Oblimersen and Gemcitabine in Treating Patients With Advanced Solid Tumor or Lymphoma

January 24, 2013 updated by: National Cancer Institute (NCI)

A Phase I Study of Oblimersen (Genasense™, G3139) in Combination With Gemcitabine in Advanced Malignancies

Drugs used in chemotherapy such as gemcitabine use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of gemcitabine by making cancer cells more sensitive to the drug. This phase I trial is studying the side effects and best dose of oblimersen and gemcitabine in treating patients with metastatic or unresectable solid tumors or lymphoma

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of oblimersen and gemcitabine in patients with advanced solid tumor or lymphoma.

II. Determine the effect of oblimersen on the pharmacokinetics and pharmacodynamics of gemcitabine in these patients.

III. Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oblimersen IV continuously on days 1-5 and gemcitabine IV over 2-3 hours on day 5. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen and gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 additional patients receive treatment at the MTD.

PROJECTED ACCRUAL: Approximately 15 patients will be accrued for this study within 6-8 months.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Histologically confirmed malignancy for which there is no standard or effective curative or palliative therapy

    • Solid tumors and lymphoma allowed
    • Metastatic or unresectable disease

  • Measurable or evaluable nonmeasurable disease

    • Evaluable nonmeasurable disease includes ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, abdominal masses not followed by CT scan or MRI, or cystic lesions
    • Disease characterized by elevated serum tumor marker alone is allowed
  • No known brain metastases
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 3 months
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 mg/dL
  • AST and ALT no greater than 2.5 times upper limit of normal
  • No history of portal hypertension
  • No history of cirrhosis or hepatitis
  • No radiographic evidence of cirrhosis and/or varices
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior allergic reaction attributed to compounds of similar chemical or biological composition to oblimersen or other study agents
  • No other concurrent uncontrolled illness that would preclude study participation
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No concurrent prophylactic colony-stimulating factors such as filgrastim (G-CSF) or sargramostim (GM-CSF)

  • Concurrent interventional growth factors allowed

    • No growth factor administration within 24 hours before study chemotherapy
  • Concurrent epoetin alfa allowed
  • No more than 3 prior chemotherapy regimens
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • More than 2 weeks since prior hormonal therapy
  • Concurrent megestrol for anorexia/cachexia allowed
  • No prior pelvic or whole abdominal radiotherapy
  • More than 4 weeks since prior radiotherapy
  • More than 4 weeks since prior major surgery
  • Recovered from prior therapy
  • More than 4 weeks since prior investigational therapy
  • No prior oblimersen
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (oblimersen sodium and gemcitabine hydrochloride)
Patients receive oblimersen IV continuously on days 1-5 and gemcitabine IV over 2-3 hours on day 5. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Correlative studies
Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • Gemzar
  • gemcitabine
  • dFdC
  • difluorodeoxycytidine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MTD defined as the dose level at which less than 2 out of 6 patients experience DLT assessed using NCI CTC version 2.0
Time Frame: 4 weeks
Descriptive statistics will be employed in the analysis of all safety and laboratory observations.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics
Time Frame: Pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 121.67, 126, and 129 hours
Peak concentration and area under the concentration time curves of gemcitabine triphosphate will be will be utilized to assess the pharmacodynamic relationship of gemcitabine triphosphate concentration to bivariate toxicity and tumor responses using logistic regression analysis.
Pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 121.67, 126, and 129 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Branimir (Brandy) Sikic, Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2003

Primary Completion (ACTUAL)

December 1, 2009

Study Registration Dates

First Submitted

May 6, 2003

First Submitted That Met QC Criteria

May 6, 2003

First Posted (ESTIMATE)

May 7, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

January 25, 2013

Last Update Submitted That Met QC Criteria

January 24, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02531
  • SUMC-78808
  • CDR0000299507 (REGISTRY: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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