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

June 16, 2017 updated by: AIO-Studien-gGmbH

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.
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)
From enrollment to end of follow up assessed up to 58 months
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.
From enrollment to end of follow up assessed up to 58 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AIO-Studien-gGmbH

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2011

Primary Completion (Actual)

August 25, 2014

Study Completion (Actual)

September 12, 2016

Study Registration Dates

First Submitted

October 24, 2011

First Submitted That Met QC Criteria

November 11, 2011

First Posted (Estimate)

November 16, 2011

Study Record Updates

Last Update Posted (Actual)

June 19, 2017

Last Update Submitted That Met QC Criteria

June 16, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIO-STO-0310
  • 2011-001507-13 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Adenocarcinoma of the Gastroesophageal Junction

Clinical Trials on 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe