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Biliary Cancers: EGFR INhibitor, Gemcitabine and Oxaliplatin

Primary Purpose

Advanced Biliary Cancer

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Gemox, Cetuximab
Sponsored by
Gustave Roussy, Cancer Campus, Grand Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Biliary Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adenocarcinoma of the biliary tract (gallbladder, intra and/or extrahepatic bile ducts, or ampulla of Vater):

    • Cytologically or histologically confirmed. In case of uncertain biliary tract origin (e.g., intrahepatic, peripheral cholangiocarcinomas), inclusion is possible if i) extensive search for primary (thoracic and abdominopelvic CT scan, colonoscopy, upper digestive endoscopy, serum PSA level for men or mammography for women, and FDG-PET if possible) is negative; and ii) histological examination is consistent with bile duct adenocarcinoma (IHC should ideally be performed and be consistent with biliary primary, e.g., positive for cytokeratin 7 and 19 and negative for cytokeratin 20).
    • not amenable to curative resection, or recurrent after resection (i.e., locally advanced or metastatic),
    • With at least one unidimensionally measurable target lesion in a non-irradiated, non-PDT-treated area (longest diameter 1 cm [spiral CT scan]), or 2 cm [conventional CT scan]).
    • With biliary obstruction controlled,
  2. Age between 18 and 75 years.
  3. World Health Organization (WHO) performance status of 0 or 1.
  4. Life expectancy higher than 3 months.
  5. No prior chemotherapy for advanced disease. Previous adjuvant chemotherapy is allowed (completed at least 6 months previously, if containing gemcitabine or platinum salts). Previous irradiation (external radiotherapy, brachytherapy) and PDT are allowed provided that there is at least one unidimensionally measurable target lesion in untreated area.
  6. Bilirubin 3 times the upper limit of the normal range (ULN). Pts with jaundice or evidence of bile duct obstruction, in whom the biliary tree can be decompressed by endoscopic or percutaneous endoprothesis with subsequent reduction in bilirubin £ 3 ULN, will be eligible for the study.
  7. Aminotransferases (AST, ALT) 5 ULN, INR < 1.5 (following vitamin K1 injection in patients with current or recent history of jaundice or bile duct obstruction), creatinine 1.5 ULN, neutrophils 1.5 109/L, platelets 100 109/L, hemoglobin 9 g/dL (red blood cell transfusion if needed is allowed).
  8. Written informed consent. Note: EGFR tumor status has to be known for every pt, but it is neither an inclusion/exclusion criterion nor a stratification factor. EGFR expression has to be assessed by IHC using biopsy or surgical material, at any time prior to inclusion into the study.

Exclusion Criteria:

  1. Known central nervous system metastases.
  2. Contraindication or history of grade 3-4 allergy reaction to one treatment component.
  3. Surgery (except diagnostic biopsy), external radiotherapy, brachytherapy, or PDT within 30 days prior to start of treatment. Prior adjuvant chemotherapy is only allowed if completed at least 30 days previously (6 months if containing gemcitabine or platinum salts).
  4. Participation in another clinical trial within 30 days prior to start of treatment.
  5. Concomitant systemic chronic immunotherapy, chemotherapy, or antitumor hormone therapy.
  6. Previous administration of EGFR inhibitors or EGF.
  7. Active uncontrolled infection, peripheral neuropathy grade 2, acute or subacute bowel obstruction or history of inflammatory bowel disease, symptomatic coronary disease or myocardial infarction in the past 6 months, congestive heart failure (NYHA class II), interstitial pneumonitis or respiratory failure, or renal failure.
  8. Pregnancy (or positive b-HCG dosage at baseline), breast-feeding, or lack of effective contraception in male or female pts of reproductive potential.
  9. Other malignancies either currently active or in the last 5 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell skin carcinoma.
  10. Legal incapacity or physical, psychological or mental status interfering with the pt's ability to terminate the study or to sign the informed consent.

Sites / Locations

  • Institut Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

1

2

Arm Description

GEMOX

GEMOX + CETUXIMAB

Outcomes

Primary Outcome Measures

Evaluation of treatment efficacy by assessing the crude progression-free survival (PFS) rate at 4 months

Secondary Outcome Measures

Evaluation of feasibility and toxicity of the treatments
Evaluation of rate and duration of objective tumor response
Evaluation of rate and duration of tumor control (objective responses and stabilizations)
Evaluation of PFS and over

Full Information

First Posted
October 31, 2007
Last Updated
June 12, 2012
Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
Merck Serono International SA
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1. Study Identification

Unique Protocol Identification Number
NCT00552149
Brief Title
Biliary Cancers: EGFR INhibitor, Gemcitabine and Oxaliplatin
Official Title
A Multicenter, Randomized Phase II Trial Assessing the Activity of Gemcitabine - Oxaliplatin Chemotherapy Alone or in Combination With Cetuximab in Patients With Advanced Biliary Cancer.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2007
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
Merck Serono International SA

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A Multicenter, Randomized Phase II Trial Assessing the Activity of Gemcitabine - Oxaliplatin Chemotherapy Alone or in Combination with Cetuximab in Patients with Advanced Biliary Cancer.
Detailed Description
The BINGO trial is an open-label randomized phase II study evaluating the efficacy and tolerance of gemcitabine-oxaliplatin combination chemotherapy (GEMOX regimen) alone or in combination with cetuximab in patients (pts) with ABC. The BINGO study also comprises ancillary translational research and functional imaging studies which aim to identify markers predictive for treatment efficacy in ABC. All eligible pts will be randomized 1:1 to receive: Arm A: GEMOX alone every two weeks. Arm B: GEMOX + cetuximab every two weeks. Randomization will be stratified according to: tumor stage (locally advanced vs metastatic), primary tumor location (gallbladder vs non-gallbladder), prior treatments (surgery or radiotherapy or brachytherapy or photodynamic therapy [PDT] or adjuvant chemotherapy vs none), center. EGFR tumor status has to be assessed for every pt by immunohistochemistry (IHC) using biopsy or surgical material, at any time prior to inclusion into the study, but it is neither an inclusion/exclusion criterion nor a stratification factor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Biliary Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
GEMOX
Arm Title
2
Arm Type
Experimental
Arm Description
GEMOX + CETUXIMAB
Intervention Type
Drug
Intervention Name(s)
Gemox, Cetuximab
Intervention Description
GEMOX (Arms 1 and 2), every two weeks: Day 1: gemcitabine 1000 mg/m² intravenous (IV) infusion over 100 minutes (10 mg/m²/min) Day 2: oxaliplatin 100 mg/m² IV infusion over 2 h Cetuximab (ErbituxÒ) (Arm B only) every two weeks: (chemotherapy will be started one hour after the end of the cetuximab infusion). Day 1 or Day 2: 500 mg/m² IV infusion over 150 minutes
Primary Outcome Measure Information:
Title
Evaluation of treatment efficacy by assessing the crude progression-free survival (PFS) rate at 4 months
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Evaluation of feasibility and toxicity of the treatments
Time Frame
one year
Title
Evaluation of rate and duration of objective tumor response
Time Frame
one year
Title
Evaluation of rate and duration of tumor control (objective responses and stabilizations)
Time Frame
one year
Title
Evaluation of PFS and over
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adenocarcinoma of the biliary tract (gallbladder, intra and/or extrahepatic bile ducts, or ampulla of Vater): Cytologically or histologically confirmed. In case of uncertain biliary tract origin (e.g., intrahepatic, peripheral cholangiocarcinomas), inclusion is possible if i) extensive search for primary (thoracic and abdominopelvic CT scan, colonoscopy, upper digestive endoscopy, serum PSA level for men or mammography for women, and FDG-PET if possible) is negative; and ii) histological examination is consistent with bile duct adenocarcinoma (IHC should ideally be performed and be consistent with biliary primary, e.g., positive for cytokeratin 7 and 19 and negative for cytokeratin 20). not amenable to curative resection, or recurrent after resection (i.e., locally advanced or metastatic), With at least one unidimensionally measurable target lesion in a non-irradiated, non-PDT-treated area (longest diameter 1 cm [spiral CT scan]), or 2 cm [conventional CT scan]). With biliary obstruction controlled, Age between 18 and 75 years. World Health Organization (WHO) performance status of 0 or 1. Life expectancy higher than 3 months. No prior chemotherapy for advanced disease. Previous adjuvant chemotherapy is allowed (completed at least 6 months previously, if containing gemcitabine or platinum salts). Previous irradiation (external radiotherapy, brachytherapy) and PDT are allowed provided that there is at least one unidimensionally measurable target lesion in untreated area. Bilirubin 3 times the upper limit of the normal range (ULN). Pts with jaundice or evidence of bile duct obstruction, in whom the biliary tree can be decompressed by endoscopic or percutaneous endoprothesis with subsequent reduction in bilirubin £ 3 ULN, will be eligible for the study. Aminotransferases (AST, ALT) 5 ULN, INR < 1.5 (following vitamin K1 injection in patients with current or recent history of jaundice or bile duct obstruction), creatinine 1.5 ULN, neutrophils 1.5 109/L, platelets 100 109/L, hemoglobin 9 g/dL (red blood cell transfusion if needed is allowed). Written informed consent. Note: EGFR tumor status has to be known for every pt, but it is neither an inclusion/exclusion criterion nor a stratification factor. EGFR expression has to be assessed by IHC using biopsy or surgical material, at any time prior to inclusion into the study. Exclusion Criteria: Known central nervous system metastases. Contraindication or history of grade 3-4 allergy reaction to one treatment component. Surgery (except diagnostic biopsy), external radiotherapy, brachytherapy, or PDT within 30 days prior to start of treatment. Prior adjuvant chemotherapy is only allowed if completed at least 30 days previously (6 months if containing gemcitabine or platinum salts). Participation in another clinical trial within 30 days prior to start of treatment. Concomitant systemic chronic immunotherapy, chemotherapy, or antitumor hormone therapy. Previous administration of EGFR inhibitors or EGF. Active uncontrolled infection, peripheral neuropathy grade 2, acute or subacute bowel obstruction or history of inflammatory bowel disease, symptomatic coronary disease or myocardial infarction in the past 6 months, congestive heart failure (NYHA class II), interstitial pneumonitis or respiratory failure, or renal failure. Pregnancy (or positive b-HCG dosage at baseline), breast-feeding, or lack of effective contraception in male or female pts of reproductive potential. Other malignancies either currently active or in the last 5 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell skin carcinoma. Legal incapacity or physical, psychological or mental status interfering with the pt's ability to terminate the study or to sign the informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David MALKA, MD
Organizational Affiliation
Gustave Roussy, Cancer Campus, Grand Paris
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
24852116
Citation
Malka D, Cervera P, Foulon S, Trarbach T, de la Fouchardiere C, Boucher E, Fartoux L, Faivre S, Blanc JF, Viret F, Assenat E, Seufferlein T, Herrmann T, Grenier J, Hammel P, Dollinger M, Andre T, Hahn P, Heinemann V, Rousseau V, Ducreux M, Pignon JP, Wendum D, Rosmorduc O, Greten TF; BINGO investigators. Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Lancet Oncol. 2014 Jul;15(8):819-28. doi: 10.1016/S1470-2045(14)70212-8. Epub 2014 May 19.
Results Reference
derived

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Biliary Cancers: EGFR INhibitor, Gemcitabine and Oxaliplatin

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