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

Fallopian Tube Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00993616
• Other study ID #: NCI-2010-01663
• Secondary ID: NCI-2010-01663CD
• Status: Completed
• Phase: Phase 2
• Start date: December 2009
• Est. completion date: July 29, 2012

Study information

• Verified date: July 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 29, 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Brenner Tumor
• Carcinoma
• Carcinoma, Endometrioid
• Carcinoma, Ovarian Epithelial
• Cystadenocarcinoma
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• 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

Intervention

Drug:
• belinostat
Given IV
• carboplatin
Given IV

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Gynecologic Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of Progression-free Interval for All Patients		up to 5 years
Primary	Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version 1.1)	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	From study entry, up to 5 years
Primary	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
Primary	Progression Free Survival at 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.	Every other cycle for 6 months