Clinical trial NCT00993616: 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
Official title: A Phase II Evaluation of Belinostat (NSC #726630) and Carboplatin (NSC #241240) in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brenner Tumor
Fallopian Tube Cancer
Ovarian Clear Cell Cystadenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mixed Epithelial Carcinoma
Ovarian Mucinous Cystadenocarcinoma
Ovarian Serous Cystadenocarcinoma
Ovarian Undifferentiated Adenocarcinoma
Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2009-10-12
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version 1.1)
timeFrame: From study entry, up to 5 years
measure: Frequency and Severity of Observed Adverse Effects Graded According to NCI CTCAE Version 3.0
timeFrame: Every cycle during treatment and 30 days after the end of treatment
measure: Progression Free Survival at 6 Months
timeFrame: Every other cycle for 6 months
Secondary outcomes:
Other outcomes:
measure: Duration of Progression-free Interval for All Patients
timeFrame: up to 5 years
Locations:
city: Hartford
country: United States
facility: Saint Francis Hospital and Medical Center
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates-West Des Moines
state: Iowa
city: Clive
country: United States
facility: Mercy Cancer Center-West Lakes
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association CCOP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Laurel
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: West Des Moines
country: United States
facility: Mercy Medical Center-West Lakes
state: Iowa
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Saint Luke's South Hospital
state: Kansas
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Franklin Square Hospital Center
state: Maryland
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Health Care
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium Community Clinical Oncology Program
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology - Escanaba
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Regional Medical Center-West Flint Campus
state: Michigan
city: Iron Mountain
country: United States
facility: Green Bay Oncology - Iron Mountain
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Saint Joseph Mercy Port Huron
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Saint Joseph Health Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Heartland Hematology and Oncology Associates Incorporated
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Lee's Summit
country: United States
facility: Saint Luke's East - Lee's Summit
state: Missouri
city: Liberty
country: United States
facility: Liberty Hospital
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Joseph
country: United States
facility: Saint Joseph Oncology Inc
state: Missouri
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Cancer Institute
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Houston
country: United States
facility: Lyndon Baines Johnson General Hospital
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic Gynecological Oncology
state: Virginia
city: Green Bay
country: United States
facility: Green Bay Oncology at Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology Limited at Saint Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Mary's Hospital
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Hospital
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Door County Cancer Center
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Gynecologic Oncology Group
name: Don Dizon
role: PRINCIPAL_INVESTIGATOR
References: