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

Fallopian Tube Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006942
• Other study ID #: NCI-2012-02831
• Secondary ID: NCI-2012-02831PH
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2000
• Last updated: August 23, 2013
• Start date: October 2000

Study information

• Verified date: August 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. primary completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer
• Recurrent Ovarian Epithelial Cancer
• Stage III Ovarian Epithelial Cancer
• Stage IV Ovarian Epithelial Cancer

Intervention

Drug:
• bryostatin 1
Given IV
• cisplatin
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		Time from first day of treatment to time of death due to any cause, assessed up to 9 years	No
Primary	Progression-free survival		Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 9 years	No
Primary	Time to progression		Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 9 years	No
Secondary	Response rate (CR or PR)	Exact 95% confidence intervals will be calculated.	Up to 9 years	No
Secondary	Time to treatment failure	Estimated using the product-limit method of Kaplan and Meier.	Up to 9 years	No
Secondary	Duration of response	Estimated using the product-limit method of Kaplan and Meier.	Up to 9 years	No
Secondary	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		Up to 9 years	Yes
Secondary	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.	Prior to initiation of chemotherapy	No
Secondary	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.	Day 5 of course 2	No