Serum cytokine levels as predictors of the efficacy of aflibercept in combination with FOLFIRI in metastatic Colo-Rectal Cancer patients (mCRC)

Phase 1

• Conditions: Metastatic Colo-Rectal Cancer; MedDRA version: 21.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003509-16-IT
• Lead Sponsor: FONDAZIONE RICERCA TRASLAZIONALE (FORT)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-01-20
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 124

Inclusion Criteria

1. Adult age (>= 18 years old);
2. An Eastern Cooperative Oncology Group (ECOG);
performance status (PS) of 0 or 1;
3. Histologically or cytologically proven colorectal
adenocarcinoma with metastatic disease not menable to potentially curative treatment;
4. Measurable disease according to the RECIST criteria 1.1;
5. Documented progression while on or after completion of a single prior oxaliplatin-containing regimen in patients treated in the neoadjuvant and metastatic setting; documented relapsing disease within 6 months of completion of oxaliplatinbased regimen in patients treated in the adjuvant setting;
6. Aflibercept in combination with irinotecan planned as per standard clinical practice and decision by the treating oncologist;
7. Any adverse events from prior anticancer therapy must have recovered to grade = 1 ([NCI-CTCAE] version 5.0) before study enrolment;
8. Patients were to have adequate bone marrow, liver and renal: alanine transaminase (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presence of liver metastases], total bilirubin = 1.5 × institutional ULN [= 2.0 x ULN in presence of liver metastases], neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L, proteinuria ¿ 1+ on the dipstick, creatinine = 2.5 x institutional ULN or creatinine clearance of =40 mL/min;
9. Signed written consent form;
10. Patients of reproductive potential, must use adequate contraception methods;
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 62

Exclusion Criteria

1. Radiation therapy or any previous anti-neoplastic systemic treatment within the past 28 days before study enrollment;
2. History of major surgery within 28 days before study enrollment; 3. Known prior malignancies or known brain metastases ( patients with adequately treated basal cell or squamous cell skin cancer,
carcinoma in situ of the cervix, or any other cancer from which the patient had been disease-free for more than 10 years are permitted);
4. Severe acute or chronic medical condition that may impair the ability to participate in the study or may interfere with the interpretation of results;
5. Any contraindication to the administration of aflibercept, irinotecan, 5-fluorouracil or folinic acid;
6. History of any auto-immune or rheumatic disease; any active bacterial or viral infection;
7. History of uncontrolled hypertension and diabetes within 3 months before enrollment;
8. History of daily use of corticosteroids or immune-suppressive medications;
9. Deep vein thrombosis within 4 weeks before treatment;
10. Pregnant and breast-feeding women;
11. Patients of reproductive potential who refuse to use effective methods of contraception;

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess progression free survival associated with the study treatment focusing on its relationship with baseline serum levels of IL-8.;Secondary Objective: To assess: Radiologic Response Rate (rRR), Overall Survival (OS), safety profile, associated with the study treatment and their relationship with baseline levels of IL-8;Primary end point(s): The primary end point of the study is progression free survival (PFS), with the objective to estimate the difference in PFS between the two groups defined on the basis of their baseline IL-8 levels (>= vs. < than median).;Timepoint(s) of evaluation of this end point: 36 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary endpoints of the study are: • Radiologic Response Rate (rRR) • Overall Survival (OS) • Safety profile;Timepoint(s) of evaluation of this end point: 36 months