Rebeccamycin Analog and Cisplatin With or Without Filgrastim in Treating Patients With Advanced Cancer

NCT ID: NCT00004189

Last Updated: 2013-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-10-31

Brief Summary

Phase I trial to study the effectiveness of rebeccamycin analog and cisplatin with or without filgrastim in treating patients who have advanced 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. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated doses of a rebeccamycin analogue and cisplatin with or without filgrastim (G-CSF) in patients with advanced malignancies.

II. Determine the qualitative and quantitative toxicities of these regimens in these patients.

III. Determine if the pharmacokinetics of a rebeccamycin analogue are affected by cisplatin and if there are sequence dependent pharmacokinetic effects.

IV. Assess any antitumor effects of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study of a rebeccamycin analogue and cisplatin.

Part I (previously untreated or minimally pretreated patients): The first patient of each cohort receives cisplatin IV over 1 hour followed 2 hours later by a rebeccamycin analogue IV over 1 hour on day 1. The second patient in the same cohort receives the same drugs in the reverse order. The drug sequence for each additional patient within the same cohort is alternated with reference to the preceding patient. During each subsequent course, the study drugs are administered to each patient in the reverse order as compared to the prior course. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Dose escalation is initially performed without filgrastim (G-CSF). Cohorts of 4-6 patients receive escalating doses of a rebeccamycin analogue and cisplatin until the maximum tolerated dose (MTD) of each drug is determined. The MTD is defined as the highest dose at which less than 2 of 6 patients experience dose limiting toxicity (DLT). If 2 of the first 6 patients experience DLT, then dose escalation proceeds in combination with G-CSF treatment. Patients receive G-CSF subcutaneously daily beginning on day 2 and continuing until blood counts have recovered for 2 days or until approximately day 15. Cohorts of 4-6 patients receive escalating doses of a rebeccamycin analogue and cisplatin as above. The MTD is defined as above.

Part II (heavily pretreated patients): Heavily pretreated patients receive a rebeccamycin analogue and cisplatin starting at 2 dose levels preceding the MTD from part I.

Patients are followed for at least 30 days.

Conditions

Lymphoma; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

See detailed description.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

becatecarin

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

Interventions

filgrastim

Intervention Type: BIOLOGICAL

becatecarin

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Prior radiotherapy to wide ports involving the pelvis or at least 25% of bone marrow
• Greater than 6 courses of prior combination chemotherapy including alkylating agent
• Prior nitrosoureas or mitomycin
• Widespread bone metastases with bone marrow involvement by bone marrow biopsy (positive bilateral bone marrow biopsy for lymphoma patients)
• Part II: Heavily pretreated as defined above
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• SWOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Hemoglobin greater than 9 mg/dL
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL

Renal:

• Creatinine less than 1.5 mg/dL

Cardiovascular:

• No uncontrolled hypertension
• No angina pectoris
• No clinically significant, multifocal, uncontrolled cardiac dysrhythmias

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active serious infection
• No clinically severe peripheral neuropathy (grade 1 or worse)
• No nonmalignant medical condition that would preclude compliance or increase risk of participation in study
• No hypersensitivity to E. coli derived drug preparations

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No other concurrent colony stimulating factors for prophylactic purposes

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks since prior nitrosoureas and mitomycin) and recovered

Endocrine therapy:

• No chronic oral corticosteroids
• No concurrent corticosteroids except as prophylactic antiemetic

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered

Other:

• At least 1 month since prior investigational agent
• No prophylactic oral or IV antibiotics for neutropenia unless fever present
• No other concurrent anticancer treatment or investigational agent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa Hammond, MD

Role: STUDY_CHAIR

The University of Texas Health Science Center at San Antonio

Locations

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Cancer Therapy and Research Center

San Antonio, Texas, United States

St. Luke's Lutheran Hospital

San Antonio, Texas, United States

Countries

United States

Other Identifiers

UTHSC-IDD-98-34

Identifier Type: -

Identifier Source: secondary_id

SACI-IDD-98-34

Identifier Type: -

Identifier Source: secondary_id

NCI-T98-0069

Identifier Type: -

Identifier Source: secondary_id

CDR0000067430

Identifier Type: -

Identifier Source: org_study_id