A Randomized Study of GEMOX With or Without Cetuximab in Locally Advanced and Metastatic BTC

NCT ID: NCT01267344

Last Updated: 2016-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2015-05-31

Brief Summary

The primary objective is to investigate the objective response rate in patients receiving GEMOX (gemcitabine plus oxaliplatin) plus cetuximab as first line treatment in advanced or metastatic unresectable BTC biliary tract cancer compared to patients receiving the same chemotherapy without cetuximab. The secondary objectives include the exploration of the effect of the multimodality strategy on progression-free and overall survival, biomarker prediction, and toxicity.

Detailed Description

It is considered realistic, that within 18 months 120 patients can be included in the participating centers. Based on the previous publications an objective response rate (ORR) of 20% is expected in the GEMOX arm (Arm B). When the sample size of evaluable patients is between 110 and 120 evaluable patients (ie. 55 to 60 patients per treatment arm), then a two-sided 95% confidence interval (CI) for the difference between an arm B response rate PB, of 20% and an arm A response rate PA of 30%, 35% or 40% based on the large sample normal approximation will have a width between 15.4% and 16.7%. We assume an objective response rate of 30% for Arm A, then a two-sided 95% confidence interval (CI) for the difference between an arm B response rate PB, of 20% and an arm A response rate PA of 30% will have a width ±15.4% when the sample size of evaluable patients is 120 (i.e., 60 patients per treatment arm).

Conditions

Cholangiocarcinoma; Adenocarcinoma of Gallbladder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GEMOX

Intravenous infusion of gemcitabine 800 mg/m2 at a fixed rate of 10 mg/m2/min followed by oxaliplatin 85 mg/m2 2-hour infusion, every 2 weeks.

Group Type: ACTIVE_COMPARATOR

gemcitabine, oxaliplatin

Intervention Type: DRUG

GEMOX (intravenous infusion of gemcitabine 800 mg/m2 at a fixed rate of 10 mg/m2/min followed by oxaliplatin 85 mg/m2 2-hour infusion, every 2 weeks

E-GEMOX

Arm A will receive E-GEMOX with additional intravenous infusion of cetuximab (120 minutes for the 1st, 90 minutes for the 2nd and 60 minutes for all subsequent infusions) before GEMOX will be administered as above.

Group Type: EXPERIMENTAL

cetuximab, gemcitabine, oxaliplatin

Intervention Type: DRUG

E-GEMOX: intravenous infusion of cetuximab (120 minutes for the 1st, 90 minutes for the 2nd and 60 minutes for all subsequent infusions) before GEMOX will be administered as above. All of the study medication will be administrated on day 1 every 2 weeks, which is regarded as one cycle.

Interventions

gemcitabine, oxaliplatin

GEMOX (intravenous infusion of gemcitabine 800 mg/m2 at a fixed rate of 10 mg/m2/min followed by oxaliplatin 85 mg/m2 2-hour infusion, every 2 weeks

Intervention Type: DRUG

cetuximab, gemcitabine, oxaliplatin

E-GEMOX: intravenous infusion of cetuximab (120 minutes for the 1st, 90 minutes for the 2nd and 60 minutes for all subsequent infusions) before GEMOX will be administered as above. All of the study medication will be administrated on day 1 every 2 weeks, which is regarded as one cycle.

Intervention Type: DRUG

Other Intervention Names

Gemmis, Eloxatin; Erbitux@, Eloxatin

Eligibility Criteria

Inclusion Criteria

• Cyto-/histological confirmed unresectable, locally advanced, or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma or adenocarcinoma of gallbladder, but NOT other peri-ampulla Vateri or mixed tumor.
• At least one, not previously irradiated, measurable lesion according to RECIST (version 1.1).
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
• Aged no less than 20 years, at the time of acquisition of informed consent.
• Life expectancy >= 3 months.
• Adequate organ and bone marrow function as defined below: WBC >= 3.00 × 103/L and absolute neutrophil count >= 1.50 × 103/L, Platelet count >= 100 × 103/L, Hemoglobin level >= 10 g/dL, Serum creatinine <= 1.5 x Upper Normal Limit (UNL) and calculated GFR >= 40mL/min, Serum bilirubin <= 1.5 x UNL , ALT <= 2.5x UNL.
• Ability to understand and willingness to sign written Informed Consent Form.

Exclusion Criteria

• Other anti-tumor agent such as systemic chemotherapy, immunotherapy or EGFR/VEGF-pathway-targeting therapy before the commencement of study treatment.
• Radiotherapy (except palliative irradiation of bone lesions) within 4 weeks before the commencement of study treatment.
• Other cancer or prior treatment for other carcinomas within the last five years, except cured non-melanoma skin cancer and treated in-situ cervical cancer.
• Known CNS metastasis.
• Major surgery within 4 weeks prior to start of study treatment (diagnostic biopsy, laparotomy, line placement is not considered as major surgery).
• Pre-existing peripheral neuropathy >= grade 2.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in the past 12 months, active gastrointestinal bleeding, central nervous system disorders or psychiatric illness/social situation that would limit compliance with study requirements or judged to be ineligible for the study by the investigator.
• Having received any investigational agents or participated in any investigational drug study within 4 weeks prior to study enrollment.
• Pregnant or breast-feeding female (a pregnancy test must be performed on all female patients who are of child-bearing potential before entering the study, and the result must be negative).
• Poor compliance.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: collaborator

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: collaborator

Mackay Memorial Hospital

OTHER

Sponsor Role: collaborator

Tri-Service General Hospital

OTHER

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: collaborator

Taichung Veterans General Hospital

OTHER

Sponsor Role: collaborator

China Medical University Hospital

OTHER

Sponsor Role: collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role: collaborator

Kaohsiung Medical University

OTHER

Sponsor Role: collaborator

Kaohsiung Veterans General Hospital.

OTHER

Sponsor Role: collaborator

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Tz Chen, PHD

Role: STUDY_CHAIR

National Institute of Cancer Research

Tsang Wu Liu, MD

Role: STUDY_DIRECTOR

National Institute of Cancer Research, TCOG

Locations

National Institute of Cancer Research, Taiwan Cooperative Oncology Group

Zhunan, Miaoli County, Taiwan

Countries

Taiwan

References

Chen JS, Hsu C, Chiang NJ, Tsai CS, Tsou HH, Huang SF, Bai LY, Chang IC, Shiah HS, Ho CL, Yen CJ, Lee KD, Chiu CF, Rau KM, Yu MS, Yang Y, Hsieh RK, Chang JY, Shan YS, Chao Y, Chen LT; Taiwan Cooperative Oncology Group. A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer. Ann Oncol. 2015 May;26(5):943-949. doi: 10.1093/annonc/mdv035. Epub 2015 Jan 28.

Reference Type: DERIVED

PMID: 25632066 (View on PubMed)

Other Identifiers

T1210

Identifier Type: -

Identifier Source: org_study_id