search
Back to results

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

Primary Purpose

Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bryostatin 1
cisplatin
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 Cancer

Eligibility Criteria

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

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)

Sites / Locations

  • City of Hope

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (bryostatin 1, cisplatin)

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall survival
Progression-free survival
Time to progression

Secondary Outcome Measures

Response rate (CR or PR)
Exact 95% confidence intervals will be calculated.
Time to treatment failure
Estimated using the product-limit method of Kaplan and Meier.
Duration of response
Estimated using the product-limit method of Kaplan and Meier.
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
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.

Full Information

First Posted
December 6, 2000
Last Updated
August 23, 2013
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00006942
Brief Title
Bryostatin 1 and Cisplatin in Treating Patients With Advanced Recurrent or Residual Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
Official Title
A Phase II Trial of Bryostatin in Combination With Cisplatin in Patients With Recurrent or Persistent Epithelial Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
October 2000 (undefined)
Primary Completion Date
March 2004 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial 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 (bryostatin 1, cisplatin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
bryostatin 1
Other Intervention Name(s)
B705008K112, BRYO, Bryostatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Overall survival
Time Frame
Time from first day of treatment to time of death due to any cause, assessed up to 9 years
Title
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
Title
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
Secondary Outcome Measure Information:
Title
Response rate (CR or PR)
Description
Exact 95% confidence intervals will be calculated.
Time Frame
Up to 9 years
Title
Time to treatment failure
Description
Estimated using the product-limit method of Kaplan and Meier.
Time Frame
Up to 9 years
Title
Duration of response
Description
Estimated using the product-limit method of Kaplan and Meier.
Time Frame
Up to 9 years
Title
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
Title
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Description
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.
Time Frame
Prior to initiation of chemotherapy
Title
Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not)
Description
Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used.
Time Frame
Day 5 of course 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Morgan
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs