Clinical trial NCT02296203: Cetuximab Rechallenge in Irinotecan-pretreated mCRC, KRAS, NRAS and BRAF Wild-type Treated in 1st Line With Anti-EGFR Therapy (CRICKET).
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: cetuximab rechallenge
Lead sponsor: Gruppo Oncologico del Nord-Ovest
Sponsor class: OTHER
First posted: 2014-11-20
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: percentage of patients achieving a decrease equal or more than 30% in the sum of the longest diameters of target lesions
timeFrame: evaluation every 8 weeks until 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Frosinone
country: Italy
facility: AUSL DI FROSINONE - FROSINONE (FR) ONCOLOGIA MEDICA U.O. Oncologia Medica
city: Padova
country: Italy
facility: Irccs Istituto Oncologico Veneto (Iov) - Padova (Pd) Oncologia Medica
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria Di Parma - U.O.Oncologia Medica
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica
city: Pontedera
country: Italy
facility: AUSL 5 DI PISA - PISA (PI) ONCOLOGIA MEDICA oncologia medica Osp Lotti Pontedera
city: Roma
country: Italy
facility: Ospedale Fatebenefratelli
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I - Oncologia Medica
city: Roma
country: Italy
facility: Campus Biomedico
city: Udine
country: Italy
facility: A.O. Universitaria S.Maria Della Misericordia Di Udine
Study officials:
affiliation: U.O. Oncologia Medica 2 Universitaria, Università di Pisa - AOUP, Polo Oncologico, Area Vasta Nord-Ovest, Istituto Toscano Tumori
name: Alfredo Falcone, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.