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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01472029
First Posted: November 16, 2011
Last Update Posted: June 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
AIO-Studien-gGmbH
  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: Intervention Model: Single Group Assignment
Masking: None (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:


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. ]

    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. ]
    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 ]
    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. ]
    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.


Enrollment: 53
Study Start Date: December 2011
Study Completion Date: September 12, 2016
Primary Completion Date: August 25, 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01472029


Locations
Germany
Tagestherapiezentrum am ITM & III. Medizinische Klinik Universitätsmedizin Mannheim
Mannheim, Germany, D-68167
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

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT01472029     History of Changes
Other Study ID Numbers: AIO-STO-0310
2011-001507-13 ( EudraCT Number )
First Submitted: October 24, 2011
First Posted: November 16, 2011
Last Update Posted: June 19, 2017
Last Verified: June 2017

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

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Docetaxel
Oxaliplatin
Trastuzumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action