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Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00301756
First received: March 9, 2006
Last updated: April 11, 2013
Last verified: April 2013
History of Changes
  Purpose

This phase II trial is studying how well belinostat works in treating patients with advanced ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer or ovarian low malignant potential tumors. Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Fallopian Tube Cancer
Primary Peritoneal Cavity Cancer
Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor
Recurrent Ovarian Epithelial Cancer
Stage III Borderline Ovarian Surface Epithelial-stromal Tumor
Stage III Ovarian Epithelial Cancer
Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor
Stage IV Ovarian Epithelial Cancer
 Drug: belinostat
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of PXD101 in Platinum Resistant Epithelial Ovarian Tumors and Micropapillary/Borderline (LMP) Ovarian Tumors

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Efficacy of belinostat in terms of complete or partial response; disappearance of all target lesions or at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) or Rustin criteria.


Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Assessed by RECIST criteria. Summarized using summary statistics, such as the mean, median, counts and proportion.

  • Duration of CA-125 response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Assessed according to the Gynecologic Cancer Intergroup (GCIG) criteria.

  • Stable disease rate, defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized using summary statistics, such as the mean, median, counts and proportion. Assessed by RECIST criteria.

  • Duration of response [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years ] [ Designated as safety issue: No ]
    Summarized using summary statistics, such as the mean, median, counts and proportion. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Progression-free survival [ Time Frame: Duration of time from start of treatment to time of progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    Computed using the Kaplan-Meier method. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Overall Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Computed using the Kaplan-Meier method. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Safety and tolerability of belinostat in patients with platinum resistant and micropapillary/ borderline ovarian tumors [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Tabulated using counts and proportions detailing frequently occurring, serious and related events of interest.

  • Relationship between clinical and pharmacodynamic effects of belinostat in patients with platinum resistant and micropapillary/ borderline ovarian tumors [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized using summary statistics, such as the mean, median, and range. Tested using one-sample t-tests or Wilcoxon rank sum tests. Logistic regression analysis will be used to test significance.


Estimated Enrollment: 65
Study Start Date: September 2006
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive belinostat IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
 Drug: belinostat
Given IV
Other Name: PXD101

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the antitumor activity of PXD 101 as a single agent in the following patient population using objective response rates (complete and partial): a) Platinum resistant ovarian carcinoma (progression within 6 months of platinum based therapy); b) Micropapillary / borderline (Low Malignant potential) ovarian carcinoma.

SECONDARY OBJECTIVES:

I. To determine the antitumor activity of PXD 101 with regards to stable disease rates, duration of response, progression- free, median and overall survival rates as well as determine the safety and tolerability this drug.

TERTIARY OBJECTIVES:

I. To determine the relationship between clinical and pharmacodynamic effects of PXD101 in patients with platinum resistant and micropapillary tumors undergoing treatment with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (micropapillary or borderline ovarian tumor vs platinum-resistant ovarian epithelial, primary peritoneal, or fallopian tube cancer).

Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of 1 of the following:

    • Micropapillary or borderline (low malignant potential) ovarian tumors

      • No more than 3 prior chemotherapy regimens

    • Histologically or cytologically confirmed ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer

      • Recurrent or persistent disease despite initial platinum-based chemotherapy (i.e., platinum-resistant disease)

        • Disease progression within 6 months after completion of chemotherapy

        • Received 1-3 prior chemotherapy regimens

          • At least 1 regimen must have included a platinum agent (carboplatin or cisplatin)

  • Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan

    • Measurable disease outside the field of prior radiotherapy OR disease progression after completion of radiotherapy
  • No known brain metastases
  • ECOG performance status (PS) ≤ 2 OR Karnofsky PS ≥ 60%
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to sulfonamides, arginine, and compounds of similar chemical or biological composition to PXD101

  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Psychiatric illness or social situation that would limit compliance with study requirements
  • No bowel obstruction unless receiving parenteral support
  • No marked prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 500 msec)
  • No long-QT syndrome

  • No significant cardiovascular disease, including any of the following:

    • Unstable angina pectoris
    • Uncontrolled hypertension
    • Congestive heart failure related to primary cardiac disease
    • Any condition requiring anti-arrhythmic therapy
    • Ischemic or severe valvular heart disease
    • Myocardial infarction within the past 6 months
  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) and recovered
  • At least 4 weeks since prior radiotherapy or surgery and recovered
  • No prior radiotherapy to > 40% of bone marrow
  • At least 2 weeks since prior valproic acid

  • No concurrent medication that may cause torsades de pointes, including any of the following:

    • Disopyramide
    • Dofetilide
    • Ibutilide
    • Procainamide
    • Quinidine
    • Sotalol
    • Bepridil
    • Amiodarone
    • Arsenic trioxide
    • Cisapride
    • Methadone
    • Lidoflazine
    • Clarithromycin
    • Erythromycin
    • Halofantrine
    • Pentamidine
    • Sparfloxacin
    • Domperidone
    • Droperidol
    • Chlorpromazine
    • Haloperidol
    • Mesoridazine
    • Thioridazine
    • Pimozide
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00301756

Locations
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, Canada, M5G 2M9
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Amit Oza Princess Margaret Hospital Phase 2 Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00301756     History of Changes
Other Study ID Numbers: NCI-2009-00144, PHL-041, PMH-PHL-041, CDR0000459798, NCI-7267, N01CM62203
Study First Received: March 9, 2006
Last Updated: April 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
 Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on May 16, 2013