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A Phase I/II Study of Genasense (G3139) in Combination With Cisplatin and Fluorouracil in Patients With Advanced Esophageal, Gastro-Esophageal Junction and Gastric Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00064259
First received: July 8, 2003
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
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 IIIA Esophageal Cancer
Stage IIIA Gastric Cancer
Stage IIIB Esophageal Cancer
Stage IIIB Gastric Cancer
Stage IIIC Esophageal Cancer
Stage IIIC Gastric Cancer
Stage IV Esophageal Cancer
Stage IV Gastric Cancer
Biological: oblimersen sodium
Other: laboratory biomarker analysis
Drug: cisplatin
Drug: fluorouracil
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Genasense (G3139) in Combination With Cisplatin and Fluorouracil in Patients With Advanced Esophageal, Gastro-Esophageal Junction and Gastric Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD of oblimersen sodium/Cisplatin [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Microarray data [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    This will be primarily descriptive, and will seek to compare patterns of gene expression pre- and post-treatment.


Enrollment: 97
Study Start Date: June 2003
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Other: laboratory biomarker analysis
Correlative studies
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have 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, as these have traditionally been grouped and treated the same as adenocarcinomas of the esophagus; patients must have locally advanced, recurrent or metastatic disease, not amenable to complete surgical resection or definitive radiation therapy
  • Patients participating in any portion of the study are not required to have measurable disease; clinically evaluable disease will suffice; the radiographic imaging required for study entry must be obtained within 3 weeks prior to start of therapy
  • Patients may have had prior surgery, radiation therapy, combined modality chemo- radiation, or at most one prior chemotherapy regimen for advanced, recurrent or metastatic disease; for patients who have received significant full dose chemotherapy (defined as at least 2 months of therapy) during their primary treatment (i.e. McDonald for adjuvant treatment of gastric cancer, or Herscovic for chemo- radiation of esophageal cancer) this will be considered a prior regimen of chemotherapy, unless at least 6 months have elapsed since completion of this treatment; if recurrence or progression occurs after 6 months from prior significant chemotherapy, another chemotherapeutic regimen may have been used prior to study entry; at least 3 weeks since the last administration of prior chemotherapy or radiation must have elapsed prior to commencing treatment on this study; 6 weeks if the last regimen included BCNU or mitomycin C; for patients on a weekly treatment regimen (e.g. weekly cisplatin/ irinotecan, weekly irinotecan/ PS341, weekly taxanes) patients may start treatment on protocol 2 weeks after the last dose of prior chemotherapy; for patients on treatment regimens given every 3 weeks, three weeks must have elapsed prior to initiating treatment on this protocol; hematologic recovery must be documented as outlined below
  • 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
  • The effects of G3139 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because G3139 agents as well as other therapeutic agents used in this trial are known to be teratogenic, 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 and for the duration of study participation; 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064259

Locations
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
Investigators
Principal Investigator: Andreas Kaubisch Montefiore Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00064259     History of Changes
Other Study ID Numbers: NCI-2012-03134, 02-66, N01CM62204
Study First Received: July 8, 2003
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Squamous Cell
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Stomach Diseases
Cisplatin
Fluorouracil
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014