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

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ClinicalTrials.gov Identifier: NCT00064259
Recruitment Status : Terminated (Discontinued development of G3139 (oblimersen))
First Posted : July 9, 2003
Results First Posted : June 29, 2015
Last Update Posted : June 29, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE July 8, 2003
First Posted Date  ICMJE July 9, 2003
Results First Submitted Date  ICMJE June 10, 2015
Results First Posted Date  ICMJE June 29, 2015
Last Update Posted Date June 29, 2015
Study Start Date  ICMJE June 2003
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00064259 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2013)
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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer
Official Title  ICMJE A Phase I/II Study of Oblimersen in Combination With Cisplatin and Fluorouracil in Patients With Advanced Esophageal, Gastro-Esophageal Junction and Gastric Cancer
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Biological: oblimersen sodium
    Given IV
    Other Names:
    • augmerosen
    • G3139
    • G3139 bcl-2 antisense oligodeoxynucleotide
    • Genasense
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: fluorouracil
    Given IV
    Other Names:
    • 5-fluorouracil
    • 5-Fluracil
    • 5-FU
Study Arms  ICMJE 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.

Interventions:
  • Biological: oblimersen sodium
  • Drug: cisplatin
  • Drug: fluorouracil
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 10, 2015)
15
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE February 2010
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00064259
Other Study ID Numbers  ICMJE NCI-2012-03134
02-66 ( Other Identifier: Montefiore Medical Center )
N01CM62204 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andreas Kaubisch Montefiore Medical Center
PRS Account National Cancer Institute (NCI)
Verification Date May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP