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A Phase I Study of Antisense Bcl-2 Oligonucleotide (G3139) in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Antisense Bcl-2 Oligonucleotide (G3139) in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumors


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

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

Type of Study:


Study Design:

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

Outcome Measure:

Maximum tolerated dose (MTD) defined as the highest safely tolerated dose where at most 1 patient experiences a dose-limiting toxicities (DLT) and the next higher dose having at least 2 patients who experience DLT

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

George Wilding

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Wisconsin Hospital and Clinics


United States: Food and Drug Administration

Study ID:




Start Date:

October 2002

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001