Brief Title
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version 1.1)
Condition
Brenner Tumor
Intervention
belinostat
Study Arms / Comparison Groups
Treatment
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
29
Start Date
December 2009
Completion Date
July 29, 2012
Primary Completion Date
July 2012
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Don Dizon, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00993616
Organization ID
NCI-2010-01663
Secondary IDs
NCI-2010-01663
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Collaborators
Gynecologic Oncology Group
Study Sponsor
Don Dizon, Principal Investigator, Gynecologic Oncology Group
Verification Date
July 2019