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

NCT01472029 | Completed Phase 2 DMC

• 2 other identifiers: AIO-STO-03102011-001507-13
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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

Keywords

Adenocarcinoma; Gastroesophageal junction; Stomach; HER2

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.

Secondary Outcomes (3)

• R0 resection rate

  From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.

• Relapse-free survival

  From enrollment to end of follow up assessed up to 58 months

• Overall survival

  From enrollment to end of follow up assessed up to 58 months.

Study Arms (1)

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

EXPERIMENTAL

Drug: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab; Drug: Post-operative treatment trastuzumab mono therapy

Interventions

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

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

Post-operative treatment trastuzumab mono therapy DRUG

Trastuzumab mono therapy for 9 cycles: Trastuzumab 6 mg/kg BW, iv over 1 h on day 1 of each 21 day cycle

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Roche Pharma AG: collaborator

Study Sites (1)

Tagestherapiezentrum am ITM & III. Medizinische Klinik Universitätsmedizin Mannheim

Mannheim, D-68167, Germany

Location

Related Publications (1)

• 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.

  PMID: 34019698 DERIVED

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Fluorouracil; Leucovorin; Docetaxel; Oxaliplatin; Trastuzumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ralf D Hofheinz, Prof. Dr.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2011
• First Posted: November 16, 2011
• Study Start: December 1, 2011
• Primary Completion: August 25, 2014
• Study Completion: September 12, 2016
• Last Updated: June 19, 2017

Record last verified: 2017-06

Locations

DE (1)