Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin

Phase 2

Completed

Conditions: Fallopian Tube Cancer
Ovarian Clear Cell Cystadenocarcinoma
Ovarian Serous Cystadenocarcinoma
Ovarian Undifferentiated Adenocarcinoma
Brenner Tumor
Ovarian Endometrioid Adenocarcinoma
Ovarian Mucinous Cystadenocarcinoma
Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Ovarian Mixed Epithelial Carcinoma

Interventions: Drug: belinostat
Drug: carboplatin

Registration Number: NCT00993616

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying how well giving belinostat together with carboplatin works in treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer that did not respond to carboplatin or cisplatin. Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving belinostat together with carboplatin may kill more tumor cells.

Detailed Description: PRIMARY OBJECTIVES:

I. To estimate the antitumor activity of belinostat and carboplatin in patients with persistent or recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer, measured by objective response rate and the frequency of progression- free survival at 6 months.

II. To determine the nature and degree of toxicity of belinostat in combination with carboplatin in this cohort of patients.

OUTLINE: This is a multicenter study.

Patients receive belinostat IV over 30 minutes on days 1-5 and carboplatin IV over 30-60 minutes on day 3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who are clinically responding or who, in the opinion of their physician, would continue to benefit from treatment may continue treatment beyond 6 courses.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 29

Inclusion Criteria

Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report
Patients with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.)
All patients must have measurable disease as defined by RECIST 1.1; measureable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be >= 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Patients must not be eligible for a higher priority GOG protocol, if one exists; in general, this would refer to any active GOG Phase III or Rare Tumor protocol for the same patient population
Patients must have a GOG Performance Status of 0, 1, or 2
Recovery from effects of recent surgery, radiotherapy, or chemotherapy
- Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI)
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
- Any other prior therapy directed at the malignant tumor, including biological and immunologic agents, must be discontinued at least three weeks prior to registration
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included non-cytotoxic therapy, intraperitoneal therapy, high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment
Patients must be considered platinum resistant or refractory according to the following criteria:
- Patients must have had progression of disease on or within 6 months of their last platinum dose
- Progression of disease is defined according to RECIST 1.1
- The development of CA125 elevation on or within 6 months of last platinum treatment, in the absence of radiographic progression according to RECIST 1.1, is not considered platinum resistance for the purposes of this study
Patients who have NOT received prior therapy with taxane-based chemotherapy MUST receive a second regimen that includes paclitaxel or docetaxel
Patients must be considered paclitaxel-resistant, i.e., have had a treatment-free interval following paclitaxel of less than six months, or have progressed during paclitaxel-based therapy
Patients must have NOT received any additional cytotoxic chemotherapy for management of recurrent or persistent disease, including retreatment with initial chemotherapy regimens except as noted above; (note: Optimal evaluation of the safety and efficacy of new chemotherapy regimens is best performed in patients with minimal prior therapy; non-investigational therapy, such as retreatment with platinum and/or paclitaxel, is non-curative in the setting of recurrent disease, and can generally be safely administered to patients following participation in a phase II trial)
Patients are allowed to receive, but are not required to receive, one additional non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition:
- Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction
Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to the NCI Common Terminology Criteria (CTCAE v3.0) grade 1
Platelets greater than or equal to 100,000/mcl
Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), per CTCAE v.3.0 grade 1
Bilirubin less than or equal to 1.5 x ULN (CTCAE v.3.0 grade 1)
SGOT (AST) less than or equal to 3 x ULN (per the CTCAE v.3.0 grade 1)
Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v.3.0 grade 1)
Neuropathy (sensory and motor) less than or equal to the CTCAE v3.0 grade 1
Patients must have signed an approved informed consent and authorization permitting release of personal health information
Patients must meet pre-entry requirements
Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception

Exclusion Criteria

Patients who have had prior therapy with Belinostat (PXD101) or other HDAC inhibitors
Patients who have received radiation to more than 25% of marrow-bearing areas
Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, and other specific malignancies as noted below, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian cancer are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian cancer are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
Patients must not use concomitant medications on PXD infusion days that may cause Torsade de Pointes; medications associated with this risk include:
- Amiodarone, Arsenic trioxide, Bepridil, Cisapride, Disopyramide, Dofetilide, Droperidol, Erythromycin, Felbamate, Flecainide, Fluoxetine, Halofantrine, Haloperidol, Ibutilide, Levofloxacin, Mesoridazine, Pentamidine, Procainamide, Quinidine, Sotalol, Sparfloxacin, or Thioridazine
Patients with significant cardiovascular disease defined as:
- Unstable angina pectoris, uncontrolled hypertension (blood pressure > 150/90 despite maximal medical therapy), congestive heart failure related to primary cardiac disease, any condition requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or history of myocardial infarction within 6 months of trial entry
Patients who are pregnant or nursing

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	carboplatin	Patients receive belinostat IV over 30 minutes on days 1-5 and carboplatin IV over 30-60 minutes on day 3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who are clinically responding or who, in the opinion of their physician, would continue to benefit from treatment may continue treatment beyond 6 courses.
Treatment	belinostat	Patients receive belinostat IV over 30 minutes on days 1-5 and carboplatin IV over 30-60 minutes on day 3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who are clinically responding or who, in the opinion of their physician, would continue to benefit from treatment may continue treatment beyond 6 courses.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival at 6 Months	Every other cycle for 6 months	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version 1.1)	From study entry, up to 5 years	Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (version 1.1): Complete Response (CR) is disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Increasing Disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest
Frequency and Severity of Observed Adverse Effects Graded According to NCI CTCAE Version 3.0	Every cycle during treatment and 30 days after the end of treatment

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (81): Green Bay Oncology - Oconto Falls
🇺🇸
Oconto Falls, Wisconsin, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Women's Cancer Center of Nevada
🇺🇸
Las Vegas, Nevada, United States
Heartland Regional Medical Center
🇺🇸
Saint Joseph, Missouri, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Tulsa Cancer Institute
🇺🇸
Tulsa, Oklahoma, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Truman Medical Center
🇺🇸
Kansas City, Missouri, United States
Saint Francis Hospital and Medical Center
🇺🇸
Hartford, Connecticut, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Indiana University Medical Center
🇺🇸
Indianapolis, Indiana, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸
Clive, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
🇺🇸
Des Moines, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸
Clive, Iowa, United States
Mercy Medical Center-West Lakes
🇺🇸
West Des Moines, Iowa, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Greater Baltimore Medical Center
🇺🇸
Baltimore, Maryland, United States
Franklin Square Hospital Center
🇺🇸
Baltimore, Maryland, United States
Union Hospital of Cecil County
🇺🇸
Elkton, Maryland, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Lahey Hospital and Medical Center
🇺🇸
Burlington, Massachusetts, United States
Oakwood Hospital
🇺🇸
Dearborn, Michigan, United States
Green Bay Oncology - Escanaba
🇺🇸
Escanaba, Michigan, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸
Port Huron, Michigan, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Saint Luke's East - Lee's Summit
🇺🇸
Lee's Summit, Missouri, United States
Liberty Hospital
🇺🇸
Liberty, Missouri, United States
Saint Joseph Oncology Inc
🇺🇸
Saint Joseph, Missouri, United States
Stony Brook University Medical Center
🇺🇸
Stony Brook, New York, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Akron General Medical Center
🇺🇸
Akron, Ohio, United States
Carolinas Medical Center
🇺🇸
Charlotte, North Carolina, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
University of Pennsylvania/Abramson Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Women and Infants Hospital
🇺🇸
Providence, Rhode Island, United States
Lyndon Baines Johnson General Hospital
🇺🇸
Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Green Bay Oncology Limited at Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Carilion Clinic Gynecological Oncology
🇺🇸
Roanoke, Virginia, United States
Green Bay Oncology at Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Holy Family Memorial Hospital
🇺🇸
Manitowoc, Wisconsin, United States
Bay Area Medical Center
🇺🇸
Marinette, Wisconsin, United States
Door County Cancer Center
🇺🇸
Sturgeon Bay, Wisconsin, United States
Green Bay Oncology - Sturgeon Bay
🇺🇸
Sturgeon Bay, Wisconsin, United States
Saint Luke's South Hospital
🇺🇸
Overland Park, Kansas, United States
Shawnee Mission Medical Center
🇺🇸
Shawnee Mission, Kansas, United States
Menorah Medical Center
🇺🇸
Overland Park, Kansas, United States
University of Massachusetts Memorial Health Care
🇺🇸
Worcester, Massachusetts, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
Green Bay Oncology - Iron Mountain
🇺🇸
Iron Mountain, Michigan, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸
Ann Arbor, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Iowa Oncology Research Association CCOP
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸
Des Moines, Iowa, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
Heartland Hematology and Oncology Associates Incorporated
🇺🇸
Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸
Kansas City, Missouri, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States