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)

AIO-Studien-gGmbH1 site in 1 country53 target enrollmentDecember 2011

ConditionsAdenocarcinoma of the Gastroesophageal Junction Adenocarcinoma of the Stomach

Interventions5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab Post-operative treatment trastuzumab mono therapy

Drugs5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab Post-operative treatment trastuzumab mono therapy

Overview

Phase: Phase 2
Intervention: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab
Conditions: Adenocarcinoma of the Gastroesophageal Junction
Sponsor: AIO-Studien-gGmbH
Enrollment: 53
Locations: 1
Primary Endpoint: 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.
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

December 2011

End Date

September 12, 2016

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

AIO-Studien-gGmbH

Responsible Party

Sponsor

Eligibility Criteria

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.
•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

Arms & Interventions

5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab

Intervention: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab

5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab

Intervention: Post-operative treatment trastuzumab mono therapy

Outcomes

Primary Outcomes

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.

The experimental therapy would be rated as insufficiently active, if the observed pCR rate is 10 % or lower, as this corresponds to the expectations after chemotherapy alone. The experimental therapy would be considered to be a promising candidate for further development (e.g. in a phase III trial), if the true pCR rate amounted to 20% or more.

Secondary Outcomes

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