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

Gastric Cancer Clinical Trial

— FLOT3  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00849615
• Other study ID #: S396 FLOT3
• Status: Completed
• Phase: Phase 2
• First received: February 23, 2009
• Last updated: April 5, 2016
• Start date: February 2009
• Est. completion date: January 2016

Study information

• Verified date: April 2016
• Source: Krankenhaus Nordwest
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: January 2016
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Exclusion Criteria:

• Hypersensitivity for 5-FU, Leucovorin, Oxaliplatin or Docetaxel

• KHK, cardiomyopathy or cardiac insufficiency

• Malignancy <5 years ago

• Brain metastases

• Severe internal disease or inadequate blood and biochemistry parameters

• Pregnancy and lactation

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Esophagogastric Junction
• Esophageal Neoplasms
• Gastric Cancer

Intervention

Drug:
• Docetaxel
50mg/m2 qd15
• 5-Fluorouracil
2600mg/m2 qd15
• Oxaliplatin
85mg/m2 qd15
• folinic acid
200mg/m2 qd15

Locations

Country	Name	City	State
Germany	Krankenhaus Nordwest	Frankfurt

Sponsors (1)

Lead Sponsor	Collaborator
Krankenhaus Nordwest

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Al-Batran SE, Atmaca A, Hegewisch-Becker S, Jaeger D, Hahnfeld S, Rummel MJ, Seipelt G, Rost A, Orth J, Knuth A, Jaeger E. Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol. 2004 Feb 15;22(4):658-63. — View Citation

Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. doi: 10.1093/annonc/mdn403. Epub 2008 Jul 31. — View Citation

Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. doi: 10.1200/JCO.2007.13.9378. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		every 2 weeks during study, every 3 months follow-up	No
Secondary	Pharmacogenetic risk profile		once at beginning	No
Secondary	Quality of Life		every 8 weeks	No
Secondary	Progression free survival (PFS) and response rate (Stratum B and C)		every 8 weeks	No
Secondary	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	No