MoLiMoR - A Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab

NCT04554836 | Completed Phase 2 Results DMC

• 1 other identifier: 4213000
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, prospective, randomized, multicenter phase II trial that will evaluate the efficacy and safety of intermittent addition of cetuximab to a FOLFIRI-based first line therapy to patients with RAS (Rat sarcoma)-mutant mCRC (Metastatic colorectal cancer) diagnosis who convert to RAS wild-type using monitoring of the RAS mutation status by liquid biopsy.

Conditions

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum

Keywords

Left sided Adenocarcinoma of the Colon; RAS mutated

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Evaluation of efficacy in terms of progression free survival (PFS)

  From date of randomization up to 24 months

Secondary Outcomes (9)

• Overall Survival (OS)

  From date of randomization up to 24 months.

• Time to Failure of Treatment Strategy (TFTS)

  After randomization up to 24 months.

• PFS (Progression Free Survival) Rate

  1 year after date of randomization

• Depth of Response

  From the start of the first line treatment in the study up to 24 months.

• Metastasis Resections.

  From the start of the first line treatment in the study up to 24 months.

Study Arms (2)

FOLFIRI + cetuximab

EXPERIMENTAL

Patients in Arm A will receive FOLFIRI + cetuximab until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first. The recurrence of RAS-mutation without PD to switch back to FOLFIRI. In case of repeated conversion to RAS wild-type without PD, treatment will shift to FOLFIRI + cetuximab again, and so on. Switches of treatment will proceed until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first. \[FOLFIRI = Irinotecan, Folinic acid (racemic), Fluorouracil (5-FU)\]

Drug: Cetuximab; Other: FOLFIRI

FOLFIRI

OTHER

Patients in Arm B will continue therapy with FOLFIRI until PD, unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first.

Other: FOLFIRI

Interventions

Cetuximab DRUG

Patients in Arm A will receive FOLFIRI +cetuximab.

FOLFIRI + cetuximab

FOLFIRI OTHER

Irinotecan, Folinic acid (racemic), Fluorouracil (5-FU)

FOLFIRI; FOLFIRI + cetuximab

Eligibility Criteria

• Age: 18 Years - 99 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 left-sided colon or rectum with metastases (metastatic colorectal cancer), primarily non-resectable, confirmed RAS mutations proven in the primary tumor or metastasis (KRAS ans NRAS exon 2, 3, 4)
• Age ≥ 18 years on day of signing informed consent
• No previous chemotherapy for metastatic disease (1- 2 cycles FOLFIRI or mFOLFIRI are permitted before enrolment until RAS status is determined)
• Patients suitable for chemotherapy administration
• ECOG (Eastern Cooperative Oncology Group) status 0-1
• Consent to liquid biopsy and mutation analysis
• Estimated life expectancy \> 3 months
• Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria (chest CT and abdominal CT 4 weeks or less before enrollment)
• Adequate bone marrow function defined as: Leukocytes 3.0 x 10 9/L with neutrophils 1.5 x 10 9/L, Thrombocytes 100 x 10 9/L, Hemoglobin 9 g/dL
• Adequate hepatic function defined as: Serum bilirubin 1.5 x ULN (Upper limit of normal), ALAT (Alanine-aminotransferase (= SGPT = serum glutamate pyruvate transaminase) and ASAT (aspartate-aminotransferase (= SGOT = serum glutamate oxalacetate transaminase) 2.5 x ULN (Upper limit of normal) (in the presence of hepatic metastases, ALAT and ASAT 5 x ULN)
• Adequate renal function: Creatinine clearance ≥ 50 mL/min
• Adequate cardiac function defined as Normal ECG and echocardiogram with a left ventricular ejection fraction (LVEF) of 55%
• INR (International normalized ratio) \< 1.5 and aPTT (activated Partial thromboplastin time) \< 1.5 x ULN (patients without anticoagulation). Therapeutic anticoagulation is allowed if INR and aPTT have remained stable within the therapeutic range for at least 2 weeks.
• Time interval of at least 6 months since last administration of any previous neoadjuvant/adjuvant chemotherapy or radiochemotherapy of the primary tumor in curative treatment intention to start of 1st line treatment
• Any relevant toxicities of prior treatments must have resolved to grade ≤ 1 according to the CTCAE (version 5), except alopecia

You may not qualify if:

• Right sided mCRC
• Primarily resectable metastases
• Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study (1- 2 cycles FOLFIRI or mFOLFIRI are permitted before enrolment)
• Patients with known brain metastases
• Symptomatic peritoneal carcinosis
• Progressive disease before randomization
• History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune colitis or chronic diarrhea
• Grade II heart failure (NYHA classification), Myocardial infarction, balloon angioplasty (PTCA) with or without stenting, and cerebral vascular accident/stroke within the past 12 months before enrollment, unstable angina pectoris, serious cardiac arrhythmia according to investigator's judgment requiring medication
• Active infection with hepatitis B or C
• Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
• Additional cancer; Exceptions include adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy without evidence of recurrence
• Uncontrolled hypertension
• Marked proteinuria (nephrotic syndrome)
• Arterial thromboembolism or severe hemorrhage within 6 months prior to randomization (with the exception of tumor bleeding before tumor resection surgery)
• Hemorrhagic diathesis or tendency towards thrombosis

Sponsors & Collaborators

• TheraOp: lead

Study Sites (4)

Universitätsklinikum Knappschaftskrankenhaus

Bochum, Germany

Location

Onkologisches Zentrum (Dachau II)

Dachau, Germany

Location

Kliniken-Essen-Mitte Evang. Huyssens-Stiftung

Essen, Germany

Location

Evangelisches Krankenhaus Hamm

Hamm, Germany

Location

Related Publications (1)

• Klein-Scory S, Wahner I, Maslova M, Al-Sewaidi Y, Pohl M, Mika T, Ladigan S, Schroers R, Baraniskin A. Evolution of RAS Mutational Status in Liquid Biopsies During First-Line Chemotherapy for Metastatic Colorectal Cancer. Front Oncol. 2020 Jul 16;10:1115. doi: 10.3389/fonc.2020.01115. eCollection 2020.

  PMID: 32766143 RESULT

Related Links

• Evolution of RAS Mutational Status in Liquid Biopsies During First-Line Chemotherapy for Metastatic Colorectal Cancer.

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Cetuximab; IFL protocol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Prof. Dr. Alexander Baraniskin
• Organization: Evangelisches Krankenhaus Hamm Werler Str. 110, 59063 Hamm

Alexander.Baraniskin@ruhr-uni-bochum.de

+49 (0) 2381 / 589 1863

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 18, 2020
• Study Start: December 29, 2020
• Primary Completion: June 11, 2024
• Study Completion: June 11, 2024
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)