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

NCT ID: NCT00849615

Last Updated: 2016-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2016-01-31

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.

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.

Conditions

Gastric Cancer; Adenocarcinoma of the Esophagogastric Junction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FLOT

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

50mg/m2 qd15

5-Fluorouracil

Intervention Type: DRUG

2600mg/m2 qd15

Oxaliplatin

Intervention Type: DRUG

85mg/m2 qd15

folinic acid

Intervention Type: DRUG

200mg/m2 qd15

Interventions

Docetaxel

50mg/m2 qd15

Intervention Type: DRUG

5-Fluorouracil

2600mg/m2 qd15

Intervention Type: DRUG

Oxaliplatin

85mg/m2 qd15

Intervention Type: DRUG

folinic acid

200mg/m2 qd15

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Krankenhaus Nordwest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Salah Al-Batan, MD

Role: STUDY_CHAIR

Institute of Clinical Cancer Research IKF, UCT - University Cancer Center, Frankfurt, Germany

Locations

Krankenhaus Nordwest

Frankfurt, , Germany

Countries

Germany

References

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, Jager 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.

Reference Type: BACKGROUND

PMID: 18349393 (View on PubMed)

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, Jager 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.

Reference Type: BACKGROUND

PMID: 18669868 (View on PubMed)

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. doi: 10.1200/JCO.2004.07.042.

Reference Type: BACKGROUND

PMID: 14966088 (View on PubMed)

Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, Schmalenberg H, Luley KB, Prasnikar N, Egger M, Probst S, Messmann H, Moehler M, Fischbach W, Hartmann JT, Mayer F, Hoffkes HG, Koenigsmann M, Arnold D, Kraus TW, Grimm K, Berkhoff S, Post S, Jager E, Bechstein W, Ronellenfitsch U, Monig S, Hofheinz RD. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017 Sep 1;3(9):1237-1244. doi: 10.1001/jamaoncol.2017.0515.

Reference Type: DERIVED

PMID: 28448662 (View on PubMed)

Other Identifiers

S396 FLOT3

Identifier Type: -

Identifier Source: org_study_id