AVELUMAB and CETUXIMAB and mFOLFOXIRI as Initial Therapy for Unresectable Metastatic Colorectal Cancer Patients

NCT04513951 | Completed Phase 2 DMC

• 1 other identifier: 2019-001501-24
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the efficacy of mFOLFOXIRI plus cetuximab and avelumab as first line treatment of patients with initially unresectable and previously untreated RAS wild-type metastatic colorectal cancer (mCRC), in terms of Progression-free Survival.

Conditions

Metastatic Colorectal Cancer

Keywords

modified FOLFOXIRI; Cetuximab; Avelumab

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival is defined as the time from enrollment to the first documentation of objective disease progression or death due to any cause, whichever occurs first.

  19 months

Secondary Outcomes (7)

• Toxicity Rate

  24 months

• Objective Response Rate

  19 months

• Immuno-related Objective Response Rate

  19 months

• Early Objective Response Rate

  up to 2 months from randomization

• Deepness of Response

  19 months

Study Arms (1)

mFOLFOXIRI + Cetuximab + Avelumab

EXPERIMENTAL

* Avelumab, 800 mg intravenous \[IV\] dose over 60 minutes, day 1, followed by * Cetuximab, 500 mg/m2 IV dose over 2 hours at cycle 1 (if well tolerated, it is administered over 90 minutes at cycle 2 and over 60 minutes by cycle 3), day 1, followed by * Irinotecan 150 mg/ m2 IV dose over 60 minutes day 1, followed by * Oxaliplatin 85 mg/m2 IV dose over 2 hours, day 1 in two-way with * L-Leucovorin 200 mg/ m2 IV dose over 2 hours, day 1 followed by * 5-fluoruracil 2400 mg/m2 IV dose 48 h-continuous infusion, starting on day 1; to be repeated every 14 days for a maximum of 12 cycles. If no progression occurs during the induction treatment, patients will receive maintenance with 5-FU/LV plus cetuximab and avelumab at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus cetuximab and avelumab will be repeated biweekly until disease progression, unacceptable toxicity, patient's refusal or consent withdrawal.

Drug: 5Fluorouracil; Drug: L-leucovorin; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Cetuximab; Drug: Avelumab

Interventions

5Fluorouracil DRUG

phase II

mFOLFOXIRI + Cetuximab + Avelumab

L-leucovorin DRUG

phase II

mFOLFOXIRI + Cetuximab + Avelumab

Irinotecan DRUG

phase II

mFOLFOXIRI + Cetuximab + Avelumab

Oxaliplatin DRUG

phase II

mFOLFOXIRI + Cetuximab + Avelumab

Cetuximab DRUG

phase II

mFOLFOXIRI + Cetuximab + Avelumab

Avelumab DRUG

phase II

mFOLFOXIRI + Cetuximab + Avelumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of colorectal adenocarcinoma;
• Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
• At least one measurable lesion according to RECIST 1.1.;
• Availability of a tumour tissue sample (primary tumour and/or metastatic sites);
• Male or female of 18-75 years of age;
• ECOG PS ≤2 for patients aged ≤70 years; ECOG PS 0 for patients aged 71 to 75 years;
• Life expectancy of at least 12 weeks;
• Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse;
• RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) wild-type status of primary colorectal cancer or related metastasis (local or central laboratory assessment);
• Adequate haematological function: neutrophils \>1.5 x 109/L, platelets \>100 x 109/L, haemoglobin \>9 g/dl;
• Adequate liver and renal function: total bilirubin 1.5 time the upper-normal limits (UNL) of the normal values and AST (SGOT) and/or ALT (SGPT) \<2.5 x UNL (or \<5 x UNL in case of liver metastases) alkaline phosphatase \<2.5 x UNL (or \<5 x UNL in case of liver metastases); creatinine clearance ≥50 mL/min or serum creatinine 1.5 x UNL;
• INR or aPTT ≤1.5 × ULN. Patients who are on therapeutic doses of anti-coagulants are eligible if they are on a stable dose of anti-coagulant for 28 days with stable INR and PTT values;
• Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 continuous months, are surgically sterile, or are sexually inactive;
• Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriere contraceptive measure or oral contraception);
• Will and ability to comply with the protocol;

You may not qualify if:

• Radiotherapy to any site within 4 weeks before the study;
• Previous adjuvant oxaliplatin-containing chemotherapy;
• Previous treatment with cetuximab;
• Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents;
• Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer);
• Major surgery for any reason, except diagnostic biopsy, within 4 weeks of the trial treatment and/or if the subject has not fully recovered from the surgery within 4 weeks of the trial treatment, or anticipation of the need for major surgical procedure during the course of the study;
• Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to \< 10 mg prednisone daily).
• Notes:
• Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before first dose of trial treatment;
• Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone.
• All subjects with brain metastases, except those meeting the following criteria:
• a. Brain metastases have been treated locally, have not been progressing at least 2 months after completion of therapy, and no steroid maintenance therapy is required, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable).
• Symptomatic peripheral neuropathy \> 2 grade NCI-CTCAE v5.0;
• Other co-existing malignancies or previous malignant disease (other than colorectal cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, breast);
• Prior organ transplantation, including allogeneic stem cell transplantation;

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (1)

U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - University of Pisa

Pisa, 56126, Italy

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Irinotecan; Oxaliplatin; Cetuximab; avelumab

Condition Hierarchy (Ancestors)

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)

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; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

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

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 14, 2020
• Study Start: April 1, 2020
• Primary Completion: June 28, 2023
• Study Completion: December 31, 2024
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)