcomes

Overall survival
Toxicity (grade 3 or 4) as measured by NCI CTCAE v3.0

Overall objective response rate as measured by RECIST criteria
Time to progression
Dyspnea as measured by the Lung Cancer Symptom Scale-Mesothelioma at week 12
Forced vital capacity at week 12

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Raffit Hassan, MD, Protocol chair		Ph: 301-451-8742

Registry Information
Official Title		A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Oral Suberoylanilide Hydroxamic Acid (L-001079038) in Patients With Advanced Malignant Pleural Mesothelioma Previously Treated With Systemic Chemotherapy
Trial Start Date		2006-05-31
Registered in ClinicalTrials.gov		NCT00265577
Date Submitted to PDQ		2005-12-08
Information Last Verified		2006-10-24

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