Cetuximab Rechallenge in Irinotecan-pretreated mCRC, KRAS, NRAS and BRAF Wild-type Treated in 1st Line With Anti-EGFR Therapy (CRICKET). (CRICKET)

A PHASE II SINGLE-ARM STUDY OF CETUXIMAB PLUS IRINOTECAN AS RECHALLENGE 3RD-LINE TREATMENT OF KRAS, NRAS AND BRAF WILD-TYPE IRINOTECAN-PRETREATED METASTATIC COLORECTAL CANCER PATIENTS PROGRESSING AFTER AN INITIAL RESPONSE TO A 1ST-LINE CETUXIMAB-CONTAINING THERAPY AND A STANDARD 2ND-LINE

This is a multicentric, phase II single-arm study in which KRAS, NRAS and BRAF wild-type, irinotecan-resistant metastatic colorectal cancer patients progressing after an initial response to a first-line cetuximab-containing therapy, receive a rechallenge third-line treatment with cetuximab plus irinotecan.

Study Overview

• Status: Unknown
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: cetuximab; Drug: irinotecan

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Frosinone, Italy, 03100
    • AUSL DI FROSINONE - FROSINONE (FR) ONCOLOGIA MEDICA U.O. Oncologia Medica
  • Padova, Italy, 35128
    • Irccs Istituto Oncologico Veneto (Iov) - Padova (Pd) Oncologia Medica
  • Parma, Italy
    • Azienda Ospedaliero Universitaria Di Parma - U.O.Oncologia Medica
  • Pisa, Italy, 56126
    • A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica
  • Pontedera, Italy, 56100
    • AUSL 5 DI PISA - PISA (PI) ONCOLOGIA MEDICA oncologia medica Osp Lotti Pontedera
  • Roma, Italy
    • Campus Biomedico
  • Roma, Italy, 00186
    • Ospedale Fatebenefratelli
  • Roma, Italy
    • Azienda Policlinico Umberto I - Oncologia Medica
  • Udine, Italy, 33100
    • A.O. Universitaria S.Maria Della Misericordia Di Udine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically proven diagnosis of colorectal adenocarcinoma;
• RAS and BRAF wild-type status;
• First-line irinotecan-based (FOLFIRI or FOLFOXIRI) cetuximab-containing therapy producing at least a partial response;
• First-line progression-free survival in response to cetuximab-containing therapy ≥6 months;
• Documentation of progression to first-line cetuximab within 4 weeks after last cetuximab administration;
• Time between the end of first-line therapy and the start of third-line treatment with cetuximab plus irinotecan ≥4 months;
• Second-line oxaliplatin-based (FOLFOXIRI, FOLFOX or XELOX) bevacizumab-containing therapy;
• Documentation of progression to second-line treatment;
• Measurable disease according to RECIST criteria v1.1;
• Have tumor tissue (of primary tumor and metastases or at least one of the two) available for biomarker analysis;
• Male or female patients > 18 years of age;
• ECOG Performance Status ≤ 2;
• Life expectancy of at least 3 months;
• Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment;
• 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 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, such as a two-barrier method or one-barrier method with spermicidal or intrauterine device. This requirement begins 2 weeks before receiving the first trial treatment and ends 6 months after receiving the last treatment;
• Signed informed consent obtained before any study specific procedure.

Exclusion Criteria:

• Active uncontrolled infections or active disseminated intravascular coagulation;
• Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix;
• Fertile women (< 12 months after last menstruation) and men of childbearing potential not willing to use effective means of contraception
• Women who are pregnant or are breastfeeding;
• Previous grade 3/4 infusion related reaction to cetuximab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cetuximab and irinotecan	Drug: cetuximab; Drug: irinotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of patients achieving a decrease equal or more than 30% in the sum of the longest diameters of target lesions	ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria. The determination of clinical response will be based on investigator-reported measurements. Responses will be evaluated with a chest and abdominal computed tomography (CT) scan every 8 weeks. Patients who do not have an on-study assessment will be included in the analysis as non-responders.	evaluation every 8 weeks until 48 weeks

Collaborators and Investigators

• Sponsor: Gruppo Oncologico del Nord-Ovest
• Investigators: Principal Investigator: Alfredo Falcone, MD, PhD, U.O. Oncologia Medica 2 Universitaria, Università di Pisa - AOUP, Polo Oncologico, Area Vasta Nord-Ovest, Istituto Toscano Tumori

Publications and helpful links

General Publications

• Cremolini C, Rossini D, Dell'Aquila E, Lonardi S, Conca E, Del Re M, Busico A, Pietrantonio F, Danesi R, Aprile G, Tamburini E, Barone C, Masi G, Pantano F, Pucci F, Corsi DC, Pella N, Bergamo F, Rofi E, Barbara C, Falcone A, Santini D. Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan: A Phase 2 Single-Arm Clinical Trial. JAMA Oncol. 2019 Mar 1;5(3):343-350. doi: 10.1001/jamaoncol.2018.5080.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 19, 2017
• Study Completion (Anticipated): June 15, 2018

Study Registration Dates

• First Submitted: October 15, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 20, 2014

Study Record Updates

• Last Update Posted (Actual): February 15, 2018
• Last Update Submitted That Met QC Criteria: February 14, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: cetuximab rechallenge
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Cetuximab
• Other Study ID Numbers: GONO 10