Vorinostat in Treating Patients With Recurrent or Persistent Ovarian Epithelial or Primary Peritoneal Cavity Cancer

Condition(s) targeted: Ovarian Cancer; Peritoneal Cavity Cancer

Intervention: vorinostat (Drug); chemotherapy (Procedure); enzyme inhibitor therapy (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Gynecologic Oncology Group

Official(s) and/or principal investigator(s):
Susan C. Modesitt, MD, Study Chair, Affiliation: Lucille P. Markey Cancer Center at University of Kentucky

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.

PURPOSE: This phase II trial is studying how well vorinostat works in treating patients with recurrent or persistent ovarian epithelial or primary peritoneal cavity cancer.

Official title: A Phase II Evaluation of Vorinostat, (SAHA, NCI-Supplied Agent [NSC #701852, IND #71976]) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma

Study design: Treatment, Non-Randomized

Primary outcome:

Progression-free at 6 months

Toxicity as measured by CTCAE v 3.0 at every course

Secondary outcome:

Clinical response rate as measured by RECIST criteria after every 2 courses

Duration of progression-free and overall survival

Detailed description: OBJECTIVES:

Primary

- Determine the 6-month progression-free survival rate in patients with recurrent or

persistent ovarian epithelial or primary peritoneal cavity cancer treated with vorinostat.

- Determine the toxicity of this drug, in terms of the frequency and severity of adverse

reactions in these patients.

Secondary

- Determine the clinical response rate (partial response and complete response) in

patients treated with this drug.

- Determine the duration of progression-free survival and overall survival of patients

treated with this drug.

- Determine the impact of prognostic variables (e. g., platinum sensitivity, performance

status, and cellular histology) in patients treated with this drug.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive oral vorinostat twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within approximately 1 year.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed ovarian epithelial or primary peritoneal cavity cancer

- Recurrent or persistent disease

- Disease progression during OR persistent disease after completion of 1 prior

platinum-based chemotherapy regimen (containing carboplatin, cisplatin, or other organoplatinum compound) for primary disease

- Initial treatment may have included high-dose, consolidation, noncytotoxic

agents, or extended therapy administered after surgical or non-surgical assessment

- Treatment-free interval after completion of platinum-based chemotherapy must

have been < 12 months

- Measurable disease, defined as ≥ 1 unidimensionally measurable target* lesion ≥ 20 mm

by conventional techniques (e. g., palpation, plain x-ray, CT scan, or MRI) OR ≥ 10 mm by spiral CT scan NOTE: *Tumors within a previously irradiated field are not considered target lesions unless there has been subsequent disease progression at least 90 days after prior radiotherapy

- Not eligible for a higher priority GOG protocol (i. e., any active phase III GOG

protocol for the same patient population)

- No known brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- GOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin ≤ 1. 5 times upper limit of normal (ULN)

- SGOT ≤ 2. 5 times ULN

- Alkaline phosphatase ≤ 2. 5 times ULN

Renal

- Creatinine ≤ 1. 5 times ULN

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Gastrointestinal

- Able to take oral medication

- No bowel obstruction

- No persistent vomiting

- No parenteral feeding

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 1 month after

completion of study treatment

- No neuropathy (sensory and motor) > grade 1

- No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

- No active infection requiring antibiotics

- No psychiatric illness or social situation that would preclude study compliance

- No history of allergic reaction attributed to compounds of similar chemical or

biological composition to vorinostat

- No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 4 weeks since prior immunotherapy for the malignancy

Chemotherapy

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for

the malignancy and recovered

- No more than 2 prior cytotoxic chemotherapy regimens for recurrent or persistent

disease

- No prior non-cytotoxic chemotherapy for recurrent or persistent disease, unless

therapy was part of the primary treatment regimen

- No prior vorinostat

Endocrine therapy

- At least 1 week since prior hormonal therapy for the malignancy

- Concurrent hormone replacement therapy allowed

Radiotherapy

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy for the malignancy and recovered

- No prior radiotherapy to > 25% of bone marrow

Surgery

- At least 4 weeks since prior surgery for the malignancy and recovered

Other

- At least 4 weeks since other prior therapy for the malignancy

- At least 30 days since prior and no concurrent valproic acid

- Concurrent oral anticoagulants (i. e., warfarin) allowed provided there is increased

vigilance with respect to monitoring PT/INR for the first 2 courses of study therapy or if there are any signs of bleeding

- No prior anticancer therapy that would preclude study participation

- No concurrent combination anti-retroviral therapy for HIV-positive patients

- No other concurrent investigational agents

Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, Alabama 35294, United States

Providence Saint Joseph Medical Center - Burbank, Burbank, California 91505, United States

New Britain General Hospital, New Britain, Connecticut 06050, United States

Beebe Medical Center, Lewes, Delaware 19958, United States

CCOP - Christiana Care Health Services, Newark, Delaware 19713, United States

St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States

Holden Comprehensive Cancer Center at University of Iowa, Iowa City, Iowa 52242, United States

Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0293, United States

Union Hospital Cancer Center at Union Hospital, Elkton MD, Maryland 21921, United States

Siteman Cancer Center at Barnes-Jewish Hospital, St Louis, Missouri 63110, United States

Methodist Cancer Center at Methodist Hospital - Omaha, Omaha, Nebraska 68114, United States

Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees, Voorhees, New Jersey 08043, United States

Sister Patricia Lynch Regional Cancer Center at Holy Name Hospital, Teaneck, New Jersey 07666, United States

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

David L. Rike Cancer Center at Miami Valley Hospital, Dayton, Ohio 45409, United States

Riverside Methodist Hospital Cancer Care, Columbus, Ohio 43214-3998, United States

Rapid City Regional Hospital, Rapid City, South Dakota 57701, United States

Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, United States

University Cancer Center at University of Washington Medical Center, Seattle, Washington 98195-6043, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: July 2005
Last updated: February 29, 2008