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

NCT02296203 | Unknown Phase 2

• 1 other identifier: GONO 10
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 9

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.

Conditions

Metastatic Colorectal Cancer

Keywords

cetuximab rechallenge

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

cetuximab and irinotecan

EXPERIMENTAL

Drug: cetuximab; Drug: irinotecan

Interventions

cetuximab DRUG

cetuximab and irinotecan

irinotecan DRUG

cetuximab and irinotecan

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (9)

AUSL DI FROSINONE - FROSINONE (FR) ONCOLOGIA MEDICA U.O. Oncologia Medica

Frosinone, 03100, Italy

Location

Irccs Istituto Oncologico Veneto (Iov) - Padova (Pd) Oncologia Medica

Padua, 35128, Italy

Location

Azienda Ospedaliero Universitaria Di Parma - U.O.Oncologia Medica

Parma, Italy

Location

A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica

Pisa, 56126, Italy

Location

AUSL 5 DI PISA - PISA (PI) ONCOLOGIA MEDICA oncologia medica Osp Lotti Pontedera

Pontedera, 56100, Italy

Location

Ospedale Fatebenefratelli

Roma, 00186, Italy

Location

Azienda Policlinico Umberto I - Oncologia Medica

Roma, Italy

Location

Campus Biomedico

Roma, Italy

Location

A.O. Universitaria S.Maria Della Misericordia Di Udine

Udine, 33100, Italy

Location

Related Publications (3)

• Ciardiello D, Martinelli E, Troiani T, Mauri G, Rossini D, Martini G, Napolitano S, Famiglietti V, Del Tufo S, Masi G, Santini D, Avallone A, Pietrantonio F, Lonardi S, Di Maio M, Zampino MG, Fazio N, Bardelli A, Siena S, Cremolini C, Sartore-Bianchi A, Ciardiello F. Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer: A Nonrandomized Controlled Trial. JAMA Netw Open. 2024 Apr 1;7(4):e245635. doi: 10.1001/jamanetworkopen.2024.5635.

  PMID: 38592721 DERIVED

• Martini G, Ciardiello D, Famiglietti V, Rossini D, Antoniotti C, Troiani T, Napolitano S, Esposito L, Latiano TP, Maiello E, Del Re M, Lonardi S, Aprile G, Santini D, Masi G, Avallone A, Normanno N, Pietrantonio F, Pinto C, Ciardiello F, Cremolini C, Martinelli E. Cetuximab as third-line rechallenge plus either irinotecan or avelumab is an effective treatment in metastatic colorectal cancer patients with baseline plasma RAS/BRAF wild-type circulating tumor DNA: Individual patient data pooled analysis of CRICKET and CAVE trials. Cancer Med. 2023 Apr;12(8):9392-9400. doi: 10.1002/cam4.5699. Epub 2023 Mar 7.

  PMID: 36880426 DERIVED

• 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.

  PMID: 30476968 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Irinotecan

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Alfredo Falcone, MD, PhD

  U.O. Oncologia Medica 2 Universitaria, Università di Pisa - AOUP, Polo Oncologico, Area Vasta Nord-Ovest, Istituto Toscano Tumori

  PRINCIPAL INVESTIGATOR

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: October 15, 2014
• First Posted: November 20, 2014
• Study Start: October 1, 2014
• Primary Completion: June 19, 2017
• Study Completion: June 15, 2018
• Last Updated: February 15, 2018

Record last verified: 2018-02

Locations

IT (9)