GastroEsophageal Cancer
Conditions
Brief summary
This is an open-label,multi-centre, phase 1b safety and feasibility study aiming to assess the safey and feasibility of bemarituzumab plus chemiotherapy (FLOT) for the peri-operative treatment of resectable gastroesophageal cancer. Following this neo-adjuvant part, patients should undergo surgery. Following surgery, patients will receive FLOT chemotherapy in combination with bemarituzumab. Imaging will be performed every 3 months for the first 2 years and thereafter every 6 months as per standard of care.
Interventions
DRUGBemarituzumab
• Bemarituzumab will be given as a IV infusion
DRUGFLOT
FLOT will be given as a IV infusion
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed screening informed consent * Age ≥ 18 years * Availability of a diagnostic tumour sample for central evaluation (FFPE block or minimum 10 slides). * Histologically proven, previously untreated, locally advanced, resectable gastric/GEJ adenocarcinoma cT2-cT4, N0, M0 or cTany, N+, M0. Note: if the results of the staging laparoscopy are pending at this stage it is acceptable to include the patients in this step, in the interest of patient time-to-treatment. * Planned peri-operative treatment with FLOT chemotherapy and surgically assessed feasible R0 resection * Centrally confirmed FGFR2b overexpression as defined by ≥10% tumour cells with 2+/3+ FGFR2b staining by immunohistochemistry (IHC) * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Previously untreated, locally advanced, histologically confirmed, resectable gastric/GEJ adenocarcinoma cT2-cT4, N0, M0 or cTany, N+, M0 by radiological and surgical staging * Adequate hematologic and organ function
Exclusion criteria
* Prior anticancer treatment for the disease under investigation * History or evidence of systemic disease or ophthalmological disorders requiring chronic use of ophthalmologic corticosteroids * Evidence of any ongoing ophthalmologic abnormalities or symptoms that are recent (within 4weeks) or actively progressing * Unwillingness to avoid the use of contact lenses during study treatment and follow-up period of at least 100 days after end of treatment. * Evidence of, or recent (within 6 months) history of, corneal defects, corneal ulcerations, keratitis, or keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer. Recent (within 6 months) corneal surgery or ophthalmologic laser treatment * History of solid organ transplantation * History of interstitial lung disease * Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study * Patients on immunosuppressive therapy or having immune system disorders, including auto-immune diseases. Concurrent steroid use of not more than an equivalent of 10 mg/day prednisolone is allowed. Inhaled, intranasal, intraocular, and/or joint injections of corticosteroids are allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion rate of neoadjuvant treatment followed by surgery without serious anastomotic leakage, defined as the percentage of patients who completed the treatment without grade 2 or more anastomotic leakage as per Clavien-Dindo Classification | 2.3 years from first patient in | Patients will be considered to have successfully completed the neo-adjuvant treatment if they complete the 4 cycles of FLOT plus Bemarituzumab. Additionally, anastomotic leakage will be reported as post-surgery complication following the modified Clavien-Dindo Classification |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response | 3.6 years from first patients in | — |
| Progression free survival (PFS) | 3.6 years from first patients in | Progression-free survival is defined as the time interval from enrolment to the first event of progression/recurrence |
| Overall survival (OS) | 3.6 years from first patients in | Overall survival will be computed from the date of enrolment to the date of death |
| Treatment-emergent adverse events | 3.6 years from first patients in | — |
| Major pathological response | 3.6 years from first patients in | Major pathological response rate will be computed as the percentage of patients who had major tumour regression (\< 10% vital residual tumour cells) after neoadjuvant treatment. |
| Completion rate of neoadjuvant and adjuvant therapy | 3.6 years from first patients in | — |
| Postoperative complications according to CLAVIEN DINDO classification | 3.6 years from first patients in | — |
| 30 and 90 day-mortality after surgery | 1.7 years from first patients in | — |
| R0 resection | 3.6 years from first patients in | — |
Contacts
Primary ContactEORTC EORTC
Outcome results
None listed