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Metastatic Colorectal CancerPhase 2NCT05291156

CAVE-2 GOIM Study: a Clinical Study of the Combination of Avelumab Plus Cetuximab as Rechallenge Strategy

A Phase 2 study testing Cetuximab and Avelumab in people with Metastatic Colorectal Cancer, run by University of Campania Luigi Vanvitelli at 24 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Cetuximab and Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
173 participants
Where
24 sitesItaly
Study dates
21 Jul 2022to 1 Jul 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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).
  • No prior immunotherapy

Who cannot join

  • 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:
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  • 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
  • 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)
  • 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.
  • 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.
  • 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).
  • History of hypersensitivity to Polysorbate 80 that led to unacceptable toxicity requiring treatment cessation.
  • Persisting toxicity related to prior therapy of Grade > 1 NCI- CTCAE v 5.0.
  • Known alcohol or drug abuse.
  • 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.
  • 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.
  • 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.
  • 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)
  • Legal incapacity or limited legal capacity.

Trial locations and contacts

24 sites in 1 country.

Fortunato Ciardiello contact

0815666760

fortunato.ciardiello@unicampania.it

Stefania Napolitano contact

stefania.napolitano@unicampania.it

24 sites in 1 country

Italy24 sites, 24 recruiting

  • A.O.U. Ospedali Riuniti

    Ancona

    Rossana Berardi

    Not yet recruiting

  • A.O. San Giuseppe Moscati

    Avellino

    Giuseppe Santabarbara

    Recruiting

  • Centro di Riferimento Oncologico (C.R.O.)

    Aviano

    Elena Ongaro

    Not yet recruiting

  • Fondazione Poliambulanza Istituto Ospedaliero

    Brescia

    Alberto Zaniboni

    Recruiting

  • P.O. Antonio Perrino

    Brindisi

    Saverio Cinieri

    Not yet recruiting

  • Ospedale IRCCS 'Saverio de Bellis'

    Castellana Grotte

    Ivan Roberto Lolli

    Recruiting

  • A.R.N.A.S. Garibaldi - P.O. GaribaldiNesima

    Catania

    Roberto Bordonaro

    Not yet recruiting

  • A.O.U. Careggi

    Florence

    Lorenzo Antonuzzo

    Not yet recruiting

  • Ospedale Policlinico San Martino IRCCS per l'Oncologia

    Genova

    Alberto Sobrero

    Not yet recruiting

  • P.O. 'Vito Fazzi'

    Lecce

    Silvia Leo

    Not yet recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

    Filippo Pietrantonio

    Not yet recruiting

  • Istituto Europeo di Oncologia

    Milan

    Maria Giulia Zampino

    Not yet recruiting

  • A.O.U dell'Università degli Studi della Campania "Luigi Vanvitelli"

    Naples

    Fortunato Ciardiello

    Recruiting

  • IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale"

    Naples

    Antonio Avallone

    Recruiting

  • A.O.U. Policlinico 'P. Giaccone'

    Palermo

    Fabio Fulfaro

    Recruiting

  • ARNAS Civico - Di Cristina-Benfratelli - P. O. 'Civico e Benfratelli'

    Palermo

    Livio Blasi

    Not yet recruiting

  • A.S.P. Ragusa - Ospedale Maria Paternò Arezzo

    Ragusa

    Stefano Cordio

    Not yet recruiting

  • Azienda USL IRCCS di Reggio Emilia

    Reggio Emilia

    Carmine Pinto

    Not yet recruiting

  • Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS

    Roma

    Giampaolo Tortora

    Not yet recruiting

  • Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo

    Evaristo Maiello

    Recruiting

  • Ospedale San Giuseppe Moscati

    Taranto

    Salvatore Pisconti

    Recruiting

  • A.O. Ordine Mauriziano

    Torino

    Massimo Di Maio

    Not yet recruiting

  • A.O. 'Pia Fondazione Cardinale G.Panico'

    Tricase

    Emiliano Tamburini

    Not yet recruiting

  • A.O.U. Integrata di Verona - Policlinico 'Giambattista Rossi'

    Verona

    Davide Melisi

    Recruiting

Other trials in Italy

About this study

Official title: 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.

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.

Read the detailed description

This is a non-profit phase II, open-label, randomized clinical study of the combination of avelumab plus cetuximab as rechallenge strategy in pre-treated RAS, BRAF wild type metastatic colorectal cancer patients treated in first line with chemotherapy in combination with cetuximab and have had a clinical benefit (complete or partial response) from treatment.

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.
Being tested
Cetuximab, Avelumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabDrug

    Also called Erbitux

    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.

  • AvelumabDrug

    Also called Bavencio

    Avelumab will be administered as a 1-hour IV infusion at flat dose of 800 mg every 2-week treatment cycle.

Study groups in NCT05291156
Study groupRoleWhat they receive
Cetuximab + avelumabExperimentalCetuximab + 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.
Receives: Drug: Cetuximab; Drug: Avelumab
CetuximabActive 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.
Receives: Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. OS

    Overall Survival defined as the interval from enrollment to death for every cause.

    Measured: up to 36 months

Secondary outcomes (3)

  1. ORR

    Overall Response Rate (ORR) defined as the proportion of patients who have a partial or complete response to therapy.

    Measured: from screening up to 36 months

  2. PFS

    Progression Free Survival (PFS) defined as the time from random assignment in the clinical trial to disease progression or death from any cause.

    Measured: from screening up to 36 months (from the start of therapy until disease progression or death due to any cause)

  3. Incidence of treatment-related adverse events as assessed by CTCAE v5.0

    Safety profile of the trial drugs as measured by the incidence of AEs, SAEs.

    Measured: up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2022
  2. Study start21 Jul 2022
  3. Primary completion1 Jul 2025 (estimated)
  4. Study completion1 Jul 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients will be randomized (2:1) as follow: * Cetuximab + avelumab * Cetuximab only
Masking
None (open label)
Enrolment
173 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05291156
Sponsor's protocol ID
CAVE 2
Status last verified
Jan 2024
First submitted
1 Mar 2022
Last updated
1 Feb 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 35832541

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cetuximab and Avelumab in people with Metastatic Colorectal Cancer, run by University of Campania Luigi Vanvitelli at 24 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Fortunato Ciardiello (0815666760, fortunato.ciardiello@unicampania.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

OS (time frame: up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05291156, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2024.

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