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PHASE III RANDOMISED TRIAL TO EVALUATE FOLFOX WITH OR WITHOUT DOCETAXEL (TFOX) AS 1st LINE CHEMOTHERAPY FOR LOCALLY ADVANCED OR METASTATIC OESOPHAGO-GASTRIC CARCINOMA (GASTFOX)

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ClinicalTrials.gov Identifier: NCT03006432
Recruitment Status : Recruiting
First Posted : December 30, 2016
Last Update Posted : October 14, 2020
Sponsor:
Collaborators:
UNICANCER
GERCOR - Multidisciplinary Oncology Cooperative Group
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive

Tracking Information
First Submitted Date  ICMJE December 27, 2016
First Posted Date  ICMJE December 30, 2016
Last Update Posted Date October 14, 2020
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 27, 2016)
progression-free survival [ Time Frame: 12 months after laste randomisation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 27, 2016)
  • Overall survival Toxicity events (adverse events) according to NCI-CTC v4.0 [ Time Frame: 12 months after laste randomisation ]
  • Objective response rate [ Time Frame: 12 months after laste randomisation ]
  • Toxicity events according to NCI-CTC v4.0 [ Time Frame: 12 months after laste randomisation ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PHASE III RANDOMISED TRIAL TO EVALUATE FOLFOX WITH OR WITHOUT DOCETAXEL (TFOX) AS 1st LINE CHEMOTHERAPY FOR LOCALLY ADVANCED OR METASTATIC OESOPHAGO-GASTRIC CARCINOMA
Official Title  ICMJE ESSAI DE PHASE III RANDOMISE EVALUANT LE FOLFOX AVEC OU SANS DOCETAXEL (TFOX) EN 1ère LIGNE DE CHIMIOTHERAPIE DES ADENOCARCINOMES OESO-GASTRIQUES LOCALEMENT AVANCES OU METASTATIQUES
Brief Summary

Gastric cancer is the fourth commonest cancer and the second largest cause of mortality from cancer. Surgical resection of localised forms of gastric cancer offers the only chance of a cure. The vast majority of patients, however, present with advanced disease from the outset (locally advanced or metastatic) or recurrent after resection of a localised form.

For metastatic or locally advanced stages of gastric or gastro-oesophageal junction adenocarcinoma, the combination of 2 chemotherapy drugs (dual therapy) as compared with monotherapy or no chemotherapy, makes it possible to improve the tumour response and patient survival. Dual therapy comprising cisplatin + fluoropyrimidine (CF protocol) is considered as one of the first-line chemotherapy treatment standards.

The addition of docetaxel to the CF regime (referred to as the DCF protocol) has made it possible to improve the tumour response rate, the time to tumour progression and overall survival in a randomised phase III trial. This improvement in treatment efficacy was achieved, however, at the expense of a significant increase in grade 3-4 toxicity, including diarrhoea , neutropenia, and neutropenia with complications. Although DCF is considered as a therapeutic standard for advanced forms of gastric cancer, its use is limited in clinical practice due to its high toxicity.

Oxaliplatin has shown its usefulness in treatment of oesophagogastric cancer, with an efficacy at least equal to that of cisplatin. Peripheral sensory neuropathy was less common in the 5FU-cisplatin arm. In terms of treatment efficacy, 5FU-oxaliplatin versus 5FU-cisplatin was associated with a non-significant improvement in median progression free survival rates, and overall survival.

All these data thus suggest that 5FU-oxaliplatin is at least as efficacious and is better tolerated than 5FU-cisplatin, and also that docetaxel-5FU-cisplatin is more efficacious than 5FU-cisplatin, with limited use due to its high toxicity. In the logical continuation of development of chemotherapy protocols for metastatic gastric cancer, the question therefore arises of the usefulness of adding docetaxel to 5FU-oxaliplatin, in terms of efficacy and also tolerance.

In France, chemotherapy with FOLFOX is used extensively as a first line of treatment in advanced gastric cancer, but with progression-free survival and median survival rates that are still too low, and a poor response rate. The use of docetaxel at a dose of 50 mg/m2 every 2 weeks in combination with FOLFOX (TFOX protocol) has shown very interesting results in phase II studies in terms of efficacy and tolerability, and these are worth confirming through a phase III randomised trial. In fact, if these results are confirmed in phase III, TFOX could become the new first-line therapeutic standard for advanced gastric cancer, while limiting toxicity and preserving patients' quality of life, and could become the reference treatment to accompany the targeted therapies currently being developed for this disease.

The primary objective of this randomised phase III trial is to compare the progression-free survival on dual therapy with 5FU-oxaliplatin (FOLFOX protocol) with triple therapy with 5FU-oxaliplatin-docetaxel (TFOX protocol) in treatment of advanced forms of gastric or oesophagogastric junction adenocarcinoma. The secondary objectives are overall survival, the tumour response rate, toxicity, quality of life and the therapeutic index, defined as the ratio between the median progression-free survival and the febrile neutropenia rate.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE OESOPHAGO-GASTRIC CARCINOMA
Intervention  ICMJE
  • Drug: Oxaliplatin
  • Drug: 5Fluorouracil bolus
  • Drug: 5Fluorouracil continu
  • Drug: Docetaxel
  • Drug: Folinic Acid
Study Arms  ICMJE
  • Active Comparator: FOLFOX
    Cycles every 15 days until progression desease
    Interventions:
    • Drug: Oxaliplatin
    • Drug: 5Fluorouracil bolus
    • Drug: 5Fluorouracil continu
    • Drug: Folinic Acid
  • Experimental: TFOX
    Cycles every 15 days until progression desease
    Interventions:
    • Drug: Oxaliplatin
    • Drug: 5Fluorouracil continu
    • Drug: Docetaxel
    • Drug: Folinic Acid
Publications * Zaanan A, Samalin E, Aparicio T, Bouche O, Laurent-Puig P, Manfredi S, Michel P, Monterymard C, Moreau M, Rougier P, Tougeron D, Taieb J, Louvet C. Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study). Dig Liver Dis. 2018 Apr;50(4):408-410. doi: 10.1016/j.dld.2018.01.119. Epub 2018 Mar 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 27, 2016)
506
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Gastric or gastro-oesophageal junction adenocarcinoma (all Siewert), histologically proven (on primary tumour or metastatic lesion),
  • HER2 negative (positive HER2 status is defined by a positive IHC test of 3+ or IHC of 2+ with positive FISH)
  • Metastatic or non-resectable (locally advanced) disease
  • Disease measurable according to RECIST v1.1 criteria (at least one measurable lesion)
  • No major surgical procedure during the 4 weeks prior to randomisation:
  • Patient eligible for a 1st line of chemotherapy based on 5FU, folinic acid and oxaliplatin (FOLFOX) with or without docetaxel (TFOX)
  • WHO: 0-1
  • Age ≥ 18
  • BMI > 18
  • Life expectancy > 3 months
  • PNN > 1500/mm3, platelets > 100,000/mm3, Hb > 10 g/dL
  • AST, ALT ≤ 3.5 times the UNL, alkaline phosphatase < 6 times the UNL
  • Bilirubin ≤ 1.5 times the UNL,
  • Creatinine clearance according to Cockcroft and Gault formula > 50 mL/min
  • Women of childbearing age must have a negative pregnancy test (β HCG) before starting treatment
  • Women of childbearing age and men (who are in a sexual relationship with women of childbearing age) must agree to use effective contraception without interruption for the duration of the treatment and for 6 months after administration of the last dose of treatment
  • Patient affiliated to a social security scheme
  • Patient information and signature of informed consent form

Exclusion Criteria:

  • Presence of cerebral or meningeal metastases
  • Presence of > grade 2 neuropathy according to NCIC-CTC 4.0
  • Known DPD deficiency
  • QT/QTc interval > 450 msec for men and > 470 msec for women
  • K+ < LNL, Mg2+ < LNL, Ca2+ < LNL
  • Any known specific contraindication or allergy to the treatments used in the study (cf RCP Appendix 7)
  • Chemotherapy or radio-chemotherapy in an adjuvant situation finished less than 12 months ago
  • Prior chemotherapy including oxaliplatin (except for adjuvant chemotherapy)
  • Prior chemotherapy including docetaxel
  • Any progressive pathology not stabilised over the past 6 months: liver impairment, renal impairment, respiratory or cardiac failure
  • HIV+ patients
  • Radiotherapy during the 4 weeks prior to randomisation
  • Other concomitant cancer or a history of cancer during the previous 5 years, with the exception of carcinoma in situ of the cervix or basal cell carcinoma or epidermoid cell carcinoma of the skin which is considered to be cured
  • Patient already included in another clinical trial involving an experimental drug
  • Pregnant or breastfeeding woman
  • Persons in custody or under wardship
  • Impossibility of undergoing medical monitoring during the trial for geographical, social or psychological reasons
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marie MOREAU +33 (0)380393404 marie.moreau@u-bourgogne.fr
Listed Location Countries  ICMJE France,   Martinique
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03006432
Other Study ID Numbers  ICMJE PRODIGE 51
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Federation Francophone de Cancerologie Digestive
Study Sponsor  ICMJE Federation Francophone de Cancerologie Digestive
Collaborators  ICMJE
  • UNICANCER
  • GERCOR - Multidisciplinary Oncology Cooperative Group
Investigators  ICMJE
Study Chair: Aziz ZAANAN HEGP, Paris
PRS Account Federation Francophone de Cancerologie Digestive
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP