Explorative Phase II Study of Perioperative Treatment in Patients With Adenocarcinoma of the Gastroesophageal Junction or Stomach

NCT ID: NCT01472029

Last Updated: 2017-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2016-09-12

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.

Conditions

Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach

Study Design

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

Study Groups

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Trastuzumab mono therapy for 9 cycles:

Trastuzumab 6 mg/kg BW, iv over 1 h on day 1 of each 21 day cycle

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

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

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

AIO-Studien-gGmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralf D Hofheinz, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim

Locations

Tagestherapiezentrum am ITM & III. Medizinische Klinik Universitätsmedizin Mannheim

Mannheim, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 34019698 (View on PubMed)

Other Identifiers

2011-001507-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AIO-STO-0310

Identifier Type: -

Identifier Source: org_study_id