Cetuximab as Salvage Therapy in Patients With Neo Wild-type RAS/RAF Metastatic Colorectal Cancer With Liver Metastases.

NCT04189055 | Unknown Phase 2 DMC

• 1 other identifier: FBH-001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the efficacy of cetuximab or cetuximab-irinotecan in patients with neo wild-type colorectal cancer who have been previously treated for metastatic disease. Patients will be included in cohort #1 or cohort #2. The inclusion in cohort #2 will start when the results of the cohort #1 are available. Patient will receive either cetuximab alone (cohort #1) or cetuximab with irinotecan (cohort #2).

Conditions

Cancer Colorectal

Keywords

Liver metastasis; KRAS; NRAS

Outcome Measures

Primary Outcomes (1)

• response rate

  Tumor measurements will be obtained at baseline and every 8 weeks following treatment initiation. At the investigator's discretion, tumor assessments may be repeated at any time if progressive disease is suspected. Tumor response and progression will be assessed by the Investigator using RECIST v1.1.

  4 months

Secondary Outcomes (4)

• Overall survival

  time interval from inclusion to the date of death from any cause. Assessed up to 12 months after the beginning of the study

• Progression-free survival

  the time interval from inclusion to the date of first documented disease progression or death from any cause, whichever occurs first. Assessed up to 12 months after the beginning of the study

• Disease Control rate

  from baseline until end of treatment, assessed up to 12 months after the beginning of the study

• Tolerance

  Assessed from study entry to 1 month after last study drug administration, assessed up to 12 months after the beginning of the study

Other Outcomes (1)

• Tumor biomarkers

  Assessed from study entry to end of study treatment, assessed up to 12 months after the beginning of the study

Study Arms (2)

Cohort #1

EXPERIMENTAL

Cetuximab monotherapy (500mg/m² IV, day 1)

Drug: Cetuximab

Cohort #2

EXPERIMENTAL

Cetuximab and irinotecan (cetuximab 500mg/m² IV, day 1; irinotecan 180mg/m² IV, day 1).

Drug: Cetuximab; Drug: Irinotecan

Interventions

Cetuximab DRUG

Cetuximab 500mg/m² IV, day 1

Also known as: Erbitux

Cohort #1; Cohort #2

Irinotecan DRUG

Irinotecan 180mg/m² IV, day 1

Also known as: Campto

Cohort #2

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent and stated willingness to comply with all study procedures and availability for the duration of the study,
• Male or female subjects, ≥18 years of age,
• ECOG performance status (ECOG PS, Appendix 15.1) ≤2,
• Unresectable metastatic RAS mutant (either KRAS or NRAS tumor gene mutation) colorectal cancer,
• At least one (≥1) measurable and/or evaluable liver metastasis,
• Prior therapy (resistant or intolerant) with fluoropyrimidines, oxaliplatin, irinotecan and antiangiogenic agent (ie, bevacizumab and/or aflibercept),
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
• Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL Adequate renal function: serum creatinine clearance (MDRD) ≥ 50 mL/min/1,73 m2 Adequate liver function: serum bilirubin ≤1.5x upper normal limit (ULN), alkaline phosphatase \<5xULN, AST and ALT ≤5xULN, Adequate serum electrolyte levels (magnesium, potassium, calcium) prior to initiation of study treatment,
• Negative pregnancy test within 7 days prior to initiation of the study drug for female patients of childbearing potential,
• Effective contraception for both male and female subjects if the risk of conception exists
• Registration in a national health care system.

You may not qualify if:

• Known allergy or hypersensitivity reactions to any study drug,
• Women who are pregnant or breastfeeding,
• Inability to comply with study and follow-up procedures as judged by the Investigator,
• Patient with BRAF mutant colorectal cancer
• History of interstitial lung disease
• Treatment with strong CYP3A4-enzyme inducers such as anticonvulsants (phenytoin, phenobarbital or carbamazepine), rifampin, rifabutin and St. John's wort for patients of cohort #2
• Treatment with strong CYP3A4-enzyme inhibitors (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) for patients of cohort #2
• Treatment with strong UGT1A inhibitors (e.g. atazanavir, gemfibrozil, indinavir) for patients of cohort # 2
• Patients of cohort #2 with known UGT1A deficiency
• Uncontrolled illness, including but not limited to ongoing bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination/ clinical laboratory finding that leads to a reasonable suspicion of a disease/condition that contraindicates the use of any of investigational drugs that may affect the interpretation of the results, or that may render the subject at high risk of treatment complications.
• Patient with current intestinal obstruction or history of chronic inflammatory bowel disease
• Subjects under guardianship, curatorship or judicial protection

Sponsors & Collaborators

• Hôpital Franco-Britannique-Fondation Cognacq-Jay: lead

Study Sites (1)

Franco-British Hospital - GCS IHFB Cognacq-Jay

Levallois-Perret, 92300, France

RECRUITING

Related Publications (9)

• Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008 Apr 1;26(10):1626-34. doi: 10.1200/JCO.2007.14.7116. Epub 2008 Mar 3.

  PMID: 18316791 BACKGROUND

• Andre T, Blons H, Mabro M, Chibaudel B, Bachet JB, Tournigand C, Bennamoun M, Artru P, Nguyen S, Ebenezer C, Aissat N, Cayre A, Penault-Llorca F, Laurent-Puig P, de Gramont A; GERCOR. Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study. Ann Oncol. 2013 Feb;24(2):412-419. doi: 10.1093/annonc/mds465. Epub 2012 Oct 5.

  PMID: 23041588 BACKGROUND

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. doi: 10.1056/NEJMoa033025.

  PMID: 15269313 BACKGROUND

• Elez E, Kocakova I, Hohler T, Martens UM, Bokemeyer C, Van Cutsem E, Melichar B, Smakal M, Csoszi T, Topuzov E, Orlova R, Tjulandin S, Rivera F, Straub J, Bruns R, Quaratino S, Tabernero J. Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Ann Oncol. 2015 Jan;26(1):132-140. doi: 10.1093/annonc/mdu474. Epub 2014 Oct 15.

  PMID: 25319061 BACKGROUND

• Hecht JR, Patnaik A, Berlin J, Venook A, Malik I, Tchekmedyian S, Navale L, Amado RG, Meropol NJ. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer. 2007 Sep 1;110(5):980-8. doi: 10.1002/cncr.22915.

  PMID: 17671985 BACKGROUND

• Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8. doi: 10.1056/NEJMoa071834.

  PMID: 18003960 BACKGROUND

• Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. doi: 10.1056/NEJMoa0804385.

  PMID: 18946061 BACKGROUND

• Pfeiffer P, Nielsen D, Bjerregaard J, Qvortrup C, Yilmaz M, Jensen B. Biweekly cetuximab and irinotecan as third-line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin and 5-fluorouracil. Ann Oncol. 2008 Jun;19(6):1141-5. doi: 10.1093/annonc/mdn020. Epub 2008 Feb 14.

  PMID: 18281264 BACKGROUND

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Cetuximab; Irinotecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Benoist CHIBAUDEL, MD

  Franco-British Hospital - GCS IHFB Cognacq-Jay

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benoist CHIBAUDEL, MD

CONTACT

0147595965; benoist.chibaudel@ihfb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2019
• First Posted: December 6, 2019
• Study Start: January 7, 2020
• Primary Completion: April 1, 2024
• Study Completion: July 1, 2024
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)