Avelumab added to FOLFIRI plus cetuximab followed by avelumab maintenance in patients with previously untreated RAS/BRAF wild-type metastatic colorectal cancer - the phase II FIRE-6-avelumab study MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Bavencio
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
CAS Number: 1537032-82-8
Current Sponsor code: Avelumab
Concentration unit: mg/ml milligra
Sponsors
Klinikum der Ludwig-Maximilians-Universität München - Klinikum Großhadern (vertreten durch den kaufmännischen Direktor)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed, UICC stage IV adenocarcinoma of the colon or rectum with metastases (mCRC), metastases primarily non resectable or surgery refused by the patient 2. RAS wild-type tumour status (KRAS and NRAS, exon 2, 3, 4) and BRAF wild-type tumour status (V600, exon 15) (proven in the primary tumour or metastasis) 3. Adult patients = 18 years 4. ECOG performance status 0-1 5. Patients suitable for chemotherapy administration 6. Patient's written declaration of consent obtained 7. Estimated life expectancy > 3 months 8. Presence of at least one measurable reference lesion according to the RECIST v1.1 criteria 9. Tumour tissue available for molecular and genetic profiling regarding BRAF/RAS mutation status and MSI Status 10. Females of childbearing potential (FCBPs) must agree to use highly effective contraceptive measures (Pearl index =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Proof of a RAS mutation (KRAS or NRAS, exons 2, 3, 4) or BRAF mutation (V600 in exon 15) in the tumour (proven in primary tumour or metastasis) or absence of testing for RAS or BRAF mutations 2. Primarily resect metastases and the patient wishes for resection 3. = Grade II heart failure (NYHA classif) 4. Myocardial infarct, balloon angioplasty (PTCA) with or without stenting + cerebral vascular accident/stroke within the past 12 months before start of study treatm, unstable angina pectoris, serious cardiac arrhythmia according to investigator’s judgem. requiring medic. 5. Pre-existing pulmonary fibrosis or immune pneumonitis 6. Active autoimmune disease that might be negatively affected by an immune checkpoint inhibitor. Patients diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosup. treatment are eligible. 7. Prior organ transpl., incl allogeneic stem cell transpl. 8. Current use of immunosuppressive medi, except for the following: a) Intranasal, inhaled, topical steroids, or local steroid inject (e.g., intra-articular inject); b) System corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c) Steroids as premedic. for hypersens reactions (e.g., CT scan premedi). 9. Pregnancy (absence of pregnancy to be ascertained by a negative ß-HCG test) or breast feeding 10. Medi or psychol impairments assoc. with restricted ability to give consent or not allowing conduct of the study 11. Add cancer treatm (chemoth., radiation, immunoth or hormone treatm.) during the study treatm in first-line (treatm that are conducted as part of an anthroposophic or homeopathic treatm approach, e.g. mistletoe therapy do not represent an excl.cr.) 12. Previous chemoth. for the Color. cancer with the exception of adjuvant treatm., compl at least 6 months bef. entering the study 13. Adv. drug reaction > NCI CTCAE Grade1 that has not yet resolved, attributed to a previous treatm or measure for treatm of the CRC. However, alopecia (all grades) and oxaliplatin-induced neurotox = grade 2 are acceptable. 14. Participat in a clinic study or experim. drug treatm within 30 days prior to study incl. or within a period of 5 half-lives of the substances admin. in a clinical study or during an experimental drug treatm prior to incl. in the study, depending on which period is longest or simultaneous participation in another study while taking part in the study 15. Known hypersensitivity or allergic react to any of the following substances: folinic acid, 5-FU, irinotecan, cetuximab, avelumab and chemically related substances and/or hypersens to any of the components in the formulations of the aforementioned subst, incl known hypersensitivity reactions to monoclonal antibodies NCI CTCAE Grade = 3. 16. Known hypersensitivity to Chinese hamster ovary cell (CHO) – cellular products or other recombinant human or humanised monocl antibodies 17. Patients with known brain metastases. In case of clinical suspicion of brain metastasis a cranial MRI or CT must be performed to rule out brain metastasis bef. study inclus. 18. History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune colitis or chronic diarrhoea 19. Symptomatic peritoneal carcinosis 20. Severe, non-healing wounds, ulcers or bone fractures 21. Patients with act. infect requiring syst. therapy 22. Known history of testing positive for HIV or known acquired immunodeficiency syndr. 23. Active or chronic Hepatitis B virus (HBV) or hepa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the efficacy of FOLFIRI plus cetuximab in combination with avelumab followed by avelumab maintenance therapy in patients with previously untreated RAS/BRAF wild-type mCRC.;Secondary Objective: • To assess the efficacy and safety profile of the tested treatment strategy • To assess the feasibility of the tested treatment strategy;Primary end point(s): • Progression-free survival (PFS) according to RECIST v1.1;Timepoint(s) of evaluation of this end point: Restaging according to RECIST 1.1 will be performed every eight weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective response rate (ORR) according to RECIST v1.1 and irRECIST • Progression-free survival (PFS) according to irRECIST • Progression-free survival rate after 12 months of treatment (PFSR@12) according to RECIST v1.1 and irRECIST • Overall survival (OS) • Duration of treatment • Type, frequency and severity of adverse events (severity according to NCI CTCAE version 5.0);Timepoint(s) of evaluation of this end point: • Restaging according to RECIST 1.1 will be performed every eight weeks • OS will be evaluated in a continously manner, after study Treatment every 3 month until death or end of study • Evaluated when end of treatment is reached • Safety and tolerability will be evaluated in a continously manner | — |
Countries
Germany
Contacts
Public ContactMatthias Wolff
Klinikum der Ludwig-Maximilians-Universität München - Klinikum Großhadern - Studiensekratariat
Outcome results
None listed