Novel Interventions for Colorectal Cancer

(CANTOR Trial)

Recruiting at 49 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Disqualifiers: CNS metastases, Autoimmune disorders, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 3 years

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to evaluate the safety and efficacy of novel study interventions and combinations in participants with Colorectal Cancer (CRC).

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Bevacizumab, FOLFIRI, and Volrustomig for colorectal cancer?

Research shows that combining Bevacizumab with chemotherapy regimens like FOLFIRI (a mix of cancer-fighting drugs) can improve treatment outcomes for advanced colorectal cancer. Studies have found that adding Bevacizumab to these regimens increases their effectiveness in treating this type of cancer. ^{1 2 3 4 5}

What safety data exists for treatments like Bevacizumab and FOLFIRI in humans?

Bevacizumab-based treatments can lower the risk of skin and kidney issues but may increase the risk of heart-related problems like high blood pressure and irregular heartbeat. It can also cause bleeding when combined with certain chemotherapy drugs. ^{2 6 7 8 9}

What makes the drug combination of Bevacizumab, FOLFIRI, and Volrustomig unique for treating colorectal cancer?

This treatment is unique because it combines Bevacizumab, which inhibits blood vessel growth in tumors, with FOLFIRI, a chemotherapy regimen, and Volrustomig, a novel component not commonly used in standard treatments, potentially offering a new approach to managing colorectal cancer. ^{3 10 11 12 13}

Eligibility Criteria

This trial is for adults with confirmed colorectal cancer, good performance status (able to carry out daily activities), expected to live at least 12 weeks, no liver metastasis, and haven't had systemic therapy for metastatic CRC. They must have a specific tumor type (pMMR/MSS), be over 35 kg in weight, and have measurable disease.

Inclusion Criteria

My doctor expects me to live for at least 12 more weeks.

My diagnosis is colorectal adenocarcinoma confirmed by tissue analysis.

I can provide a tumor sample that was collected according to standard procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either Volrustomig + FOLFIRI + bevacizumab or FOLFIRI + bevacizumab

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Bevacizumab
• FOLFIRI
• Volrustomig

Trial Overview The study tests the safety and effectiveness of new treatments and combinations in colorectal cancer patients. It includes Bevacizumab, Volrustomig, and FOLFIRI regimen which consists of Fluorouracil (5-FU), leucovorin, and irinotecan.

Participant Groups

Group I: Volrustomig + FOLFIRI+ Bevacizumab group (Arm A) Experimental Treatment 3 Interventions

Participants will receive FOLFIRI and bevacizumab together with volrustomig.

Group II: FOLFIRI+ BEVACIZUMAB group (Arm B) Active Control 2 Interventions

Partcipants will receive FOLFIRI and bevacizumab.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

The combination of FOLFOXIRI and bevacizumab demonstrated a promising progression-free survival (PFS) rate of 74% at 10 months in patients with unresectable metastatic colorectal cancer, based on a phase 2 study involving 57 patients.

The treatment was found to be safe, with no unexpected adverse events reported, although common serious side effects included neutropenia and hypertension, indicating that while effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Masi, G., Loupakis, F., Salvatore, L., et al.[2022]

In a study of 14 patients with advanced colorectal cancer who had previously undergone chemotherapy, the combination of bevacizumab with FOLFIRI showed a response rate of 28.5%, with one complete response and three partial responses, indicating its potential efficacy in this heavily treated population.

The treatment was generally well tolerated, with manageable side effects; serious complications like hypertension, bowel perforation, or thromboembolic events were not observed, suggesting a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy: a pilot study. Kwon, HC., Oh, SY., Lee, S., et al.[2022]

In a study involving 84 patients with advanced colorectal cancer, the FOLFOX4 regimen showed a significantly higher overall response rate (ORR) of 40.5% compared to 9.5% for the FFG regimen, indicating greater efficacy for FOLFOX4.

While both treatment regimens were generally well tolerated, FOLFOX4 was associated with a higher incidence of peripheral neuropathy (42.9%) compared to FFG (2.4%), highlighting a safety concern with the FOLFOX4 regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, randomized phase II trial of bevacizumab plus folinic acid, fluorouracil, gemcitabine (FFG) versus bevacizumab plus folinic acid, fluorouracil, oxaliplatin (FOLFOX4) as first-line therapy for patients with advanced colorectal cancer. Madajewicz, S., Waterhouse, DM., Ritch, PS., et al.[2021]

In patients with unresectable RAS wild-type metastatic colorectal cancer, first-line bevacizumab-based chemotherapy significantly reduces the risk of dermatological and renal adverse events, but increases the risk of cardiovascular issues like hypertension and arrhythmia.

Conversely, cetuximab-based chemotherapy is associated with a higher incidence of dermatological and renal adverse events, particularly rashes and electrolyte disorders, highlighting the need for careful selection of targeted therapies based on safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability on Serious Adverse Events of First-Line Bevacizumab and Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Han, YN., Choi, YJ., Rhie, SJ.[2022]

In a meta-analysis of 11 randomized controlled trials involving 3178 patients, the combination of bevacizumab (BEV) with the FOLFOX regimen significantly improved the objective response rate and cancer control rate compared to FOLFOX alone.

However, this combination treatment was associated with a higher incidence of gastrointestinal adverse reactions, indicating a trade-off between increased efficacy and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of bevacizumab combined with FOLFOX regimen in the treatment of advanced colorectal cancer: A systematic review and meta-analysis. Zhang, H., You, J., Liu, W., et al.[2023]

In a study of 60 metastatic colorectal cancer patients treated with bevacizumab and chemotherapy, the most common side effects were mild bleeding (28%) and hypertension (17%), indicating that while there are some toxicities, they are generally manageable.

Serious complications were rare, with only 5% of patients experiencing severe venous thromboembolic events and gastrointestinal perforation, suggesting that bevacizumab is well tolerated in combination with various chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of first-line bevacizumab in metastatic colorectal cancer. Akun, E., Okutur, K., Seber, S., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab in association with de Gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of FOLFOXIRI plus molecular target drug therapy for metastatic colorectal cancer: A multicenter retrospective study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy: a pilot study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Multicenter, randomized phase II trial of bevacizumab plus folinic acid, fluorouracil, gemcitabine (FFG) versus bevacizumab plus folinic acid, fluorouracil, oxaliplatin (FOLFOX4) as first-line therapy for patients with advanced colorectal cancer. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tolerability on Serious Adverse Events of First-Line Bevacizumab and Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The efficacy and safety of bevacizumab combined with FOLFOX regimen in the treatment of advanced colorectal cancer: A systematic review and meta-analysis. [2023]

8. Cyprus pubmed.ncbi.nlm.nih.gov

Safety and tolerability of first-line bevacizumab in metastatic colorectal cancer. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Bleeding after bevacizumab treatment in patients with metastatic colorectal cancer. [2018]

10. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of bevacizumab plus capecitabine for metastatic colorectal cancer]. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Cetuximab versus bevacizumab maintenance following prior 8-cycle modified FOLFOXIRI plus cetuximab in Asian postmenopausal women with treatment-naive KRAS and BRAF wild-type metastatic colorectal cancer. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

The efficacy and safety of adding bevacizumab to cetuximab- or panitumumab-based therapy in the treatment of patients with metastatic colorectal cancer (mCRC): a meta-analysis from randomized control trials. [2023]