Avelumab Plus Cetuximab in Pre-treated RAS Wild Type Metastatic Colorectal Cancer

NCT04561336 | Completed Phase 2 DMC

• 2 other identifiers: MS 100070-00282017-004392-32
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Colorectal Cancer; RAS Wild Type

Outcome Measures

Primary Outcomes (1)

• overall survival

  24 months

Study Arms (1)

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.

Drug: Avelumab; Drug: Cetuximab

Interventions

Avelumab DRUG

avelumab in combination with cetuximab

avelumab plus cetuximab

Cetuximab DRUG

avelumab in combination with cetuximab

avelumab plus cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 3.Histologically proven diagnosis of colorectal adenocarcinoma.
• \. 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).
• \. 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).
• \. 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.
• \. No prior immunotherapy

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 4.Breastfeeding
• \. Participation in a clinical study or experimental drug treatment within 30 days.
• \. 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, 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:

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

Università della Campania Luigi Vanvitelli

Napoli, 80131, Italy

Location

Related Publications (3)

• 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.

  PMID: 38592721 DERIVED

• Martini 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.

  PMID: 36880426 DERIVED

• Martinelli 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.

  PMID: 34382998 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

avelumab; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Fortunato Ciardiello, MD

  Università della Campania L Vanvitelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Model Details: combination treatment

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 23, 2020
• Study Start: August 10, 2018
• Primary Completion: November 14, 2021
• Study Completion: November 14, 2021
• Last Updated: May 5, 2022

Record last verified: 2022-05

Locations

IT (1)