CAVE-2 GOIM Study: a Clinical Study of the Combination of Avelumab Plus Cetuximab as Rechallenge Strategy
NCT ID: NCT05291156
Last Updated: 2024-02-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
173 participants
INTERVENTIONAL
2022-07-21
2025-07-01
Brief Summary
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Detailed Description
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173 patients will be randomized (2:1) as follows: cetuximab + avelumab (115 patients) or cetuximab only (58 patients). For each patient, before treatment, a blood sample will be obtained and analyzed for circulating free tumorDNA, to identify RAS/BRAF wild type patient to be enrolled. The same procedure will be performed at progression of the disease. Treatment will continue until:
* disease progression.
* significant clinical deterioration
* any criterion for withdrawal from the trial or trial drug is fulfilled
* treatment may continue past the initial determination of disease progression according to 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, that is, no new symptoms or worsening of existing symptoms and no decrease in performance score.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
* Cetuximab + avelumab
* Cetuximab only
TREATMENT
NONE
Study Groups
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Cetuximab + avelumab
Cetuximab + 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
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
Avelumab will be administered as a 1-hour IV infusion at flat dose of 800 mg every 2-week treatment cycle.
Cetuximab
Cetuximab 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.
Cetuximab
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.
Interventions
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Cetuximab
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
Avelumab will be administered as a 1-hour IV infusion at flat dose of 800 mg every 2-week treatment cycle.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Male or female subjects aged ≥ 18 years.
3. Histologically proven diagnosis of colorectal adenocarcinoma.
4. Diagnosis of metastatic disease.
5. RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at screening (according to NGS, Foundation/Roche).
6. 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).
7. Received a second line therapy.
8. More than 4 months since the last dose of cetuximab administered in first line treatment before randomization.
9. Measurable disease according to RECIST criteria v1.1.
10. ECOG PS of 0 to 1 at trial entry.
11. Estimated life expectancy of more than 12 weeks.
12. 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).
13. 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).
14. Adequate renal function defined by an estimated creatinine clearance \> 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
15. 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).
16. No prior immunotherapy
Exclusion Criteria
2. 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.
3. Pregnancy.
4. Breastfeeding.
5. Participation in a clinical study or experimental drug treatment within 30 days before enrollment.
6. 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)
7. 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)
8. Prior organ transplantation, including allogeneic stemcell transplantation
9. Significant acute or chronic infections including, among others:
* Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
* Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
10. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
* Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
* Subjects requiring hormone replacement with corticosteroids are eligible if steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or equivalent prednisone per day.
* Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.
* Active infection requiring systemic therapy.
11. Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone.
12. Known severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 5 Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
13. History of hypersensitivity to Polysorbate 80 that led to unacceptable toxicity requiring treatment cessation.
14. Persisting toxicity related to prior therapy of Grade \> 1 NCI- CTCAE v 5.0.
15. Known alcohol or drug abuse.
16. Clinically significant (that is active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
17. History of keratitis, ulcerative keratitis or severe dry eye. Since contact lent use is also a risk factor for keratitis and ulceration, it is not recommended.
18. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
19. Vaccination within 4 weeks of the first dose of avelumab and cetuximab and while on treatment is prohibited except for administration of inactivated vaccine (i.e. inactivated influenza vaccine)
20. Legal incapacity or limited legal capacity.
18 Years
ALL
No
Sponsors
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University of Campania Luigi Vanvitelli
OTHER
Responsible Party
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Fortunato Ciardiello
Principal Investigator
Principal Investigators
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Fortunato Ciardiello
Role: PRINCIPAL_INVESTIGATOR
A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"
Locations
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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
Countries
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Central Contacts
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Facility Contacts
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Rossana Berardi
Role: primary
Giuseppe Santabarbara
Role: primary
Elena Ongaro
Role: primary
Alberto Zaniboni
Role: primary
Saverio Cinieri
Role: primary
Ivan Roberto Lolli
Role: primary
Roberto Bordonaro
Role: primary
Lorenzo Antonuzzo
Role: primary
Alberto Sobrero
Role: primary
Silvia Leo
Role: primary
Filippo Pietrantonio
Role: primary
Maria Giulia Zampino
Role: primary
Fortunato Ciardiello
Role: primary
Antonio Avallone
Role: primary
Fabio Fulfaro
Role: primary
Livio Blasi
Role: primary
Stefano Cordio
Role: primary
Carmine Pinto
Role: primary
Giampaolo Tortora
Role: primary
Evaristo Maiello
Role: primary
Salvatore Pisconti
Role: primary
Massimo Di Maio
Role: primary
Emiliano Tamburini
Role: primary
Davide Melisi
Role: primary
References
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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.
Other Identifiers
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CAVE 2
Identifier Type: -
Identifier Source: org_study_id
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