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

A Phase 2 Study of PXD101 in Platinum Resistant Epithelial Ovarian Tumors and Micropapillary/Borderline (LMP) Ovarian Tumors

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Ovarian Carcinoma; Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Stage IV Ovarian Cancer; Stage III Ovarian Cancer; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Belinostat

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre- Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network Princess Margaret Cancer Center P2C

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Belinostat; Given IV; Other Names: PXD101; Beleodaq; PXD 101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Disease Progression (Epithelial Ovarian Cancer Group)	Assessed by RECIST criteria. Summarized using summary statistics, such as the mean, median, counts and proportion.	Up to 5 years
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.	Up to 5 years
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.	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
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.	Duration of time from start of treatment to time of progression, assessed up to 5 years
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.	Up to 5 years
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.	Up to 5 years
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.	Up to 5 years
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.	Up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship Between Clinical and Pharmacodynamic Effects of Belinostat in Patients With Platinum Resistant and Micropapillary/ Borderline Ovarian Tumors	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.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amit Oza, University Health Network Princess Margaret Cancer Center P2C

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 9, 2006
• First Submitted That Met QC Criteria: March 9, 2006
• First Posted (Estimate): March 13, 2006

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: July 20, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Neoplasms, Fibroepithelial; Neoplasms; Carcinoma; Recurrence; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Brenner Tumor; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Belinostat
• Other Study ID Numbers: NCI-2009-00144 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62203 (U.S. NIH Grant/Contract); N01CM17107 (U.S. NIH Grant/Contract); 7267 (Other Identifier: CTEP); PMH-PHL-041; CDR0000459798; NCI-7267; PHL-041 (Other Identifier: University Health Network Princess Margaret Cancer Center P2C)