Clinical trial NCT01472029: Explorative Phase II Study of Perioperative Treatment in Patients With Adenocarcinoma of the Gastroesophageal Junction or Stomach
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Gastroesophageal Junction
Adenocarcinoma of the Stomach
Keywords: Adenocarcinoma
Gastroesophageal junction
Stomach
HER2
Lead sponsor: AIO-Studien-gGmbH
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2011-11-16
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.
* 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

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.
timeFrame: From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.
Secondary outcomes:
measure: R0 resection rate
timeFrame: From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.
measure: Relapse-free survival
timeFrame: From enrollment to end of follow up assessed up to 58 months
measure: Overall survival
timeFrame: From enrollment to end of follow up assessed up to 58 months.
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Tagestherapiezentrum am ITM & III. Medizinische Klinik Universitätsmedizin Mannheim
Study officials:
affiliation: Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim
name: Ralf D Hofheinz, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hofheinz RD, Hegewisch-Becker S, Kunzmann V, Thuss-Patience P, Fuchs M, Homann N, Graeven U, Schulte N, Merx K, Pohl M, Held S, Keller R, Tannapfel A, Al-Batran SE. Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group. Int J Cancer. 2021 Sep 15;149(6):1322-1331. doi: 10.1002/ijc.33696. Epub 2021 May 29.