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

NCT ID: NCT00020787

Last Updated: 2020-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-07-31
• Study Completion Date: 2002-12-31

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.

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.

Conditions

Esophageal Cancer; Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

See intervention description.

Group Type: EXPERIMENTAL

G17DT Immunogen

Intervention Type: BIOLOGICAL

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

cisplatin

Intervention Type: DRUG

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.

fluorouracil

Intervention Type: DRUG

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

Interventions

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

Intervention Type: BIOLOGICAL

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.

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

cisplatinum; cis-diamminedichloroplatinum(II); 5-FU

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

UCLA

Principal Investigators

Joel R. Hecht, MD

Role: STUDY_CHAIR

Jonsson Comprehensive Cancer Center

Locations

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Countries

United States

References

Ajani JA, Hecht JR, Ho L, Baker J, Oortgiesen M, Eduljee A, Michaeli D. An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer: the GC4 study. Cancer. 2006 May 1;106(9):1908-16. doi: 10.1002/cncr.21814.

Reference Type: RESULT

PMID: 16568451 (View on PubMed)

Hecht JR, Ajani JA, Michaeli D: A multicenter phase II study of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination with G17DT immunogen in patients with locally recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction previously untreated for advanced disease. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1035, 258, 2003.

Reference Type: RESULT

Other Identifiers

UCLA-0006040

Identifier Type: -

Identifier Source: secondary_id

APHTON-BB-IND-8737

Identifier Type: -

Identifier Source: secondary_id

NCI-G01-1959

Identifier Type: -

Identifier Source: secondary_id

UCLA-GC4C

Identifier Type: -

Identifier Source: secondary_id

CDR0000068713

Identifier Type: -

Identifier Source: org_study_id