Overview

This trial is active, not recruiting.

Conditions adenocarcinoma of the gastroesophageal junction, adenocarcinoma of the stomach
Treatments 5-fu, leucovorin, docetaxel, oxaliplatin (flot), trastuzumab, post-operative treatment trastuzumab mono therapy
Phase phase 2
Sponsor AIO-Studien-gGmbH
Collaborator Roche Pharma AG
Start date December 2011
End date February 2015
Trial size 53 participants
Trial identifier NCT01472029, 2011-001507-13, AIO-STO-0310

Summary

The purpose of this study is to determine the rate of complete pathological responses (percentage of patients with pCR referring to the total number of enrolled and eligible patients), as evaluated centrally by a reference pathologist.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
5-fu, leucovorin, docetaxel, oxaliplatin (flot), trastuzumab
Pre-operative treatment 4 cycles and post-operative treatment 4 cycles: Trastuzumab 4 mg/kg BW (6 mg loading dose at 1st administration), iv over 1 h on day 1 of each 14 day cycle Docetaxel 50 mg/m², iv over 2 h on day 1 of each 14 day cycle Oxaliplatin 85 mg/m² in 500 ml G5%, iv over 2h on day 1 of each 14 day cycle Leucovorin 200 mg/m² in 250 ml NaCl 0,9%, iv over 1 h on day 1 of each cycle 5-FU 2600 mg/m², iv over 24 h on day 1 of each 14 day cycle
post-operative treatment trastuzumab mono therapy
Trastuzumab mono therapy for 9 cycles: Trastuzumab 6 mg/kg BW, iv over 1 h on day 1 of each 21 day cycle

Primary Outcomes

Measure
Rate of complete pathological responses (percentage of patients with pCR referring to the total number of enrolled and eligible patients), as evaluated centrally by a reference pathologist.
time frame: From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.

Secondary Outcomes

Measure
R0 resection rate
time frame: From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.
Relapse-free survival
time frame: From enrollment to end of follow up assessed up to 58 months
Overall survival
time frame: From enrollment to end of follow up assessed up to 58 months.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed adenocarcinoma of the gastroesophageal junction (AEG I-III) or the stomach (uT2, uT3, uT4, any N category, M0), or any T N+ M0 patient, with the following specifications: Endosonography and an esophageal-gastro-duodenoscopy; Categorization of gastroesophageal junction tumors according to the classification by Siewert (1987, cf. appendix 2) - Detection of an adenocarcinoma with HER2 3+ (IHC) or HER2 2+ (IHC) with amplification proven by FISH, SISH or CISH by an accredited local pathologist (for quality assurance tumor samples have to be available for a subsequent central review) - No preceding cytotoxic or targeted therapy - Male and female patients aged ≥ 18 years. If able to reproduce, patients must be willing to use highly effective methods of contraception during treatment and for 6 months after the end of treatment (adequate: methods fulfilling the requirements of the Note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals [CPMP/ICH/286/95 mod]). Female patients with reproductive ability must have performed a negative pregnancy test within 7 days of study entry. - ECOG ≤ 2 - Exclusion of distant metastasis by CT of thorax and abdomen, bone scan or MRI (if osseous lesions are suspected due to clinical signs) - Laparoscopic exclusion of peritoneal carcinomatosis, if suspected clinically - Adequate haematological, hepatic and renal function parameters: Leukocytes ≥ 3000/mm³, platelets ≥ 100,000/mm3; Serum creatinine ≤ 1.5 x upper limit of normal, or GFR > 40 ml/min; Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.5 x upper limit of normal, alkaline phosphatase ≤ 6 x upper limit of normal - Normal cardiac ejection fraction, as assessed by echocardiography - Written patient consent form Exclusion Criteria: - Known hypersensitivity against trastuzumab, murine proteins, 5-FU, leucovorin, oxaliplatin or docetaxel - Other known contraindications against trastuzumab, 5-FU, leucovorin, oxaliplatin, or docetaxel - Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV - Clinically significant valvular defect - Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix - Known brain metastases - Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy - Other severe internal disease or acute infection - Peripheral polyneuropathy > NCI Grade II - Chronic inflammatory bowel disease - On-treatment participation in another clinical study in the period 30 days prior to inclusion and during the study - Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment - Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4) - Any other concurrent antineoplastic treatment including irradiation

Additional Information

Official title Multicenter, Explorative Phase II Study of Perioperative 5-FU, Leucovorin, Docetaxel, and Oxaliplatin (FLOT) in Combination With Trastuzumab in Patients With HER2-positive, Locally Advanced, Resectable Adenocarcinoma of the Gastroesophageal Junction or Stomach (HerFLOT)
Principal investigator Ralf D Hofheinz, Prof. Dr.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by AIO-Studien-gGmbH.