Gemcitabine Hydrochloride and Oxaliplatin or Observation in Treating Patients With Biliary Tract Cancer That Has Been Removed by Surgery

Sponsor

UNICANCER (Other)

Overall Status

Completed

CT.gov ID

NCT01313377

Collaborator

(none)

190

Enrollment

Locations

Arms

Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Observation is watching a patient's condition but not giving treatment until symptoms appear. It is not yet known whether giving gemcitabine hydrochloride together with oxaliplatin is more effective than observation in treating patients with biliary tract cancer that has been removed by surgery.

PURPOSE: This randomized phase III trial is studying giving gemcitabine hydrochloride together with oxaliplatin to see how well it works compared with observation in treating patients with biliary tract cancer that has been removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Extrahepatic Bile Duct Cancer Gallbladder Cancer Liver Cancer	Drug: gemcitabine hydrochloride Drug: oxaliplatin Other: clinical observation Procedure: adjuvant therapy Procedure: quality-of-life assessment	Phase 3

Detailed Description

OBJECTIVES:

Primary

Compare disease-free survival (DFS) of patients with resected biliary tract cancer treated with adjuvant gemcitabine hydrochloride and oxaliplatin versus clinical observation.
Compare quality of life of these patients.

Secondary

Compare overall survival of these patients.
Determine the toxicity of the chemotherapy in these patients.
Explore prognostic factors for DFS including resection result (R0 vs R1), location of primary tumor (intrahepatic vs extrahepatic vs gallbladder), evolution of CA19-9, and lymph node involvement (N0 vs N+ and Nx). (Exploratory)
Study pathological factors in surgical specimens to identify main characteristics and phenotypic clinicoanatomical biliary tract cancers before therapy. (Exploratory)
Identify nontumor-associated liver injury and factors that may facilitate the emergence of biliary tract cancers. (Exploratory)
Identify signaling pathways that may predict response to therapy. (Exploratory)
Determine the molecular characteristics to differentiate tumors according to their position in the biliary tract (extrahepatic bile duct, intrahepatic cholangiocarcinoma site [hilar], and peripheral cholangiocarcinoma vesicle site). (Exploratory)

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 14 days for 12 courses.
Arm II: Patients undergo clinical observation only every 4 weeks for 5 months. Quality of life is assessed at baseline, at 3 and 6 months, and then at all follow-up visits.

After completion of study therapy, patients are followed up at 6 months, every 3 months for 2 years, and then every 6 months for 3 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

190 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Multicenter Randomized Study Comparing the Effect of Adjuvant Chemotherapy for Six Months With Gemcitabine-Oxaliplatin 85 mg/m2 (GEMOX 85) to Observation in Patients Who Underwent Surgery for Cancer of the Bile Ducts

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARM A: Gemox 85 Adjuvant chemotherapy for six months with gemcitabine - oxaliplatin 85mg / m² ( GEMOX 85)	Drug: gemcitabine hydrochloride Drug: oxaliplatin Procedure: adjuvant therapy Procedure: quality-of-life assessment
Other: ARM B: Observation until progression or death	Other: clinical observation Procedure: quality-of-life assessment

Arm

Intervention/Treatment

Experimental: ARM A: Gemox 85

Adjuvant chemotherapy for six months with gemcitabine - oxaliplatin 85mg / m² ( GEMOX 85)

Drug: gemcitabine hydrochloride

Drug: oxaliplatin

Procedure: adjuvant therapy

Procedure: quality-of-life assessment

Other: ARM B:

Observation until progression or death

Other: clinical observation

Procedure: quality-of-life assessment

Outcome Measures

Primary Outcome Measures

Disease-free survival [up to 3 years]
Quality of life [up to 3 years]

Secondary Outcome Measures

Overall survival [up to 3 years]
Toxicity of adjuvant chemotherapy [up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically proven adenocarcinoma of the intrahepatic bile ducts, gallbladder, or extrahepatic bile ducts
Mixed forms of hepatocholangiocarcinomas included provided the cholangiocarcinoma is predominant
Underwent surgical resection of the disease (R0 or R1) at least 4 weeks but no more than 13 weeks ago
Nonmetastatic disease as assessed by abdominal MRI and chest x-ray
No cancer of the pancreas or duodenum invading the bile duct and ampulla of Vater

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Hemoglobin ≥ 10 g/dL (transfusion allowed)
ANC ≥ 1,500/mm³
Platelet count ≥ 75,000/mm³
Creatinine clearance > 40 mL/min
Prothrombin time > 60% OR INR < 1.5 (without anticoagulant therapy)
Transaminases ≤ 5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN
Conjugated bilirubin ≤ 35 μmol/L (after biliary drainage, if necessary)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No contraindications to oxaliplatin and gemcitabine hydrochloride therapy
Prior invasive cancer allowed provided it has been in complete remission for ≥ 5 years
No other concurrent invasive cancer except adequately treated carcinoma in situ of the cervix or basal cell carcinoma
No other severe, unresolved disease
No mental illness
No HIV positivity
No grade 1 angina or symptomatic angina ≥ grade 2
No sensitive peripheral neuropathy
No uncontrolled diabetes
No inability to undergo medical tests due to geographical, social, or psychological reasons
No prisoners or patients under guardianship
No Child B or C cirrhosis

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior neoadjuvant chemotherapy or radiotherapy
No prior organ transplantation
No concurrent participation in another clinical trial of an experimental agent

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU - Hôpital Nord	Amiens	France	80054
2	Centre Paul Papin	Angers	France	49933
3	Institut Sainte Catherine	Avignon	France	84082
4	Centre hospitalier de la Côte Basque	Bayonne	France	64109
5	Hôpital Jean Minjoz	Besancon	France	25030
6	Hôpital Avicenne	Bobigny	France	93009
7	CHU Brest - Hôpital Morvan	Brest	France	29200
8	CHU Côte de Nacre	Caen	France	14000
9	CHU Estaing	Clermont Ferrand	France	63003
10	Hôpital Beaujon	Clichy	France	92118
11	Hôpital Henri Mondor	Créteil	France	94000
12	Hôpital Bocage	Dijon	France	21079
13	CHD Vendée	La Roche Sur Yon	France	85925
14	Centre Léon Bérard	Lyon	France	69008
15	Hôpital Privé Jean Mermoz	Lyon	France	69373
16	Hôpital Edouard Herriot	Lyon	France	69437
17	Hôpital Saint Joseph	Marseille	France	13008
18	Hôpital Nord	Marseille	France	13015
19	Institut Paoli Calmettes	Marseille	France	13273
20	CHU Timone Adulte	Marseille	France	13385
21	Centre Hospitalier Saint Eloi	Montpellier	France	34295
22	Centre René Gauducheau	Nantes	France	44805
23	Hôpital La Source	Orléans	France	45067
24	Hôpital Saint Antoine	Paris	France	75012
25	Institut Mutualiste Montsouris	Paris	France	75014
26	CHU Saint Louis	Paris	France	75475
27	Hôpital de la Pitié Salpétrière	Paris	France	75651
28	Hôpital Européen Georges Pompidou	Paris	France	75908
29	CHU de Poitiers	Poitiers	France	86021
30	Centre Eugene Marquis	Rennes	France	35042
31	CHU de Rouen - Hôpital Ch. Nicolle	Rouen	France	76031
32	CHU Sainte-Etienne - Hopital Nord	Sainte-Etienne	France	42255
33	Centre Paul Strauss	Strasbourg	France	67065
34	Hôpital de Hautepierre / Hôpital Civil	Strasbourg	France	67098
35	Hôpital Trousseau	Tours	France	37044
36	CHU Brabois	Vandouevre Les Nancy	France	54511
37	Institut Gustave Roussy	Villejuif	France	94800