A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer

NCT ID: NCT00064259

Last Updated: 2021-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2010-02-28

Brief Summary

Drugs used in chemotherapy such as cisplatin and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. This phase I/II trial is studying the side effects and best dose of oblimersen when given with cisplatin and fluorouracil and to see how well they work in treating patients with locally advanced, recurrent, or metastatic cancer of the esophagus, gastroesophageal junction, or stomach.

Detailed Description

PRIMARY OBJECTIVES:

I. The escalation portion of the study will determine the MTD of G3139/Cisplatin and will help determine the toxicities of this combination.

II. Once the MTD is determined, an additional 12 patients will be enrolled in order to obtain a set of tumor biopsies for microarray analysis.

SECONDARY OBJECTIVES:

I. The collection of additional toxicity data for this combination

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

Phase I: Patients receive oblimersen IV continuously on days 1-7, fluorouracil IV continuously on days 4-8, and cisplatin IV 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 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 12 patients are treated at the MTD.

Phase II: Patients receive treatment as in phase I with oblimersen at the MTD.

PROJECTED ACCRUAL: Approximately 37-97 patients (3-36 for phase I and 34-67 for phase II) will be accrued for this study within 15-18 months.

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

Study Design

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

Study Groups

Treatment (oblimersen sodium)

Phase I: Patients receive oblimersen IV continuously on days 1-7, fluorouracil IV continuously on days 4-8, and cisplatin IV 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 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 12 patients are treated at the MTD.

Phase II: Patients receive treatment as in phase I with oblimersen at the MTD.

Group Type: EXPERIMENTAL

oblimersen sodium

Intervention Type: BIOLOGICAL

Given IV

cisplatin

Intervention Type: DRUG

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

Interventions

oblimersen sodium

Given IV

Intervention Type: BIOLOGICAL

cisplatin

Given IV

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

Other Intervention Names

augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; CACP; CDDP; CPDD; DDP; 5-fluorouracil; 5-Fluracil; 5-FU

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the esophagus, gastro- esophageal junction, or stomach; patients with squamous cell carcinoma of the esophagus will also be eligible, patients must have locally advanced, recurrent or metastatic disease, not amenable to complete surgical resection or definitive radiation therapy
• Measurable and/or evaluable disease
• May have had prior surgery, radiation therapy, combined modality chemo- radiation, or at most one prior chemotherapy regimen for advanced, recurrent or metastatic disease;
• Life expectancy of greater than 12 weeks
• ECOG performance status =<2 (Karnofsky >= 60%)
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin within normal institutional limits
• Creatinine =< 1.5 OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Ability to understand and the willingness to sign a written informed consent document
• Patients with accessible tumors are obliged to participate in biopsies 1 and 2; accessible tumors are defined as tumors reachable by EGD, or metastases, which, in the opinion of the treating physician can be biopsied with commonly utilized biopsy methods (such as CT guided biopsy); biopsy #3 on day 6 is optional; patients who do not have have accessible tumor tissue may participate in the study if at least one tumor deposit is measurable

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 21 days (6 weeks for nitrosoureas or mitomycin C, two weeks if prior treatment was a weekly regimen) prior to entering the study or those who have not recovered from adverse events (grade 2 or worse) due to agents administered earlier
• Patients who have had photodynamic therapy within 4 weeks of proposed study entry will be excluded; patients will be allowed to receive concurrent photodynamic therapy for obstruction untreatable by stent, laser, or dilation; patients who do require concurrent photodynamic therapy and who are participating in the serial biopsy portion of the study must wait until after cycle 1 and its biopsies are completed
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to anti- sense oligonucleotides, cisplatin, fluorouracil or other agents used in the study
• Patients may not have received G3139 previously
• 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 because G3139 is an anti- sense oligonucleotide agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with G3139, breastfeeding should be discontinued if the mother is treated with G3139; these potential risks may also apply to other agents used in this study
• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with G3139 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas Kaubisch

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Locations

Montefiore Medical Center

The Bronx, New York, United States

Countries

United States

References

Raab R, Sparano JA, Ocean AJ, Christos P, Ramirez M, Vinciguerra V, Kaubisch A. A phase I trial of oblimersen sodium in combination with cisplatin and 5-fluorouracil in patients with advanced esophageal, gastroesophageal junction, and gastric carcinoma. Am J Clin Oncol. 2010 Feb;33(1):61-5. doi: 10.1097/COC.0b013e3181a31ad0.

Reference Type: RESULT

PMID: 19738454 (View on PubMed)

Other Identifiers

02-66

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62204

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-03134

Identifier Type: -

Identifier Source: org_study_id