Bryostatin 1 and Cisplatin in Treating Patients With Metastatic or Unresectable Stomach Cancer

A Phase II Combination Trial of Bryostatin-1 and Cisplatin in the Treatment of Metastatic Gastric Cancer

Phase II trial to study the effectiveness of bryostatin 1 and cisplatin in treating patients who have metastatic or unresectable stomach cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bryostatin 1 may increase the effectiveness of cisplatin by making tumor cells more sensitive to the drug. Combining cisplatin with bryostatin 1 may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Stage IV Gastric Cancer; Stage III Gastric Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cisplatin; Drug: bryostatin 1

Detailed Description

OBJECTIVES:

I. Determine the response rate and survival in patients with metastatic or unresectable carcinoma of the stomach treated with bryostatin 1 and cisplatin.

II. Determine the toxic effects of this regimen in these patients. III. Determine the molecular determinants of response to this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive bryostatin 1 IV over 72 hours on days 1-3 followed by cisplatin IV over 1 hour on day 4. Treatment repeats every 3 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033-0804
      • University of Southern California

Participation Criteria

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:

• Diagnosis of metastatic or unresectable carcinoma of the stomach
• Measurable disease
• No brain metastasis
• Performance status - Karnofsky 70-100%
• More than 3 months
• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL
• No history of any bleeding disorders
• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 2 times normal
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• No history of peptic ulceration or gastrointestinal bleeding
• No active infection
• No seizure disorder
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other serious concurrent illness that would preclude study entry
• No medical, social, or psychological factors that would preclude study entry
• No prior chemotherapy
• No prior radiotherapy
• More than 4 weeks since prior major surgery
• Prior incomplete resection allowed
• No other prior antitumor treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment; Patients receive bryostatin 1 IV over 72 hours on days 1-3 followed by cisplatin IV over 1 hour on day 4. Treatment repeats every 3 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.	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	Measure Description	Time Frame
Observed Response Rate.	All patients had measurable disease and were assessed after 2 cycles of chemotherapy by medical photograph, plain x-ray, CT, MRI or other imaging scans of at least 2.0 cm or greater with conventional techniques or 1.0 cm or greater with spiral CT. Patients were evaluated by RECIST criteria. All measurable lesions, up to 10 "target lesions" were recorded and measured at baseline across the longest diameter (LD). All other non-target lesions were documented as present or absent. Complete Response (CR) was defined as complete disappearance of the tumor, partial response (PR) was defined as at least a 30% decrease of the sum of the LD of the target lesions, using the baseline sum LD as the reference The observed response rate was defined as the percentage of evaluable patients whose best response is a CR or PR with associated 95% confidence interval.	Best response recorded from the start of treatment until disease progression/recurrence. Assessed every 2 cycles.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was estimated according to the Kaplan-Meier product-limit method.	18 months
Progression-free Survival	Progression-free survival was estimated according to the Kaplan-Meier product-limit method	18 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (ACTUAL): March 1, 2010
• Study Completion (ACTUAL): March 1, 2010

Study Registration Dates

• First Submitted: October 4, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 26, 2014
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Cisplatin; Bryostatin 1
• Other Study ID Numbers: NCI-2012-02361 (REGISTRY: CTRP (Clinical Trial Reporting Program)); N01CM17101 (U.S. NIH Grant/Contract); CHNMC-PHII-22; CDR0000068267; NCI-T99-0040; PHII-22 (USC 3S-00-1) (OTHER: University of Southern California); T99-0040 (OTHER: CTEP)