Study of Cetuximab Plus P-HDFL for the First-Line Treatment of Advanced Gastric Cancer

NCT00384878 | Unknown Phase 2

• 1 other identifier: FEMH-95011
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The primary end point of the study is confirmed objective response rate (complete response \[CR\] and partial response \[PR\]). A response rate of 80 percent for cetuximab plus cisplatin and weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin (P-HDFL) chemotherapy is assumed. The Simon two-stage design will be used for P1 - P0 = 0.20. The response rates of interest are P0 = 60% and P1 = 80%. The investigators will reject cetuximab plus P-HDFL chemotherapy if the response rate is 8/13 at the first stage, and will reject the cetuximab plus P-HDFL chemotherapy if the response rate is 25/35 at the second stage. If there are more than 8 responses in 13 patients in the first stage, the study will continue to a total of 35 patients in the second stage. If there are more than 25 responses in 35 patients in the second stage, this treatment will be acceptable with a p-value of 0.05 and of 0.20. Evaluable patients for response will be those who received at least 4 doses of cetuximab (i.e. one cycle of protocol treatment). All enrolled patients will be subjected to toxicity evaluations. The primary end point of the study is confirmed objective response rates (by RECIST, Response Evaluation Criteria in Solid Tumors). The secondary end points of the study are progression-free survival, overall survival, and treatment-related toxicities. The analysis of response to treatment will be restricted to the eligible patients with at least one measurable lesion. The safety analysis will be restricted to the patients who received at least one cycle of the administered chemotherapy. The time-to-event end points will be estimated using the method of Kaplan and Meier and based on the intent-to-treat principle. Overall survival will be defined as the time interval between the date of study entry and the date of death. Progression-free survival will be defined as the time interval between the date of study entry and the date of disease progression or death, whichever occurred first. Duration of response will be defined as the time interval between the date of initial objective response and the date of disease progression, which is only for responders. If the event is not yet observed at the time of the last record, the patient will be censored at that time point.

Conditions

Stomach Neoplasms

Outcome Measures

Primary Outcomes (1)

• The primary end point of the study is confirmed objective response rates (by RECIST, Response Evaluation Criteria in Solid Tumors).

Secondary Outcomes (1)

• The secondary end points of the study are progression-free survival, overall survival, and treatment-related toxicities.

Interventions

Cetuximab, Cisplatin,5-Fluorouracil,Leucovorin DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years
• Histologically proven adenocarcinoma of the stomach that is nonresectable, locally advanced, or recurrent/metastatic
• At least one measurable lesion (by RECIST, Response Evaluation Criteria in Solid Tumors), and no prior radiotherapy to the target measurable lesion
• No prior chemotherapy for gastric cancer, but post-gastrectomy adjuvant therapy with low-dose 5-FU \[e.g., 5-FU 450 mg/m2 per week\] completed more than 6 months before study enrollment is acceptable
• World Health Organization (WHO) performance status 2
• Adequate baseline organ functions (checked within one week before entry into this study), defined as WBC count 3,000 cells/µL with neutrophils ≥ 1,500 cells/µL, platelet count 100,000 cells/µL, hemoglobin 9 g/dL, serum total bilirubin level 1.5 X UNLs (upper normal limits), serum AST and ALT 2.5 X ULNs (or serum AST and ALT 5.0 X ULNs for patients with liver metastases), serum creatinine level 1.5 X UNLs, 24-hour urine CCr 60 ml/min
• Fasting serum triglyceride level \> 70 mg/dL, which should be checked within one week before entry into this study. The lower limit for fasting serum triglyceride (70 mg/dL) is set to avoid HDFL-related hyperammonemic encephalopathy, which occurs in around 5% of Taiwanese patients.
• Written informed consent
• At least one month from gastrectomy, in case gastrectomy was performed; at least 2 weeks from laparotomy without resection, in case laparotomy was performed to document nonresectable status
• Availability of tumor sample for retrospective testing of EGFR (pharmacogenomic mutation analysis and immunohistochemical staining).

You may not qualify if:

• Concomitant anti-cancer biological agents, chemotherapy, or radiotherapy other than indicated in this protocol
• CNS metastasis
• Pregnant women, breast-feeding women, and women of child-bearing potential or fertile men without adequate contraception
• Life expectancy less than 3 months
• Serious concomitant illness or significant dysfunction of major organ systems which prohibit chemotherapy, such as:
• symptomatic heart disease, including significant arrhythmias, congestive heart failure or myocardial infarction within 12 months.
• extensive liver disease.
• major active infection.
• severe symptomatic pulmonary disease.
• Concurrent or prior second malignancy (except curatively resected cervical carcinoma in situ or squamous cell carcinoma of skin).
• Known hypersensitivity reaction to any of the components of study treatments.
• Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent
• Significant diseases, in the investigator's opinion, which would exclude the patient from the study.
• Legal incapacity or limited legal capacity.

Sponsors & Collaborators

• Far Eastern Memorial Hospital: lead

Study Sites (1)

Kun Huei Yeh, Ph.D

Taipei, Ban-Ciao, 220, Taiwan

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Cetuximab; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes

Study Officials

• Kun Huei Yeh, Ph.D.

  Far Eastern Memorial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kun Huei Yeh, Ph.D.

CONTACT

886-2-89667000; khyeh@mail.femh.org.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 4, 2006
• First Posted: October 6, 2006
• Study Start: June 1, 2006
• Primary Completion: March 1, 2007
• Last Updated: February 9, 2009

Record last verified: 2006-06

Locations

TW (1)