FOLFIRI + Cetuximab + Avelumab RAS Wild-type CRC

NCT05217069 | Completed Phase 2

• 1 other identifier: FIRE-6
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

Within the proposed single arm multicenter phase-II trial it is intended to investigate the feasi-bility of adding Avelumab to FOLFIRI plus Cetuximab after 4 cycles (2 months) of treatment with FOLFIRI plus Cetuximab. After 4 more cycles of FOLFIRI plus Cetuximab plus Avelumab the treatment will be de-escalated to Avelumab as a maintenance concept until progression of the disease according to RECIST 1.1 has occurred.

Conditions

Treatment Related Cancer

Keywords

CRC; Avelumab; FIRE; RAS

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The primary clinical objective is to determine the efficacy of a standard 1st-line regimen (FOLFIRI plus cetuximab) in patients with RAS wild-type mCRC with Avelumab mainte-nance in terms of progression free survival rate after 8 months (according to RECIST 1.1).

  up to 8 months

Secondary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  up to 36 months

• Efficacy of experimental Regimen according to response rate

  up to 36 months

• Efficacy of experimental Regimen according to Overall survial

  up to 36 months

Study Arms (1)

RAS wild-type Avelumab

OTHER

Induction therapy: FOLFIRI 5-FU: 400 mg/m2 (i.v. bolus) Folinic acid: 400mg/m2 Irinotecan: 180 mg/m2 5-FU: 2.400 mg/m2 (i.v. 46h) Cetuximab 400 mg/m2 i.v. 120min initial dose 250 mg/m2 i.v. 60min q 1w Maintenance therapy: Avelumab 10mg/kg IV (day 1 q2w)

Drug: 5-FU; Drug: Folinic Acid; Drug: Irinotecan; Drug: Cetuximab; Drug: Avelumab

Interventions

5-FU DRUG

400 mg/m2 (i.v. bolus) 2400 mg/m2 (i.v. 46h)

RAS wild-type Avelumab

Folinic Acid DRUG

400mg/m2

RAS wild-type Avelumab

Irinotecan DRUG

180 mg/m2

RAS wild-type Avelumab

Cetuximab DRUG

400 mg/m2 i.v. 120min initial dose 250 mg/m2 i.v. 60min q 1w

RAS wild-type Avelumab

Avelumab DRUG

10mg/kg IV (day 1 q2w)

RAS wild-type Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, UICC stage IV adenocarcinoma of the colon or rectum with metastases (metastatic colorectal cancer), metastases primarily non-resectable or surgery refused by the patient
• RAS wild-type tumour status (KRAS and NRAS exon 2, 3, 4) (proven in the primary tumour or metastasis)
• Age ≥18
• ECOG performance status 0-1
• Patients suitable for chemotherapy administration
• Patient's written declaration of consent obtained
• Estimated life expectancy \> 3 months
• Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria
• Primary tumour tissue available and patient consents to storage and molecular and genetic profiling of tumour material. Molecular profiling of blood samples is optionally performed.
• Females of childbearing potential (FCBPs) and men must agree to use highly effec-tive contraceptive measures (Pearl index \<1) or practice true abstinence from any heterosexual intercourse (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject) for the duration of the study treatment and for at least 6 months after last administration of study medication. A woman will be considered as being of childbearing potential unless she is at least 50 years old and moreover has gone through menopause for at least 2 years or has been surgically sterilised.
• Adequate bone marrow function:
• Leukocytes ≥ 3.0 x 109/L with neutrophils ≥ 1.5 x 109/L
• Thrombocytes ≥ 100 x 109/L
• Haemoglobin ≥ 5.6 mmol/L (equivalent to 9 g/dL)
• Adequate hepatic function:

You may not qualify if:

• Proof of a RAS mutation (KRAS or NRAS, exons 2, 3, 4 in the tumor (proven in the primary tumor or metastasis) or absence of testing for RAS mutation
• Primarily resectable metastases and the patient wishes for resection
• ≥ Grade II heart failure (NYHA classification)
• Myocardial infarction, balloon angioplasty (PTCA) with or without stenting, and cere-bral vascular accident/stroke within the past 12 months before start of study treat-ment, unstable angina pectoris, serious cardiac arrhythmia according to investigator's judgement requiring medication.
• Pre-existing pulmonary fibrosis or immune pneumonitis
• Active autoimmune disease that might be negatively affected by an immune check-point inhibitor. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Prior organ transplantation, including allogeneic stem cell transplantation
• Current use of immunosuppressive medication, except for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan pre-medication).
• Pregnancy (absence of pregnancy to be ascertained by a negative beta hCG test) or breast feeding
• Medical or psychological impairments associated with restricted ability to give con-sent or not allowing conduct of the study
• Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
• Toxicity \> Grade 1 that has not yet resolved, attributed to a previous treatment or measure for treatment of the mCRC. However, alopecia (all grades) and oxaliplatin-induced neurotoxicity ≤ Grade 2 are acceptable.

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• ClinAssess GmbH: collaborator

Study Sites (1)

Ludwig Maximilians University

Munich, 81377, Germany

Location

MeSH Terms

Conditions

Neoplasms, Second Primary

Interventions

Fluorouracil; Leucovorin; Irinotecan; Cetuximab; avelumab

Condition Hierarchy (Ancestors)

Neoplasms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dominik Modest, PD Dr.

  Ludwig-Maximilians - University of Munich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director CCC-Munich

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: February 1, 2022
• Study Start: September 27, 2019
• Primary Completion: September 1, 2023
• Study Completion: October 18, 2023
• Last Updated: April 16, 2025

Record last verified: 2025-04

Locations

DE (1)