Adenocarcinoma of the Gastroesophageal JunctionPhase 2HerFLOTNCT01472029
Explorative Phase II Study of Perioperative Treatment in Patients With Adenocarcinoma of the Gastroesophageal Junction or Stomach
A Phase 2 study testing 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab and Post-operative treatment trastuzumab mono therapy in people with Adenocarcinoma of the Gastroesophageal Junction and Adenocarcinoma of the Stomach, run by AIO-Studien-gGmbH at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Gastroesophageal Junction, Adenocarcinoma of the Stomach
- What is being tested?
- 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab and Post-operative treatment trastuzumab mono therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2011to 12 Sep 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Tagestherapiezentrum am ITM & III. Medizinische Klinik Universitätsmedizin Mannheim
Mannheim, D-68167
About this study
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)
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.
- Being tested
- 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab, Post-operative treatment trastuzumab mono therapy
- Keywords
- Adenocarcinoma, Gastroesophageal junction, Stomach, HER2
- Medical subject headings
- Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumabDrug
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 therapyDrug
Trastuzumab mono therapy for 9 cycles:
Trastuzumab 6 mg/kg BW, iv over 1 h on day 1 of each 21 day cycle
| Study group | Role | What they receive |
|---|---|---|
| 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab | Experimental | Not described Receives: Drug: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab; Drug: Post-operative treatment trastuzumab mono therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.
Secondary outcomes (3)
R0 resection rate
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.
Measured: From enrollment to surgery after pre-operative treatment (4 cycles = 8 weeks) for 9 weeks.
Relapse-free survival
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)
Measured: From enrollment to end of follow up assessed up to 58 months
Overall survival
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.
Measured: From enrollment to end of follow up assessed up to 58 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2011 (estimated)
- Study startDec 2011
- Primary completion25 Aug 2014
- Study completion12 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adenocarcinoma of the Gastroesophageal JunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- AIO-Studien-gGmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Ralf D Hofheinz, Prof. Dr., Principal investigator, Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01472029
- Sponsor's protocol ID
- AIO-STO-0310
- Other IDs
- 2011-001507-13
- Acronym
- HerFLOT
- Status last verified
- Jun 2017
- First submitted
- 24 Oct 2011
- Last updated
- 19 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34019698
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01472029
- Acronym / sponsor ID
- HerFLOT / AIO-STO-0310
- Keywords
- Adenocarcinoma, Gastroesophageal junction, Stomach, HER2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- AIO-Studien-gGmbHUniversity, hospital or other
- Collaborators
- Roche Pharma AG
- Study start
- Dec 2011
- Primary completion
- 25 Aug 2014 (actual)
- Study completion
- 12 Sep 2016 (actual)
- First posted
- 16 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab | Experimental | Drug: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab, Drug: Post-operative treatment trastuzumab mono therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumabPre-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 | 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab |
| Post-operative treatment trastuzumab mono therapyTrastuzumab mono therapy for 9 cycles: Trastuzumab 6 mg/kg BW, iv over 1 h on day 1 of each 21 day cycle | Drug | 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab |
Primary outcome
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.
3 secondary outcomes
R0 resection rate
Time frame: 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
Overall survival
Time frame: From enrollment to end of follow up assessed up to 58 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2017.
- Derived from this study: PubMed 34019698Hofheinz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ralf D Hofheinz, Prof. Dr. principal investigator
Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT), trastuzumab and Post-operative treatment trastuzumab mono therapy in people with Adenocarcinoma of the Gastroesophageal Junction and Adenocarcinoma of the Stomach, run by AIO-Studien-gGmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01472029, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2017.