Text Size

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

This study is currently recruiting participants.
Verified August 2012 by AIO-Studien-gGmbH
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
AIO-Studien-gGmbH
ClinicalTrials.gov Identifier:
NCT01472029
First received: October 24, 2011
Last updated: August 16, 2012
Last verified: August 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Adenocarcinoma of the Stomach
 Drug: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab
Drug: Post-operative treatment trastuzumab mono therapy
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AIO-Studien-gGmbH:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • R0 resection rate [ Time Frame: From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks. ] [ Designated as safety issue: No ]
    The R0 rate is defined as the number of patients with negative surgical margins and no tumor left macroscopically, divided by the total number of recruited eligible patients.

  • Relapse-free survival [ Time Frame: From enrollment to end of follow up assessed up to 58 months ] [ Designated as safety issue: Yes ]
    Relapse-free survival (RFS) will be defined as the time from enrolment to the time of disease progression or relapse or death, or to the date of last tumor assessment without any such event (censored observation)

  • Overall survival [ Time Frame: From enrollment to end of follow up assessed up to 58 months. ] [ Designated as safety issue: Yes ]
    The duration of overall survival (OS) will be determined by measuring the time interval from enrolment to the date of death or last observation, including survival rates after 1, 2 and 3 years.


Estimated Enrollment: 53
Study Start Date: December 2011
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab Drug: 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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01472029

Contacts
Contact: Ralph Keller +49033229329 ext 34 keller@krebsgesellschaft.de
Contact: Katrin Krause +49033229329 ext 32 krause@krebsgesellschaft.de

Locations
Germany
Tagestherapiezentrum am ITM & III. Medizinische Klinik Universitätsmedizin Mannheim Recruiting
Mannheim, Germany, D-68167
Contact: Ralf D Hofheinz, Prof. Dr.     +49 621-383-2855     ralf.hofheinz@umm.de    
Principal Investigator: Ralf D Hofheinz, Prof. Dr.            
Sponsors and Collaborators
AIO-Studien-gGmbH
Roche Pharma AG
Investigators
Principal Investigator: Ralf D Hofheinz, Prof. Dr. Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim
  More Information

No publications provided

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT01472029     History of Changes
Other Study ID Numbers: AIO-STO-0310, 2011-001507-13
Study First Received: October 24, 2011
Last Updated: August 16, 2012
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by AIO-Studien-gGmbH:
Adenocarcinoma
Gastroesophageal junction
Stomach
HER2

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Mucinous
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
 Oxaliplatin
Docetaxel
Trastuzumab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex

ClinicalTrials.gov processed this record on May 23, 2013