CAVE-2 GOIM Study: a Clinical Study of the Combination of Avelumab Plus Cetuximab as Rechallenge Strategy
CAVE-2 (Cetuximab-AVElumab) mCRC: A Phase II Randomized Clinical Study of the Combination of Avelumab Plus Cetuximab as Rechallenge Strategy in Pre-treated RAS/BRAF Wild Type Metastatic Colorectal Cancer Patients.
1 other identifier
interventional
173
1 country
24
Brief Summary
This is a non-profit phase II, randomized clinical study of the combination of avelumab plus cetuximab as rechallenge strategy, compared to cetuximab alone, in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Patients have been treated in first line with chemotherapy in combination with cetuximab and have had a clinical benefit (complete or partial response) from treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2022
Typical duration for phase_2
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 1, 2022
CompletedFirst Posted
Study publicly available on registry
March 22, 2022
CompletedStudy Start
First participant enrolled
July 21, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2025
CompletedFebruary 1, 2024
January 1, 2024
2.9 years
March 1, 2022
January 31, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
OS
Overall Survival defined as the interval from enrollment to death for every cause.
up to 36 months
Secondary Outcomes (3)
ORR
from screening up to 36 months
PFS
from screening up to 36 months (from the start of therapy until disease progression or death due to any cause)
Incidence of treatment-related adverse events as assessed by CTCAE v5.0
up to 36 months
Study Arms (2)
Cetuximab + avelumab
EXPERIMENTALCetuximab + avelumab (115 patients) - cetuximab at 400 mg/m2, as loading dose, and, subsequently, at 250 mg/m2 weekly, and avelumab was given intravenously at flat dose of 800 mg, once every 2 weeks. Treatment will continue until disease progression, significant clinical deterioration, unacceptable toxicity, any criterion for withdrawal from the trial or trial drug is fulfilled. Treatment may continue past the initial determination of disease progression per RECIST 1.1 if the subject's performance status has remained stable, and if in the opinion of the Investigator, the subject will benefit from continued treatment and if other criteria are fulfilled as outlined in the protocol.
Cetuximab
ACTIVE COMPARATORCetuximab only (58 patients) - cetuximab at 400 mg/m2 intravenously, as loading dose, and, subsequently, at 250 mg/m2 weekly. Treatment will continue until disease progression, significant clinical deterioration, unacceptable toxicity, any criterion for withdrawal from the trial or trial drug is fulfilled. Treatment may continue past the initial determination of disease progression per RECIST 1.1 if the subject's performance status has remained stable, and if in the opinion of the Investigator, the subject will benefit from continued treatment and if other criteria are fulfilled as outlined in the protocol.
Interventions
Cetuximab will be administered at 1st dose at 400 mg/m2 by i.v. infusion over 120 minutes. The 2nd dose and subsequent doses will be performed at 250 mg/ m2 by i.v. infusion over 60 minutes, every week.
Avelumab will be administered as a 1-hour IV infusion at flat dose of 800 mg every 2-week treatment cycle.
Eligibility Criteria
You may qualify if:
- Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.
- Male or female subjects aged ≥ 18 years.
- Histologically proven diagnosis of colorectal adenocarcinoma.
- Diagnosis of metastatic disease.
- RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at screening (according to NGS, Foundation/Roche).
- Efficacy of a first line therapy containing cetuximab with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1).
- Received a second line therapy.
- More than 4 months since the last dose of cetuximab administered in first line treatment before randomization.
- Measurable disease according to RECIST criteria v1.1.
- ECOG PS of 0 to 1 at trial entry.
- Estimated life expectancy of more than 12 weeks.
- Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).
- Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
- Adequate renal function defined by an estimated creatinine clearance \> 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
- Effective contraception for both male and female subjects throughout the study and for at least 2 months after last study treatment administration if the risk of conception exists (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device, or use of oral female contraceptive. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately).
- +1 more criteria
You may not qualify if:
- Any contraindication to cetuximab and/or avelumab.
- Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix.
- Pregnancy.
- Breastfeeding.
- Participation in a clinical study or experimental drug treatment within 30 days before enrollment.
- 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
- Intranasal, inhaled, topical steroids,
- Local steroid injection (e.g., intra-articular injection)
- Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- All subjects with brain metastases, except those meeting the following criteria:
- Brain metastases have been treated locally
- No ongoing neurological symptoms related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
- Prior organ transplantation, including allogeneic stemcell transplantation
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
A.O.U. Ospedali Riuniti
Ancona, Italy
A.O. San Giuseppe Moscati
Avellino, Italy
Centro di Riferimento Oncologico (C.R.O.)
Aviano, Italy
Fondazione Poliambulanza Istituto Ospedaliero
Brescia, Italy
P.O. Antonio Perrino
Brindisi, Italy
Ospedale IRCCS 'Saverio de Bellis'
Castellana Grotte, Italy
A.R.N.A.S. Garibaldi - P.O. GaribaldiNesima
Catania, Italy
A.O.U. Careggi
Florence, Italy
Ospedale Policlinico San Martino IRCCS per l'Oncologia
Genova, Italy
P.O. 'Vito Fazzi'
Lecce, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Istituto Europeo di Oncologia
Milan, Italy
A.O.U dell'Università degli Studi della Campania "Luigi Vanvitelli"
Napoli, Italy
IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale"
Napoli, Italy
A.O.U. Policlinico 'P. Giaccone'
Palermo, Italy
ARNAS Civico - Di Cristina-Benfratelli - P. O. 'Civico e Benfratelli'
Palermo, Italy
A.S.P. Ragusa - Ospedale Maria Paternò Arezzo
Ragusa, Italy
Azienda USL IRCCS di Reggio Emilia
Reggio Emilia, Italy
Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS
Roma, Italy
Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Italy
Ospedale San Giuseppe Moscati
Taranto, Italy
A.O. Ordine Mauriziano
Torino, Italy
A.O. 'Pia Fondazione Cardinale G.Panico'
Tricase, Italy
A.O.U. Integrata di Verona - Policlinico 'Giambattista Rossi'
Verona, Italy
Related Publications (1)
Napolitano S, Martini G, Ciardiello D, Di Maio M, Normanno N, Avallone A, Martinelli E, Maiello E, Troiani T, Ciardiello F. CAVE-2 (Cetuximab-AVElumab) mCRC: A Phase II Randomized Clinical Study of the Combination of Avelumab Plus Cetuximab as a Rechallenge Strategy in Pre-Treated RAS/BRAF Wild-Type mCRC Patients. Front Oncol. 2022 Jun 27;12:940523. doi: 10.3389/fonc.2022.940523. eCollection 2022.
PMID: 35832541DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fortunato Ciardiello
A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 1, 2022
First Posted
March 22, 2022
Study Start
July 21, 2022
Primary Completion
July 1, 2025
Study Completion
July 1, 2025
Last Updated
February 1, 2024
Record last verified: 2024-01