Combination Chemotherapy and Oblimersen in Treating Patients With Advanced Colorectal Cancer - Full Text View

Sponsor:	San Antonio Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00055822

Purpose

RATIONALE: 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. Oblimersen may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs.

PURPOSE: Phase I/II trial to study the effectiveness of combining oxaliplatin, fluorouracil, and leucovorin with oblimersen in treating patients who have unresectable, metastatic, or recurrent colorectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Biological: oblimersen sodium Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study of Oblimersen Sodium (G3139, Genasense) in Combination With Oxaliplatin, 5FU and Leucovorin (FOLFOX4) Regimen in Advanced Colorectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Oblimersen sodium Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

October 2002

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of oblimersen when administered with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced colorectal cancer.
Determine the quantitative and qualitative toxic effects of this regimen in these patients.
Determine the antitumor activity of this regimen in these patients.
Determine the plasma pharmacokinetics of oblimersen and oxaliplatin in patients treated with this regimen.
Determine relevant predictive biomarkers of response in patients treated with this regimen.

OUTLINE: This is an open-label, phase I, dose-escalation study of oblimersen followed by a non-randomized, phase II study.

Phase I: Patients receive oblimersen IV continuously on days 1-5 and 15-19; leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 6, 7, 20, and 21; and oxaliplatin IV over 2 hours on days 6 and 20.

Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

Phase II: Up to 35 additional patients are treated as in phase I, with oblimersen at the MTD.

In both phases, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 6-53 patients (6-18 patients for phase I and 12-35 patients for phase II) will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
- Unresectable, metastatic, or recurrent disease
Measurable or evaluable disease (phase I)
Measurable disease (phase II)
No known brain metastases
- Patients with previously treated brain metastases who are not currently receiving steroids and have a stable CT scan or MRI are eligible

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

At least 12 weeks

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9 g/dL

Hepatic

Bilirubin no greater than 1.5 mg/dL
AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
INR no greater than 1.5 times ULN (unless currently receiving anticoagulant therapy)
PT/PTT no greater than 1.5 times ULN (unless currently receiving anticoagulant therapy)

Renal

Creatinine normal OR
Creatinine clearance at least 60 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of allergic reaction to compounds of similar chemical or biologic composition to fluorouracil or oxaliplatin
No other concurrent uncontrolled medical condition that would preclude study participation
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No known history of degenerative facet disease during prior fluorouracil therapy
No HIV-positive patients receiving combination antiretroviral therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent epoetin alfa during course 1
No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)
No concurrent immunotherapy

Chemotherapy

At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No prior oxaliplatin
No other concurrent chemotherapy

Endocrine therapy

See Disease Characteristics

Radiotherapy

At least 4 weeks since prior radiotherapy and recovered
No concurrent radiotherapy

Surgery

Not specified

Other

No prior oblimersen
No other concurrent investigational agents
No other concurrent antitumor therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00055822

Locations

United States, Texas
San Antonio Cancer Institute
San Antonio, Texas, United States, 78229-3264

Sponsors and Collaborators

San Antonio Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Anthony W. Tolcher, MD

San Antonio Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00055822 History of Changes
Other Study ID Numbers:	CDR0000271308, SACI-IDD-02-23, NCI-5793
Study First Received:	March 6, 2003
Last Updated:	April 4, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the colon
recurrent colon cancer
stage III colon cancer
stage IV colon cancer

adenocarcinoma of the rectum
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on February 12, 2012