- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00064259
A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer
A Phase I/II Study of Oblimersen in Combination With Cisplatin and Fluorouracil in Patients With Advanced Esophageal, Gastro-Esophageal Junction and Gastric Cancer
Study Overview
Status
Conditions
- Adenocarcinoma of the Gastroesophageal Junction
- Stage IV Gastric Cancer
- Recurrent Gastric Cancer
- Squamous Cell Carcinoma of the Esophagus
- Adenocarcinoma of the Esophagus
- Recurrent Esophageal Cancer
- Stage IV Esophageal Cancer
- Diffuse Adenocarcinoma of the Stomach
- Intestinal Adenocarcinoma of the Stomach
- Mixed Adenocarcinoma of the Stomach
- Stage IIIA Gastric Cancer
- Stage IIIB Gastric Cancer
- Stage IIIC Gastric Cancer
- Stage III Esophageal Cancer
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
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New York
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Bronx, New York, United States, 10467-2490
- Montefiore Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
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)
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. |
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of Oblimersen in Combination With Cisplatin and 5-FU
Time Frame: 21 days
|
Adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria (version 2.0).
DLT was defined as grade 3 to 4 hematologic toxicity lasting more than 1 week after 5-FU/cisplatin, grade 3 to 4 nausea or vomiting occurring later than 11 days after cisplatin, grade 3 to 4 diarrhea occurring later than 10 days after 5-FU, and grade 3 to 4 mucositis at the beginning of the next cycle.
|
21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Microarray Data
Time Frame: Up to 12 weeks
|
This will be primarily descriptive, and will seek to compare patterns of gene expression pre- and post-treatment.
|
Up to 12 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Andreas Kaubisch, Montefiore Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Neoplasms, Squamous Cell
- Carcinoma, Squamous Cell
- Stomach Neoplasms
- Recurrence
- Adenocarcinoma
- Esophageal Neoplasms
- Esophageal Squamous Cell Carcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Cisplatin
- Fluorouracil
- Oblimersen
Other Study ID Numbers
- NCI-2012-03134
- N01CM62204 (U.S. NIH Grant/Contract)
- 02-66 (OTHER: Montefiore Medical Center)
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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