Bryostatin 1 and Cisplatin in Treating Patients With Advanced Recurrent or Residual Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

August 23, 2013 updated by: National Cancer Institute (NCI)

A Phase II Trial of Bryostatin in Combination With Cisplatin in Patients With Recurrent or Persistent Epithelial Ovarian Cancer

Phase II trial to study the effectiveness of combining bryostatin 1 and cisplatin in treating patients who have advanced recurrent or residual ovarian epithelial, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the overall response rate and the complete response rate of patients with platinum-refractory ovarian cancer who are treated with infusional Bryostatin-1 given in combination with intravenous cisplatin.

II. To estimate the duration of response in these patients. III. To obtain tissue in order to evaluate the molecular determinants of apoptosis including: p53 status, WAF1/CIP1 gene expression prior to and directly after chemotherapy, bcl-2 gene expression in vivo, bcl-2/bax ratio, p21, and the extent of apoptosis determined by the TdT assay; and the molecular determinants of DNA damage and repair including: expression levels of ERCC1.

OUTLINE: This is a multicenter study.

Patients receive bryostatin 1 IV continuously over 72 hours immediately followed by cisplatin IV over 1 hour. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 18-32 patients will be accrued for this study within 2 years.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Advanced recurrent or residual ovarian, fallopian tube, or papillary primary peritoneal cancer which has been histologically confirmed
  • Eligible patients include patients with measurable disease who have progressed while on chemotherapeutic treatment, patients with biopsy-proven persistent, clinically-measurable disease with best response as stable at the completion of planned first-line therapy, patients with persistent or recurrent disease with rising CA-125 to levels at least twice normal; the CA-125 increase must be documented by two independent measurements; no patient may have received more than two prior regimens of chemotherapy including first-line treatment
  • Patients must have a Karnofsky performance status of greater than or equal to 50% and an estimated survival of at least three months
  • Measured or calculated clearance >= 60 ml/min
  • AGC >= 1800/mm^3
  • Plts >= 100,000/mm^3
  • Bilirubin =< 1.5 mg/dl
  • SGOT less than 2 x upper limit of normal
  • Previous radiotherapy or chemotherapy must have been completed at least three weeks before treatment under this protocol
  • Patients must have the ability to give voluntary informed consent and to comply with the treatment and required tests
  • Because Bryostatin is of unknown teratogenic potential, women of childbearing potential must have a negative pregnancy test and must take adequate precautions to prevent pregnancy during treatment
  • Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment, or is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible
  • Patients currently being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator
  • The extent of all evaluable and nonevaluable disease must be documented; pretreatment radiographic examinations should be done no earlier than 4 weeks (28 days) prior to the first course of chemotherapy; pre-treatment chemistries and CA-125 levels should be done no earlier than two weeks (14 days) prior to initiation of chemotherapy; (in calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on Monday, the Monday four weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (bryostatin 1, cisplatin)
Patients receive bryostatin 1 IV continuously over 72 hours immediately followed by cisplatin IV over 1 hour. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression.
Other: laboratory biomarker analysis
Correlative studies
Drug: cisplatin
Given IV
Other Names:
  • CDDP
  • DDP
  • CACP
  • CPDD
Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: Time from first day of treatment to time of death due to any cause, assessed up to 9 years
Time from first day of treatment to time of death due to any cause, assessed up to 9 years
Progression-free survival
Time Frame: Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 9 years
Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 9 years
Time to progression
Time Frame: Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 9 years
Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 9 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate (CR or PR)
Time Frame: Up to 9 years
Exact 95% confidence intervals will be calculated.
Up to 9 years
Time to treatment failure
Time Frame: Up to 9 years
Estimated using the product-limit method of Kaplan and Meier.
Up to 9 years
Duration of response
Time Frame: Up to 9 years
Estimated using the product-limit method of Kaplan and Meier.
Up to 9 years
Incidence by severity and type of toxicity based on the National Cancer Institute (NCI) Common Toxicity Criteria v2.0 and NCI Myalgia Toxicity Grading Scale
Time Frame: Up to 9 years
Up to 9 years
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Time Frame: Prior to initiation of chemotherapy
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.
Prior to initiation of chemotherapy
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Time Frame: Day 5 of course 2
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.
Day 5 of course 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Robert Morgan, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2000

Primary Completion (Actual)

March 1, 2004

Study Registration Dates

First Submitted

December 6, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

August 26, 2013

Last Update Submitted That Met QC Criteria

August 23, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02831 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • N01CM17101 (U.S. NIH Grant/Contract)
  • PHII-21 (Other Identifier: City of Hope)
  • T99-0039 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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