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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

Primary Purpose

Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma, Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Belinostat
Laboratory Biomarker Analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fallopian Tube Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Histologically/cytologically confirmed ovarian epithelial cancer, primary peritoneal carcinoma or fallopian tube cancer that recurred despite initial platinumbased therapy OR micropapillary/borderline (Low Malignant Potential) tumors of ovary Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan Patients in the platinum resistant (progression within 6 months of platinum based therapy) group: must have had no more than a total of 3 prior chemotherapy regimens; at least one prior regimen will have contained a platinum agent (carboplatin or cisplatin) Patients with micropapillary or borderline (LMP) tumors: must have had no more than a total of 3 prior chemotherapy regimens Patients must have completed any prior chemotherapy, radiotherapy or surgery at least 4 weeks (at least 6 weeks for nitrosureas and mitomycin C) before study entry and patients must have recovered from the toxic effects from any prior therapy; patients must not have had more than 40% of their bone marrow radiated and must have either measurable disease outside the field or progression post radiation therapy Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Leukocytes >= 3.0 x 10^9/L Absolute neutrophil count >= 1.5 x 10^9/L Platelets >= 100 x 10^9/L Total bilirubin =< institutional upper limit of normal Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Biopsies are not mandatory but patients will be asked to undergo tumor biopsy once before and once during experimental therapy if considered medically safe for them to do so; patients must be willing to have the peripheral blood mononuclear cell (PBMC) procured prior to and during the treatment Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of PXD101 will be determined following review of their case by the Principal Investigator; efforts should be made to switch patients who are taking enzyme-inducing anticonvulsant agents to other medications Women of child-bearing potential and their partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier A marked baseline prolongation of QT/corrected QT (QTc) interval, e.g., repeated demonstration of a QTc interval > 500msec; long QT syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes (disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, bepridil, amiodarone, arsenic trioxide, cisapride, lidoflazine, clarithromycin, erythromycin, halofantrine, pentamidine, sparfloxacin, domperidone, droperidol, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide & methadone) Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, a condition requiring anti-arrythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry Patients may not be receiving any other investigational agents Patients with known brain metastases should be excluded from this clinical trial History of allergic reactions attributed to sulfonamides, arginine and compounds of similar chemical or biologic composition to PXD101 Patients should not have taken valproic acid, another histone deacytelase inhibitor, for at least 2 weeks prior to enrollment Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients with bowel obstruction would not be eligible because of compromised functional status unless they are on parenteral support Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PXD101 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Sites / Locations

  • Juravinski Cancer Centre at Hamilton Health Sciences
  • Odette Cancer Centre- Sunnybrook Health Sciences Centre
  • University Health Network Princess Margaret Cancer Center P2C
  • University Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (enzyme inhibitor therapy)

Arm Description

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.

Outcomes

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 of Target Lesions, Taking as Reference the Baseline Sum LD
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. Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) or Rustin criteria.

Secondary Outcome Measures

Time to Disease Progression (Epithelial Ovarian Cancer Group)
Assessed by RECIST criteria. Summarized using summary statistics, such as the mean, median, counts and proportion.
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 (Low Malignant Potential Group)
Stable disease rate, defined as neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive disease, taking as reference the smallest sum LD since the treatment started. Summarized using summary statistics, such as the mean, median, counts and proportion. Assessed by RECIST criteria.
Duration of Response
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
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
Computed using the Kaplan-Meier method. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Number of Grade 3 Adverse Events Using the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Events of Thrombosis, Hypersensitivity and ALP will be tabulated.
Time to Disease Progression (Low Malignant Potential or Micropapillary / Borderline Ovarian Tumour Group)
Assessed by RECIST criteria. Summarized using summary statistics, such as the mean, median, counts and proportion.
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 (Epithelial Ovarian Cancer Group)
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. Summarized using summary statistics, such as the mean, median, counts and proportion. Assessed by RECIST criteria.

Full Information

First Posted
March 9, 2006
Last Updated
July 20, 2018
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00301756
Brief Title
Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors
Official Title
A Phase 2 Study of PXD101 in Platinum Resistant Epithelial Ovarian Tumors and Micropapillary/Borderline (LMP) Ovarian Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial studies how well belinostat works in treating patients with ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer that have spread to other places in the body or ovarian low malignant potential tumors. Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma, Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor, Recurrent Ovarian Carcinoma, Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor, Stage III Ovarian Cancer, Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor, Stage IV Ovarian Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (enzyme inhibitor therapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Belinostat
Other Intervention Name(s)
Beleodaq, PXD 101, PXD101
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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 of Target Lesions, Taking as Reference the Baseline Sum LD
Description
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. Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) or Rustin criteria.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Time to Disease Progression (Epithelial Ovarian Cancer Group)
Description
Assessed by RECIST criteria. Summarized using summary statistics, such as the mean, median, counts and proportion.
Time Frame
Up to 5 years
Title
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 (Low Malignant Potential Group)
Description
Stable disease rate, defined as neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive disease, taking as reference the smallest sum LD since the treatment started. Summarized using summary statistics, such as the mean, median, counts and proportion. Assessed by RECIST criteria.
Time Frame
Up to 5 years
Title
Duration of Response
Description
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.
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
Title
Progression-free Survival
Description
Computed using the Kaplan-Meier method. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Time Frame
Duration of time from start of treatment to time of progression, assessed up to 5 years
Title
Overall Survival
Description
Computed using the Kaplan-Meier method. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Time Frame
Up to 5 years
Title
Number of Grade 3 Adverse Events Using the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Description
Events of Thrombosis, Hypersensitivity and ALP will be tabulated.
Time Frame
Up to 5 years
Title
Time to Disease Progression (Low Malignant Potential or Micropapillary / Borderline Ovarian Tumour Group)
Description
Assessed by RECIST criteria. Summarized using summary statistics, such as the mean, median, counts and proportion.
Time Frame
Up to 5 years
Title
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 (Epithelial Ovarian Cancer Group)
Description
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. Summarized using summary statistics, such as the mean, median, counts and proportion. Assessed by RECIST criteria.
Time Frame
Up to 5 years
Other Pre-specified Outcome Measures:
Title
Relationship Between Clinical and Pharmacodynamic Effects of Belinostat in Patients With Platinum Resistant and Micropapillary/ Borderline Ovarian Tumors
Description
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.
Time Frame
Up to 5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically/cytologically confirmed ovarian epithelial cancer, primary peritoneal carcinoma or fallopian tube cancer that recurred despite initial platinumbased therapy OR micropapillary/borderline (Low Malignant Potential) tumors of ovary Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan Patients in the platinum resistant (progression within 6 months of platinum based therapy) group: must have had no more than a total of 3 prior chemotherapy regimens; at least one prior regimen will have contained a platinum agent (carboplatin or cisplatin) Patients with micropapillary or borderline (LMP) tumors: must have had no more than a total of 3 prior chemotherapy regimens Patients must have completed any prior chemotherapy, radiotherapy or surgery at least 4 weeks (at least 6 weeks for nitrosureas and mitomycin C) before study entry and patients must have recovered from the toxic effects from any prior therapy; patients must not have had more than 40% of their bone marrow radiated and must have either measurable disease outside the field or progression post radiation therapy Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Leukocytes >= 3.0 x 10^9/L Absolute neutrophil count >= 1.5 x 10^9/L Platelets >= 100 x 10^9/L Total bilirubin =< institutional upper limit of normal Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Biopsies are not mandatory but patients will be asked to undergo tumor biopsy once before and once during experimental therapy if considered medically safe for them to do so; patients must be willing to have the peripheral blood mononuclear cell (PBMC) procured prior to and during the treatment Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of PXD101 will be determined following review of their case by the Principal Investigator; efforts should be made to switch patients who are taking enzyme-inducing anticonvulsant agents to other medications Women of child-bearing potential and their partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier A marked baseline prolongation of QT/corrected QT (QTc) interval, e.g., repeated demonstration of a QTc interval > 500msec; long QT syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes (disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, bepridil, amiodarone, arsenic trioxide, cisapride, lidoflazine, clarithromycin, erythromycin, halofantrine, pentamidine, sparfloxacin, domperidone, droperidol, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide & methadone) Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, a condition requiring anti-arrythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry Patients may not be receiving any other investigational agents Patients with known brain metastases should be excluded from this clinical trial History of allergic reactions attributed to sulfonamides, arginine and compounds of similar chemical or biologic composition to PXD101 Patients should not have taken valproic acid, another histone deacytelase inhibitor, for at least 2 weeks prior to enrollment Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients with bowel obstruction would not be eligible because of compromised functional status unless they are on parenteral support Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PXD101 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Oza
Organizational Affiliation
University Health Network Princess Margaret Cancer Center P2C
Official's Role
Principal Investigator
Facility Information:
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Odette Cancer Centre- Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
University Health Network Princess Margaret Cancer Center P2C
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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