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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

Phase 1/Phase 2
19 Years
Not Enrolling
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

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Trial Information

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


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.


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.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of oblimersen sodium/Cisplatin

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Andreas Kaubisch

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2003

Completion Date:

Related Keywords:

  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Stomach Neoplasms



Montefiore Medical Center Bronx, New York  10467-2490