Squamous Cell Anal CarcinomaPhase 2CARACASNCT03944252
Cetuximab + Avelumab or Avelumab Alone for Unresectable, Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (SCCAC) Progressed After at Least One Line of Systemic Treatment (CARACAS)
A Phase 2 study testing Avelumab and Cetuximab in people with Squamous Cell Anal Carcinoma, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
Trial summary
The standard first line treatment in SCCAC is the association of 5-FU with cisplatin reaching a percentage of survival at 5 years of about 32% (Faivre 1999); in a recent case series of patients affected by SCCAC, the combination of 5-FU and cisplatin as first line treatment produced 34.4% objective response rate (ORR)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Anal Carcinoma
- 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
- 54 participants
- Where
- 1 siteItaly
- Study dates
- 18 Sep 2018to Feb 2022
- 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
- Histologically proven diagnosis of SCCAC;
- Progression on or after first line systemic therapy for surgically unresectable or metastatic disease. Systemic radiosensitizing chemotherapy with curative intent in limited-stage disease should be considered equal to a first line for a patient experiencing progression during or within 6 months of completion;
- Evaluable disease lesion according to RECIST v1.1 criteria;
- Availability of tumor sample (primary and/or metastatic sites);
- Age ≥ 18 years;
- Eastern Cooperative Oncology Group - Performance Status (ECOG PS) ≤ 2;
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- Life expectancy of at least 12 weeks;
- Laboratory Requirements:
- Neutrophils ≥ 1.5 x 109 /L; Platelets ≥ 100 x 109 /L; Hemoglobin ≥ 9 g/dL; Total bilirubin ≤ 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases); Alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases); Creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) or serum creatinine ≤1.5 x UNL;
- HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load has to be undetectable, and they have to be compliant with antiretroviral treatment;
- Negative serum or urine pregnancy test at screening for women of childbearing potential. Female subjects, or male subjects with female partners of child-bearing potential must be willing to use highly effective contraception as approved by the investigator (i.e. barrier contraceptive measure or oral contraception, total abstinence) during the study and until 30 days after last study treatment;
- Written informed consent to the study procedures and to molecular analyses before patients registration;
- Will and ability to comply with the protocol.
Who cannot join
- Previous therapy with any drug targeting T-cell co-regulatory proteins (i.e., immune checkpoint inhibitors);
- Concurrent anticancer treatment or use of any investigational drug within 28 days before the start of the trial treatment;
- Major surgical procedure, open biopsy, or significant traumatic injury occurred within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study;
- History or evidence upon physical examination of CNS disease unless adequately treated. Patients with treated brain metastases are eligible if their lesions were stable and asymptomatic for at least 3 months;
- Neutrophils < 1.5 x 109/L; Platelets < 100 x 109/L; Hemoglobin < 9 g/dL;
- Active uncontrolled infections requiring systemic therapy or other clinically relevant concomitant illness contraindicating therapy administration or putting the patient at high risk for treatment-related toxicities;
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- 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);
- Patients with active autoimmune disease or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent or might potentially affect vital organ function, or require use of immunosuppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use for ≥ 1 month). Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible;
- Current use of immunosuppressive medication, EXCEPT for the following:
- intranasal, inhaled, topical steroids, or 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);
- Prior organ transplantation including allogenic stem-cell transplantation;
- Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines;
- Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma;
- Clinically significant (i.e., 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 cardiac arrhythmia requiring medication;
- Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonia, 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;
- Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable;
- Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma of the skin or cervical cancer in situ;
- Pregnant or lactating women;
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase 2 Trial of Cetuximab and Avelumab or Avelumab Alone for Unresectable, Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (SCCAC) Progressed After at Least One Line of Systemic Treatment
- The standard first line treatment in SCCAC is the association of 5-FU with cisplatin reaching a percentage of survival at 5 years of about 32% (Faivre 1999); in a recent case series of patients affected by SCCAC, the combination of 5-FU and cisplatin as first line treatment produced 34.4% objective response rate (ORR) and a 5 years survival rate of 15% (Sclafani 2017);
- No standard second line treatment exists for SCCAC;
- Cetuximab in association with irinotecan has demonstrated promising results in pretreated patients affected by SCCAC (Lukan 2009). In addition, it was recently tested in stage I-III SCCAC in association with cisplatin plus 5-FU and radiotherapy. Despite not reaching their pre-specified endpoints both studies reported an interesting activity in local control of disease, leading to hypothesize that cetuximab warrant further investigation in new strategies (Garg 2017, Sparano 2017);
- Anti-PD1 treatments such as nivolumab and pembrolizumab showed promising activity in metastatic refractory SCCAC in terms of response rate and disease control with acceptable toxicity profiles (Morris 2017, Ott 2017);
- The induction of immunogenic cell death was recently shown for cetuximab-based regimens (Pozzi 2016) and PD-L1 blockade should lead to NK cells activation enhancing cetuximab ADCC (Concha-Benavente 2015, Concha-Benavente 2016).
On the basis of these considerations, the investigators designed the present randomized phase II trial of avelumab alone or avelumab plus cetuximab for previously treated unresectable locally advanced or metastatic SCCAC.
- Conditions
- Squamous Cell Anal Carcinoma
- Medical subject headings
- Anus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.
CetuximabDrug
cetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| A (avelumab) | Experimental | avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. Receives: Drug: Avelumab |
| B (cetuximab + avelumab) | Experimental | cetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. Receives: Drug: Avelumab; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint is Objective Response Rate (ORR).
The primary endpoint is Objective Response Rate (ORR). 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 Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. The determination of the radiological response will be based on the investigator's reported evaluation.
Measured: Radiological responses will be evaluated starting from cycle 1 day 1 of treatment until disease progression, withdrawal of consent or death for any reason, whichever occurs first assessed up to 12 moths.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start18 Sep 2018
- Primary completionFeb 2021 (estimated)
- Study completionFeb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Anal CarcinomaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico del Nord-Ovest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03944252
- Sponsor's protocol ID
- 2018-000737-12
- Other IDs
- 2018
- Acronym
- CARACAS
- Status last verified
- Jul 2019
- First submitted
- 12 Apr 2019
- Last updated
- 26 Jul 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Prete AA, Manca P, Messina M, Formica V, Frassineti GL, Zampino MG, Corsi DC, Orciuolo C, Prisciandaro M, Bergamo F, Angerilli V, Scartozzi M, Casagrande M, Masi G, Ronzoni M, Morano F, Vettore V, Salmaso R, Rasola C, Maddalena G, Del Bianco P, Milione M, Cremolini C, Fassan M, Pietrantonio F, Lonardi S. Extensive molecular profiling of squamous cell anal carcinoma in a phase 2 trial population: Translational analyses of the "CARACAS" study. Eur J Cancer. 2023 Mar;182:87-97. doi: 10.1016/j.ejca.2022.12.025. Epub 2023 Jan 9.
PubMed 36753836Lonardi S, Prete AA, Morano F, Messina M, Formica V, Corsi DC, Orciuolo C, Frassineti GL, Zampino MG, Casagrande M, Masi G, Ronzoni M, Scartozzi M, Buonadonna A, Mosconi S, Ratti M, Sartore-Bianchi A, Tamburini E, Prisciandaro M, Bergamo F, Spada M, Corallo S, Vettore V, Loupakis F, Fassan M, Del Bianco P, Zagonel V, Pietrantonio F. Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study. J Immunother Cancer. 2021 Nov;9(11):e002996. doi: 10.1136/jitc-2021-002996.
PubMed 34815354
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase 2 Trial of Cetuximab and Avelumab or Avelumab Alone for Unresectable, Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (SCCAC) Progressed After at Least One Line of Systemic Treatment
- ClinicalTrials.gov ID
- NCT03944252
- Acronym / sponsor ID
- CARACAS / 2018-000737-12
- Conditions
- Squamous Cell Anal Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Study start
- 18 Sep 2018 (actual)
- Primary completion
- Feb 2021 (estimated)
- Study completion
- Feb 2022 (estimated)
- First posted
- 9 May 2019 (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.
- The standard first line treatment in SCCAC is the association of 5-FU with cisplatin reaching a percentage of survival at 5 years of about 32% (Faivre 1999); in a recent case series of patients affected by SCCAC, the combination of 5-FU and cisplatin as first line treatment produced 34.4% objective response rate (ORR) and a 5 years survival rate of 15% (Sclafani 2017);
- No standard second line treatment exists for SCCAC;
- Cetuximab in association with irinotecan has demonstrated promising results in pretreated patients affected by SCCAC (Lukan 2009). In addition, it was recently tested in stage I-III SCCAC in association with cisplatin plus 5-FU and radiotherapy. Despite not reaching their pre-specified endpoints both studies reported an interesting activity in local control of disease, leading to hypothesize that cetuximab warrant further investigation in new strategies (Garg 2017, Sparano 2017);
- Anti-PD1 treatments such as nivolumab and pembrolizumab showed promising activity in metastatic refractory SCCAC in terms of response rate and disease control with acceptable toxicity profiles (Morris 2017, Ott 2017);
- The induction of immunogenic cell death was recently shown for cetuximab-based regimens (Pozzi 2016) and PD-L1 blockade should lead to NK cells activation enhancing cetuximab ADCC (Concha-Benavente 2015, Concha-Benavente 2016).
On the basis of these considerations, the investigators designed the present randomized phase II trial of avelumab alone or avelumab plus cetuximab for previously treated unresectable locally advanced or metastatic SCCAC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A (avelumab) | Experimental | Drug: Avelumabavelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. |
| B (cetuximab + avelumab) | Experimental | Drug: Avelumab, Drug: Cetuximabcetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically proven diagnosis of SCCAC;
- Progression on or after first line systemic therapy for surgically unresectable or metastatic disease. Systemic radiosensitizing chemotherapy with curative intent in limited-stage disease should be considered equal to a first line for a patient experiencing progression during or within 6 months of completion;
- Evaluable disease lesion according to RECIST v1.1 criteria;
- Availability of tumor sample (primary and/or metastatic sites);
- Age ≥ 18 years;
Key exclusion criteria (21 listed)
- Previous therapy with any drug targeting T-cell co-regulatory proteins (i.e., immune checkpoint inhibitors);
- Concurrent anticancer treatment or use of any investigational drug within 28 days before the start of the trial treatment;
- Major surgical procedure, open biopsy, or significant traumatic injury occurred within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study;
- History or evidence upon physical examination of CNS disease unless adequately treated. Patients with treated brain metastases are eligible if their lesions were stable and asymptomatic for at least 3 months;
- Neutrophils < 1.5 x 109/L; Platelets < 100 x 109/L; Hemoglobin < 9 g/dL;
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 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. | Drug | A (avelumab), B (cetuximab + avelumab) |
| Cetuximabcetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. | Drug | B (cetuximab + avelumab) |
Primary outcome
Primary endpoint is Objective Response Rate (ORR).
Time frame: Radiological responses will be evaluated starting from cycle 1 day 1 of treatment until disease progression, withdrawal of consent or death for any reason, whichever occurs first assessed up to 12 moths.
The primary endpoint is Objective Response Rate (ORR). 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 Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. The determination of the radiological response will be based on the investigator's reported evaluation.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2019.
- Derived from this study: PubMed 36753836Prete AA, Manca P, Messina M, Formica V, Frassineti GL, Zampino MG, Corsi DC, Orciuolo C, Prisciandaro M, Bergamo F, Angerilli V, Scartozzi M, Casagrande M, Masi G, Ronzoni M, Morano F, Vettore V, Salmaso R, Rasola C, Maddalena G, Del Bianco P, Milione M, Cremolini C, Fassan M, Pietrantonio F, Lonardi S. Extensive molecular profiling of squamous cell anal carcinoma in a phase 2 trial population: Translational analyses of the "CARACAS" study. Eur J Cancer. 2023 Mar;182:87-97. doi: 10.1016/j.ejca.2022.12.025. Epub 2023 Jan 9.
- Derived from this study: PubMed 34815354Lonardi S, Prete AA, Morano F, Messina M, Formica V, Corsi DC, Orciuolo C, Frassineti GL, Zampino MG, Casagrande M, Masi G, Ronzoni M, Scartozzi M, Buonadonna A, Mosconi S, Ratti M, Sartore-Bianchi A, Tamburini E, Prisciandaro M, Bergamo F, Spada M, Corallo S, Vettore V, Loupakis F, Fassan M, Del Bianco P, Zagonel V, Pietrantonio F. Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study. J Immunother Cancer. 2021 Nov;9(11):e002996. doi: 10.1136/jitc-2021-002996.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Squamous Cell Anal Carcinoma, run by Gruppo Oncologico del Nord-Ovest 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 13 inclusion and 21 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 26 Jul 2019. 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?
Results are not available in the source record.
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?
Primary endpoint is Objective Response Rate (ORR). (time frame: Radiological responses will be evaluated starting from cycle 1 day 1 of treatment until disease progression, withdrawal of consent or death for any reason, whichever occurs first assessed up to 12 moths.). 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 NCT03944252, which also lists 2 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 26 Jul 2019; AzTrials last refreshed its copy on 7 Nov 2026.