Modified FOLFOXIRI Plus Target Therapy as a First Line Treatment for Advanced Colorectal Cancer a Prospective Phase Two Study

NCT06575127 | Recruiting Phase 2 FDA Drug

• 1 other identifier: FOXIRI
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective Phase II study aims to evaluate the efficacy and safety of a modified FOLFOXIRI regimen in the treatment of metastatic colorectal cancer (MCRC). FOLFOXIRI, though effective, is known for its high toxicity, necessitating close monitoring and dose adjustments. . The primary endpoint is to assess the impact on the objective response rate and evaluate both acute and delayed toxicity. The secondary endpoints include studying the treatment's effectiveness as conversion therapy, along with disease-free survival (DFS) and overall survival (OS). The tertiary endpoint focuses on evaluating predictive and prognostic factors of significance. This study seeks to balance the efficacy of FOLFOXIRI with a modified dose to minimize toxicity while maintaining therapeutic benefits, providing a potentially safer and effective option for patients with MCRC.

Conditions

Neoplasm Malignant; Colon Cancer Stage 4

Keywords

Colon Cancer; MCRC; FOLFOXIRI

Outcome Measures

Primary Outcomes (2)

• Treatment-related adverse events

  evaluate treatment-related acute and delayed toxicity

  12 months

• Objective Response Rate

  To assess the impact of the treatment on the objective response rate

  6 months

Secondary Outcomes (3)

• Conversion therapy

  4 months

• Progression free survival

  12 months

• Overall survival

  24 months

Other Outcomes (1)

• Prognostic and predictive values

  24 month

Study Arms (1)

modified FOLFOXIRI plus target therapy

EXPERIMENTAL

* Pre-Treatment Medications: 1. Atropine SC: Administered before irinotecan infusion to prevent side effects. 2. High-Risk Anti-Emetics Regimen: Used to prevent acute and delayed vomiting. * Chemotherapy Regimen: All eligible patients will receive the modified FOLFOXIRI regimen as follows: * Oxaliplatin: 85 mg/m² IV over 2 hours (Day 1) * Irinotecan: 150 mg/m² IV over 90 minutes (Day 1) * 5-FU: 2400 mg/m² IV over 48 hours infusion (Days 1) * Targeted Therapy: Administered according to NRAS/KRAS status and the location of the primary tumor: * KRAS/NRAS/BRAF Wild-Type (Left-Sided Tumor): Anti-EGFR treatment with either Panitumumab (6 mg/kg over 60 minutes, Day 1) or Cetuximab (500 mg/m², Day 1). * KRAS/NRAS Mutant or Right-Sided Tumor: Bevacizumab at a dose of 5 mg/kg IV over 30 to 90 minutes (Day 1). * Treatment Schedule: The treatment will be administered biweekly for a maximum of 12 cycles (6 months).

Drug: FOLFOXIRI Protocol

Interventions

FOLFOXIRI Protocol DRUG

as mentioned in Arm description

Also known as: Panitumumab, Bevacizumab, Cetuximab, modified FOLFOXIRI

modified FOLFOXIRI plus target therapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed unrespectable or metastatic colorectal cancer with or without primary tumor in situ.
• Patients were required to have measurable disease according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) (Eisenhauer EA,2009)
• ECOG PS 0-1 better to exclude PS II as this protocol is known to be toxic
• Adequate baseline hematology and clinical chemistry labs
• Adequate cardiac function

You may not qualify if:

• Double Malignancy
• DPYD mutant patients
• Peripheral neuropathy grade 3 or higher patient due to other comorbidities
• Inflammatory bowel syndrome or any other chronic GIT disease
• Prior exposure to chemotherapy treatment for colorectal cancer in the metastatic setting
• Patients who have contraindications for one or more of the study protocol drugs

Sponsors & Collaborators

• Al-Azhar University: lead

Study Sites (1)

Al Hussien University Hospital

Cairo, Cairo Governorate, 11311, Egypt

RECRUITING

Related Publications (14)

• Kalyan A, Kircher S, Shah H, Mulcahy M, Benson A. Updates on immunotherapy for colorectal cancer. J Gastrointest Oncol. 2018 Feb;9(1):160-169. doi: 10.21037/jgo.2018.01.17.

  PMID: 29564182 BACKGROUND

• 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 RESULT

• Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017 Apr;66(4):683-691. doi: 10.1136/gutjnl-2015-310912. Epub 2016 Jan 27.

  PMID: 26818619 RESULT

• Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000 Mar 25;355(9209):1041-7. doi: 10.1016/s0140-6736(00)02034-1.

  PMID: 10744089 RESULT

• Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001 Apr;48(4):526-35. doi: 10.1136/gut.48.4.526.

  PMID: 11247898 RESULT

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 RESULT

• Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. doi: 10.1200/JCO.2006.09.0928.

  PMID: 17470860 RESULT

• Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6:479-507. doi: 10.1146/annurev-pathol-011110-130235.

  PMID: 21090969 RESULT

• Folprecht G, Grothey A, Alberts S, Raab HR, Kohne CH. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol. 2005 Aug;16(8):1311-9. doi: 10.1093/annonc/mdi246. Epub 2005 May 3.

  PMID: 15870084 RESULT

• Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. doi: 10.1200/JCO.2006.06.9039.

  PMID: 16943526 RESULT

• Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.

  PMID: 15175435 RESULT

• Loupakis F, Cremolini C, Salvatore L, Masi G, Sensi E, Schirripa M, Michelucci A, Pfanner E, Brunetti I, Lupi C, Antoniotti C, Bergamo F, Lonardi S, Zagonel V, Simi P, Fontanini G, Falcone A. FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur J Cancer. 2014 Jan;50(1):57-63. doi: 10.1016/j.ejca.2013.08.024. Epub 2013 Oct 15.

  PMID: 24138831 RESULT

• Engstrom PF, Arnoletti JP, Benson AB 3rd, Chen YJ, Choti MA, Cooper HS, Covey A, Dilawari RA, Early DS, Enzinger PC, Fakih MG, Fleshman J Jr, Fuchs C, Grem JL, Kiel K, Knol JA, Leong LA, Lin E, Mulcahy MF, Rao S, Ryan DP, Saltz L, Shibata D, Skibber JM, Sofocleous C, Thomas J, Venook AP, Willett C; National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: colon cancer. J Natl Compr Canc Netw. 2009 Sep;7(8):778-831. doi: 10.6004/jnccn.2009.0056. No abstract available.

  PMID: 19755046 RESULT

• Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. doi: 10.1056/NEJMoa0805019.

  PMID: 19339720 RESULT

Related Links

• CTC V5

MeSH Terms

Conditions

Neoplasms; Colonic Neoplasms

Interventions

FOLFOXIRI protocol; Panitumumab; Bevacizumab; Cetuximab

Condition Hierarchy (Ancestors)

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

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: Specialist of Oncology

Model Details: Phase II single arm study

Study Record Dates

• First Submitted: August 25, 2024
• First Posted: August 28, 2024
• Study Start: August 17, 2024
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 28, 2024

Record last verified: 2024-08

Locations

EG (1)