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Neoplasm MalignantPhase 2NCT06575127

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

A Phase 2 study testing FOLFOXIRI Protocol in people with Neoplasm Malignant and Colon Cancer Stage 4, run by Al-Azhar University at 1 site in Egypt.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. . Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Neoplasm Malignant, Colon Cancer Stage 4
What is being tested?
FOLFOXIRI Protocol
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteEgypt
Study dates
17 Aug 2024to 1 Sep 2026
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Egypt1 site, 1 recruiting

  • Al Hussien University Hospital

    Cairo, Cairo Governorate, 11311

    Mohamed Soliman, +2025063560, mohamed.abdelaziz077@gmail.com

    Mohamed A Abdelaziz

    Recruiting

Other trials in Egypt

About this study

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.

Read the detailed description

This prospective Phase II clinical trial aims to assess the efficacy and safety of a modified dose regimen of FOLFOXIRI in the treatment of metastatic colorectal cancer (MCRC). FOLFOXIRI is a chemotherapy regimen known for its high toxicity, necessitating close monitoring, dose reductions, and supportive treatments. While previous studies have demonstrated the clinical efficacy of FOLFOXIRI compared to FOLIRI or FOLFOX, the regimen's toxicity remains a significant concern.

Intervention:

Modified FOLFOXIRI Regimen:

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 (Day 1)

Targeted Therapy:

KRAS/NRAS/BRAF Wild-Type (Left-Sided Tumor): Anti-EGFR treatment with either Panitumumab (6 mg/kg IV over 60 minutes, Day 1) or Cetuximab (500 mg/m² IV, Day 1).

KRAS/NRAS Mutant or Right-Sided Tumor: Bevacizumab (5 mg/kg IV over 30-90 minutes, Day 1).

Treatment Schedule: Administered biweekly for a maximum of 12 cycles (6 months).

G-CSF Prophylaxis: Administered as primary prophylaxis for patients older than 55 and as secondary prophylaxis for those who develop grade ≥3 neutropenia.

Dose Modifications and Treatment-Related Toxicity:

Toxicity will be evaluated after each cycle using the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 (National Cancer Institute, 2017).

Dose Reduction Guidelines: A 25% dose reduction will be implemented for specific grade III/IV acute toxicities including neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, mucositis/stomatitis, hand-foot syndrome, peripheral neuropathy, elevated liver enzymes, severe fatigue, hypertension, proteinuria, and dermatologic toxicity.

Treatment Discontinuation: Patients who experience further grade III/IV acute toxicity after dose reduction will be excluded from the study.

Treatment Duration:

Eligible for Surgery: Patients with a favorable response will receive a maximum of 8 cycles before surgical evaluation.

Ineligible for Surgery: Treatment will continue until the completion of 12 cycles, intolerable toxicity, or a maximum duration of 6 months.

Assessments:

Disease Assessment: Performed every 4 cycles (8 weeks) during the induction phase, followed by every 3 months. Quality of life will be evaluated using the EORTC QLQ C30 and CR 29 questionnaires.

Response Assessment: Based on RECIST v1.1 criteria, categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD).

Statistical Analysis:

Survival Analysis: Kaplan-Meier estimates with one-sided log-rank tests will be used to analyze progression-free survival (PFS). Overall survival (OS) will be calculated from the date of histological diagnosis to the date of last follow-up or death.

Data Analysis: Data will be analyzed using IBM SPSS version 26. Quantitative data will be presented as means, standard deviations, and ranges, or as medians with interquartile ranges, depending on distribution. Qualitative data will be presented as frequencies and percentages. Chi-square tests will compare groups with qualitative data. The confidence interval is set at 95%, with a significance threshold of p < 0.05.

Being tested
FOLFOXIRI Protocol
Keywords
Colon Cancer, MCRC, FOLFOXIRI
Medical subject headings
Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFOXIRI ProtocolDrug

    Also called Panitumumab, Bevacizumab, Cetuximab, modified FOLFOXIRI

    as mentioned in Arm description

Study groups in NCT06575127
Study groupRoleWhat they receive
modified FOLFOXIRI plus target therapyExperimental* 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).
Receives: Drug: FOLFOXIRI Protocol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment-related adverse events

    evaluate treatment-related acute and delayed toxicity

    Measured: 12 months

  2. Objective Response Rate

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

    Measured: 6 months

Secondary outcomes (3)

  1. Conversion therapy

    To assess the treatment's efficacy as a conversion therapy, transforming initially unresectable tumors to resectable ones, response rates will be evaluated every 4 treatment cycles according to RECIST v1.1 (Eisenhauer EA, 2009):

    Complete Response (CR): Disappearance of all lesions and pathological lymph nodes.

    Partial Response (PR): ≥30% decrease in the sum of the longest diameters (SLD) of target lesions, no new lesions, and no progression in non-target lesions.

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Progressive Disease (PD): ≥20% increase in SLD or the appearance of new lesions.

    Patients eligible for surgery may receive up to 8 cycles before surgical evaluation. Those showing favorable response will be referred for potential surgical intervention.

    Measured: 4 months

  2. Progression free survival

    to study the impact of treatment on progression free survival

    Measured: 12 months

  3. Overall survival

    to study the impact of treatment on 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.

  1. First posted28 Aug 2024
  2. Study start17 Aug 2024
  3. Primary completion1 Sep 2025 (estimated)
  4. Study completion1 Sep 2026 (estimated)

Resources

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
Phase II single arm study
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06575127
Sponsor's protocol ID
FOXIRI
Status last verified
Aug 2024
First submitted
25 Aug 2024
Last updated
28 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: study protocol and statistical analysis will be shared

Publications

  • 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.

    PubMed 29564182

  • 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.

    PubMed 18316791

  • 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.

    PubMed 26818619

  • 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.

    PubMed 10744089

  • 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.

    PubMed 11247898

  • 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.

    PubMed 19097774

  • 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.

    PubMed 17470860

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

    PubMed 21090969

  • 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.

    PubMed 15870084

  • 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.

    PubMed 16943526

  • 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.

    PubMed 15175435

  • 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.

    PubMed 24138831

  • 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.

    PubMed 19755046

  • 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.

    PubMed 19339720

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FOLFOXIRI Protocol in people with Neoplasm Malignant and Colon Cancer Stage 4, run by Al-Azhar University at 1 site in Egypt.

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 5 inclusion and 6 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 28 Aug 2024. 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 Egypt. 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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment-related adverse events (time frame: 12 months). The study lists 2 primary outcomes in all. 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 NCT06575127, which also lists 14 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 28 Aug 2024.

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