Combination Chemotherapy Plus Oblimersen in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00054548

Last Updated: 2013-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-10-31

Brief Summary

Phase I trial to study the effectiveness of combining carboplatin and paclitaxel with oblimersen in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of carboplatin and paclitaxel by making tumor cells more sensitive to the drugs.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of G3139 in combination with carboplatin and paclitaxel.

II. To determine the quantitative and qualitative nature of toxicities of G3139 with carboplatin and paclitaxel.

III. To measure G3139 activity in peripheral blood lymphocytes by quantitating Bcl-2/Bax expression and transcription, as well as T-cell functioning and signaling.

IV. To measure G3139 activity in tumor biopsy specimens by quantitating Bcl-2/Bax expression and transcription.

V. To determine the pharmacokinetics of carboplatin, paclitaxel, and G3139, as well as intratumoral G3139 levels.

VI. To screen various signal transduction pathways that may be affected by Bcl-2 down-regulation in PBMC and tumor biopsy specimens in order to better understand the mechanism of G3139 chemosensitization.

VII. To seek preliminary evidence of antitumor activity for the combination of G3139, carboplatin, and paclitaxel.

OUTLINE: This is a dose-escalation study of oblimersen.

Patients receive oblimersen IV continuously on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

An additional cohort of 12-15 patients receives treatment as above with oblimersen at the MTD.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

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

Study Groups

Treatment (oblimersen sodium, paclitaxel)

Patients receive oblimersen IV continuously on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

An additional cohort of 12-15 patients receives treatment as above with oblimersen at the MTD.

Group Type: EXPERIMENTAL

oblimersen sodium

Intervention Type: BIOLOGICAL

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

oblimersen sodium

Given IV

Intervention Type: BIOLOGICAL

paclitaxel

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; Anzatax; Asotax; TAX; Taxol; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically confirmed solid malignancy that is metastatic or unresectable and for which no standard curative therapy exists; patients with lymphoma are excluded
• ECOG performance status 0, 1, or 2 (Karnofsky >= 60%)
• Life expectancy of greater than 3 months
• Leukocytes >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelets >= 100,000/mm^3
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for three months after discontinuation of treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Patients will need to have a central line or nurse-placed PICC line in place prior to treatment on the protocol

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases will be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to G3139 or other agents used in study, unless approved by investigator
• No pre-existing grade >= 2 neuropathy
• No personal history of a bleeding diathesis given potential significant antiplatelet effects of therapy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with G3139
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study

• 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

George Wilding

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

CO 02904

Identifier Type: -

Identifier Source: secondary_id

NCI-5912

Identifier Type: -

Identifier Source: secondary_id

WCCC-CO-02904

Identifier Type: -

Identifier Source: secondary_id

U01CA062491

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2013-00010

Identifier Type: -

Identifier Source: org_study_id