Metastatic Colorectal CancerPhase 2NCT04561336
Avelumab Plus Cetuximab in Pre-treated RAS Wild Type Metastatic Colorectal Cancer
A Phase 2 study testing Avelumab and Cetuximab in people with Metastatic Colorectal Cancer and RAS Wild Type, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
Trial summary
This is a non-profit phase II, open-label, single-arm study of cetuximab plus avelumab in patients with RAS WT mCRC treated in first line with chemotherapy in combination with an anti- EGFR drug that have had a clinical benefit (complete or partial response) from treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, RAS Wild Type
- What is being tested?
- Avelumab and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteItaly
- Study dates
- 10 Aug 2018to 14 Nov 2021
- 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 3.Histologically proven diagnosis of colorectal adenocarcinoma.
- 4. Diagnosis of metastatic disease 5. RAS (NRAS and KRAS exon 2,3 and 4) wild-type in tissue at initial diagnosis. 6. Efficacy of a first line therapy containing an anti-EGFR agent (panitumumab or cetuximab) with a major response achieved (complete or partial response).
- 7. A second line therapy. 8. More than 4 months from last dose of anti-EGFR agent 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 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.) Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists.
- 16. No prior immunotherapy
Who cannot join
- Subjects are not eligible for this trial if they fulfill any of the following exclusion criteria:
- 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 4.Breastfeeding
- 5. Participation in a clinical study or experimental drug treatment within 30 days.
- 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:
Show all 25Show fewer
- 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, and
- No ongoing neurological symptoms that are 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 stem-cell transplantation 9. Significant acute or chronic infections including, among others:
- Known history of testing 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 the 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 v4.03 Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more feauters 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 4.03.
- 15. Known alcohol or drug abuse. 16. Clinically significant (that is active) cardioavscular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, comgestive heart failure (New York Heart Association Classification Class≥II), or serious uncontrolled cardiac arrhytmia requiring medication 17. 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.
- 18. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CAVE (Cetuximab-AVElumab) mCRC: A Single Arm Phase II Clinical Study of the Combination of Avelumab Plus Cetuximab in Pre-treated RAS Wild Type Metastatic Colorectal Cancer Patients
This is a non-profit phase II, open-label, single-arm study of cetuximab plus avelumab in patients with RAS WT mCRC treated in first line with chemotherapy in combination with an anti- EGFR drug that have had a clinical benefit (complete or partial response) from treatment.
Read the detailed description
The primary objective of the study is to evaluate the efficacy (OS) of avelumab and cetuximab combined in pre-treated RAS wild type metastatic colorectal cancer patients. Tumor measurements by computed tomography (CT) scan or magnetic resonance imaging (MRI) will be performed every 8 weeks from the beginning of treatment to determine response to treatment. Response will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
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.
- Conditions
- Metastatic Colorectal Cancer, RAS Wild Type
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
avelumab in combination with cetuximab
CetuximabDrug
avelumab in combination with cetuximab
| Study group | Role | What they receive |
|---|---|---|
| avelumab plus cetuximab | Experimental | avelumab at a dose of 10 mg/kg once every 2 weeks plus cetuximab at a starting dose of 400 mg/m2 by i.v.infusion over 120 minutes at first dose and at the dose of 250 mg/ m2 by i.v.infusion over 60 minutes for subsequent infusions every week. Receives: Drug: Avelumab; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall survival
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2020
- Study start10 Aug 2018
- Primary completion14 Nov 2021
- Study completion14 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Model description
- combination treatment
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fortunato Ciardiello, University of Campania Luigi Vanvitelli
- Investigators
- Fortunato Ciardiello, MD, Principal investigator, Università della Campania L Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04561336
- Sponsor's protocol ID
- MS 100070-0028
- Other IDs
- 2017-004392-32, 2017
- Status last verified
- May 2022
- First submitted
- 17 Sep 2020
- Last updated
- 5 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38592721Martini 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.
PubMed 36880426Martinelli E, Martini G, Famiglietti V, Troiani T, Napolitano S, Pietrantonio F, Ciardiello D, Terminiello M, Borrelli C, Vitiello PP, De Braud F, Morano F, Avallone A, Normanno N, Nappi A, Maiello E, Latiano T, Falcone A, Cremolini C, Rossini D, Santabarbara G, Pinto C, Santini D, Cardone C, Zanaletti N, Di Liello A, Renato D, Esposito L, Marrone F, Ciardiello F. Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial. JAMA Oncol. 2021 Oct 1;7(10):1529-1535. doi: 10.1001/jamaoncol.2021.2915.
PubMed 34382998
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CAVE (Cetuximab-AVElumab) mCRC: A Single Arm Phase II Clinical Study of the Combination of Avelumab Plus Cetuximab in Pre-treated RAS Wild Type Metastatic Colorectal Cancer Patients
- ClinicalTrials.gov ID
- NCT04561336
- Acronym / sponsor ID
- MS 100070-0028
- Conditions
- Metastatic Colorectal Cancer, RAS Wild Type
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- 10 Aug 2018 (actual)
- Primary completion
- 14 Nov 2021 (actual)
- Study completion
- 14 Nov 2021 (actual)
- First posted
- 23 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a non-profit phase II, open-label, single-arm study of cetuximab plus avelumab in patients with RAS WT mCRC treated in first line with chemotherapy in combination with an anti- EGFR drug that have had a clinical benefit (complete or partial response) from treatment.
Detailed description
The primary objective of the study is to evaluate the efficacy (OS) of avelumab and cetuximab combined in pre-treated RAS wild type metastatic colorectal cancer patients. Tumor measurements by computed tomography (CT) scan or magnetic resonance imaging (MRI) will be performed every 8 weeks from the beginning of treatment to determine response to treatment. Response will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- combination treatment
| Arm | Type | Receives |
|---|---|---|
| avelumab plus cetuximab | Experimental | Drug: Avelumab, Drug: Cetuximabavelumab at a dose of 10 mg/kg once every 2 weeks plus cetuximab at a starting dose of 400 mg/m2 by i.v.infusion over 120 minutes at first dose and at the dose of 250 mg/ m2 by i.v.infusion over 60 minutes for subsequent infusions every week. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 3.Histologically proven diagnosis of colorectal adenocarcinoma.
- 4. Diagnosis of metastatic disease 5. RAS (NRAS and KRAS exon 2,3 and 4) wild-type in tissue at initial diagnosis. 6. Efficacy of a first line therapy containing an anti-EGFR agent (panitumumab or cetuximab) with a major response achieved (complete or partial response).
- 7. A second line therapy. 8. More than 4 months from last dose of anti-EGFR agent 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).
Key exclusion criteria (25 listed)
- Subjects are not eligible for this trial if they fulfill any of the following exclusion criteria:
- 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 4.Breastfeeding
- 5. Participation in a clinical study or experimental drug treatment within 30 days.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Avelumabavelumab in combination with cetuximab | Drug | avelumab plus cetuximab |
| Cetuximabavelumab in combination with cetuximab | Drug | avelumab plus cetuximab |
Primary outcome
overall survival
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2022.
- Derived from this study: PubMed 38592721Ciardiello 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.
- Derived from this study: PubMed 36880426Martini 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.
- Derived from this study: PubMed 34382998Martinelli E, Martini G, Famiglietti V, Troiani T, Napolitano S, Pietrantonio F, Ciardiello D, Terminiello M, Borrelli C, Vitiello PP, De Braud F, Morano F, Avallone A, Normanno N, Nappi A, Maiello E, Latiano T, Falcone A, Cremolini C, Rossini D, Santabarbara G, Pinto C, Santini D, Cardone C, Zanaletti N, Di Liello A, Renato D, Esposito L, Marrone F, Ciardiello F. Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial. JAMA Oncol. 2021 Oct 1;7(10):1529-1535. doi: 10.1001/jamaoncol.2021.2915.
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fortunato Ciardiello, MD principal investigator
Università della Campania L Vanvitelli
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avelumab and Cetuximab in people with Metastatic Colorectal Cancer and RAS Wild Type, run by University of Campania Luigi Vanvitelli at 1 site 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 7 inclusion and 25 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: finished, as of the sponsor's last update on 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall survival (time frame: 24 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 NCT04561336, which also lists 3 linked publications.
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 5 May 2022.