FLOT3: Prospective Study With FLOT in Patients With Locally Advanced, Limited Metastatic or Extensive Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

Sponsor

Krankenhaus Nordwest (Other)

Overall Status

Completed

CT.gov ID

NCT00849615

Collaborator

(none)

252

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with locally advanced or metastatic gastric carcinoma or carcinoma of the esophagogastric junction without prior palliative therapy will be treated with 8 cycles of the FLOT scheme (up to 12 cycles if the response is favourable). Prior to enrollment a unique and detailed clinical evaluation of the dissemination of the disease will be done which includes a differentiated regard of the metastatic status. patients will be classified as having either (A) locally advanced, (B) limited metastatic, or (C) extensive metastatic disease. In arms A and B surgical intervention is planned if operability is reached. The hypothesis is that by classifying patients more individually by the state of their disease, patients in arm B will have a significantly prolonged overall survival compared to patients in arm C.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Adenocarcinoma of the Esophagogastric Junction	Drug: Docetaxel Drug: 5-Fluorouracil Drug: Oxaliplatin Drug: folinic acid	Phase 2

Detailed Description

250 patients with locally advanced or metastatic gastric carcinoma or carcinoma of the esophagogastric junction without prior palliative therapy will be treated with 8 cycles of the FLOT scheme (up to 12 cycles if the response is favourable). Prior to enrolment a unique and detailed clinical evaluation of the dissemination of the disease will be done which includes a differentiated regard of the M-category in the TNM classification. A prospective stratification will classify the patients as having either (A) locally advanced, (B) limited metastatic, or (C) extensive metastatic disease. In addition, the pharmacogenetic risk profile of the patients will be evaluated by a combined analysis of two genetic polymorphisms of the metabolism of the applied substances (XPD312, GSTT1). For the assessment of the disease, reference regions are examined by CT or MRI scans and if applicable endoscopy prior to the start of the study, every 2 months during and after the end of therapy until progression of the disease occurs. Evaluation of quality of life (by standard forms like EORTC-Q30 and others) is continued after progression. Clinical examinations (blood count, assessment of toxicity, anamnesis) is performed every two weeks for evaluation of toxicity and application of chemotherapy. After informed consent is given, peripheral blood of the patient will be analysed for the pharmacogenetic risk profile. Representative tumor material will be analysed by immunohistochemistry and quantitative PCR for the expression of several molecular factors.

Study Design

Study Type:

Interventional

Actual Enrollment :

252 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective Multicenter Study With 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) in Patients With Locally Advanced, Limited Metastatic or Extensive Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FLOT	Drug: Docetaxel 50mg/m2 qd15 Drug: 5-Fluorouracil 2600mg/m2 qd15 Drug: Oxaliplatin 85mg/m2 qd15 Drug: folinic acid 200mg/m2 qd15

Arm

Intervention/Treatment

Experimental: FLOT

Drug: Docetaxel

50mg/m2 qd15

Drug: 5-Fluorouracil

2600mg/m2 qd15

Drug: Oxaliplatin

85mg/m2 qd15

Drug: folinic acid

200mg/m2 qd15

Outcome Measures

Primary Outcome Measures

overall survival [every 2 weeks during study, every 3 months follow-up]

Secondary Outcome Measures

Pharmacogenetic risk profile [once at beginning]
Quality of Life [every 8 weeks]
Progression free survival (PFS) and response rate (Stratum B and C) [every 8 weeks]
rate of R0-resections, rate of pathological remissions and perioperative morbidity and mortality in stratum A and B Perioperative Morbidität und Mortalität in dem Arm A und ggf. B [after surgical intervention]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Metastatic or locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction
No prior chemotherapy in metastatic state
Adequate blood and biochemistry parameters