Vaccine Therapy Plus Chemotherapy in Treating Patients With Metastatic or Locally Recurrent Stomach Cancer or Esophageal Cancer

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00020787

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining vaccine therapy and chemotherapy in treating patients who have metastatic or locally recurrent stomach cancer or esophageal cancer.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer Gastric Cancer	Biological: G17DT Immunogen Drug: cisplatin Drug: fluorouracil	Phase 3

Detailed Description

OBJECTIVES: I. Determine a safe and immunogenic combination of G17DT with cisplatin and fluorouracil in patients with chemotherapy-naive metastatic or locally recurrent gastric or gastroesophageal cancer. II. Determine the safety profile and tolerability of this regimen in these patients. III. Determine the tumor response rate, disease stabilization, best overall response, time to progression, time to treatment failure, and overall survival in patients treated with this regimen. IV. Determine the correlation of immunological response with clinical efficacy and benefit in patients treated with this regimen. V. Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are assigned to one of four treatment regimens. Regimen A: Patients receive high-dose G17DT intramuscularly (IM) on days 7, 35, and 63. Patients also receive cisplatin IV over 1-3 hours on day 1 followed by fluorouracil IV continuously over days 1-5 every 4 weeks in the absence of disease progression or unacceptable toxicity. If inadequate immune response is seen on Regimen A, subsequent patients are treated on Regimen B. If unacceptable toxicity is seen on Regimen A, subsequent patients are treated on Regimen C. If inadequate immune response and unacceptable toxicity are seen on Regimen A, or if unacceptable toxicity is seen on Regimen B or inadequate immune response is seen on Regimen C, then subsequent patients are treated on Regimen D. Regimen B: Patients receive high-dose G17DT IM on days 1, 28, and 56. Patients also receive cisplatin IV over 1-3 hours on day 35 followed by fluorouracil IV continuously over days 35-39 every four weeks in the absence of disease progression or unacceptable toxicity. Regimen C: Patients receive low-dose G17DT IM on days 7, 35, and 63 with chemotherapy as in regimen A. Regimen D: Patients receive low-dose G17DT IM on days 1, 28, and 56 with chemotherapy as in regimen B. Quality of life is assessed at baseline, on day 7, every 2 weeks for 10 weeks, and then every 4 weeks thereafter.

PROJECTED ACCRUAL: A total of 15-75 patients will be accrued for this study within 5-30 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label, Sequential Multi-Center Multi Dose Study Of G17T Immunogen In Combination With Cisplatin (CDDP) And 5-Fluorouracil (5-FU) In Subjects With Metastatic Or Locally Recurrent Gastric Or Gastroesophageal Cancer Previously Untreated With Chemotherapy For Advanced Disease (Stage IV)

Study Start Date :

Jul 1, 2001

Actual Primary Completion Date :

Jan 1, 2002

Actual Study Completion Date :

Dec 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment See intervention description.	Biological: G17DT Immunogen Dose: 500 micrograms in 0.2mL Route: Deep intramuscular Schedule: Days 8, 36, and 64; an additional dose at week 2, cycle 7 will be administered Drug: cisplatin dose: 100 mg/m2 Route: i.v. infusion in 500 mL in 0.9% NaCl administered up to 3 hours Schedule: day 1, and then every 4 weeks. Other Names: cisplatinum cis-diamminedichloroplatinum(II) Drug: fluorouracil Dose: 1000mg/m2/day Route: 24-hour continuous infusion in 0.9% NaCl over 5 days Schedule: Day 1 to Day 5 (5-day infusion) and then every 4 weeks Other Names: 5-FU

Arm

Intervention/Treatment

Experimental: Treatment

See intervention description.

Biological: G17DT Immunogen

Dose: 500 micrograms in 0.2mL Route: Deep intramuscular Schedule: Days 8, 36, and 64; an additional dose at week 2, cycle 7 will be administered

Drug: cisplatin

dose: 100 mg/m2 Route: i.v. infusion in 500 mL in 0.9% NaCl administered up to 3 hours Schedule: day 1, and then every 4 weeks.

Other Names:

cisplatinum

cis-diamminedichloroplatinum(II)

Drug: fluorouracil

Dose: 1000mg/m2/day Route: 24-hour continuous infusion in 0.9% NaCl over 5 days Schedule: Day 1 to Day 5 (5-day infusion) and then every 4 weeks

Other Names:

5-FU

Outcome Measures

Primary Outcome Measures

To determine whether a concomitant G17DT-chemotherapy regimen affects tumor response in subjects with gastric or gastroesophageal cancer. [6 months to 1 year]

Secondary Outcome Measures

Time to disease progression, best overall response, and survival will be evaluated in the intent-to-treat population and the evaluable population. [6 months to 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent.
Gastric adenocarcinoma, including adenocarcinoma of the esophagogastric junction, histologically proven.
Measureable metastatic disease.
Male or female subjects, age 18 years and older.
Karnofsky performance status score equal to or greater than 70.
Life expectancy of at least 3 months.
Subjects must be chemotherapy naïve.
At least 6 weeks from prior curative radiotherapy and 3 weeks from surgery.
Adequate hematological and coagulation parameters: hemoglobin>9.5 g/dL; white blood cell count>3x10^{9/L, platelets> 100x10}9/L; international normalized ratio of prothrombin time <1.2, and activated partial thromboplastin time no more than 5 seconds above normal limits.
Adequate clinical chemistry parameters: creatinine<1.5mg/dL; total bilirubin<1.5mg/dL; and aspartate aminotransferase and alanine aminotransferase <2.5x upper normal levels.
Able to comply with scheduled follow-up and with management of toxicity.
Use contraceptive measures, if sexually active

Exclusion Criteria:

Previous or current malignancies other than gastric adenocarcinoma, with the exception of adequately treated in situ carcinoma of the cervix, uteri, or nonmelanoma skin cancer
Female subjects who are pregnant or nursing
Female subjects with reproductive potential refusing a pregnancy test
Any previous palliative chemotherapy, adjuvant or neoadjuvant chemotherapy, or investigational drug
Any prior anticancer immunotherapy
Immunodeficiency
Bone marrow transplantation within 1 year
Symptomatic peripheral neuropathy > Grade 2 NCI-CTC, Version 2.0 criteria
Severe hearing disorder > Grade 2 NCI-CTC, Version 2.0 criteria
Known dihydropyrimidine dehydrogenase deficiency
Any other sever condition as defined by the following: unstable cardiac disease despite treatment; myocardial infarction within 6 months before study entry; history of significant neurologic or psychiatric disorders including dementia or seizures; active uncontrolled infection; active disseminated intravascular coagulation; or any other serious underlying medical conditions that could impair the ability of the subject to participate in the study
Subjects who have previously demonstrated hypersensitivity to diphtheria toxoid
Subjects who require chronic administration of corticosteroids
Use in the past 30 days or concomitant use of immunosuppressants
Use in the past 14 days or chronic concomitant use of proton pump inhibitors
Subjects who have a history of hypercalcemia
Subjects who cannot be regularly followed up for psychological, social, familial, or geographic reasons
Subjects with expected noncompliance to toxicity management