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

  • STATUS
    Recruiting
  • End date
    Aug 26, 2022
  • participants needed
    506
  • sponsor
    Federation Francophone de Cancerologie Digestive
Updated on 26 January 2021

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.

Details
Condition OESOPHAGO-GASTRIC CARCINOMA, OESOPHAGO-GASTRIC CARCINOMA, OESOPHAGO-GASTRIC CARCINOMA, OESOPHAGO-GASTRIC CARCINOMA, OESOPHAGO-GASTRIC CARCINOMA, OESOPHAGO-GASTRIC CARCINOMA
Treatment docetaxel, Oxaliplatin, Folinic Acid, 5Fluorouracil bolus, 5Fluorouracil continu
Clinical Study IdentifierNCT03006432
SponsorFederation Francophone de Cancerologie Digestive
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have OESOPHAGO-GASTRIC CARCINOMA?
Do you have any of these conditions: Do you have OESOPHAGO-GASTRIC CARCINOMA??
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 ( 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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note