Chemotherapy Combinations for Colon Cancer

(IROCAS Trial)

No longer recruiting at 19 trial locations

Overseen By Beata JUZYNA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: UNICANCER

Disqualifiers: Metastatic disease, Inflammatory bowel disease, Coronary artery disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 13

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two combinations of chemotherapy drugs to determine which is more effective for treating high-risk stage III colon cancer after surgery. Patients will receive either a treatment that includes irinotecan (Camptosar or CPT-11) with other drugs or another combination without irinotecan. The goal is to compare the effectiveness of these treatments in preventing cancer recurrence. Individuals who have undergone surgery for high-risk stage III colon cancer and have not received prior chemotherapy might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients an opportunity to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since no prior chemotherapy is allowed, you may need to discuss your current medications with the trial team to ensure they don't interfere with the study treatments.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that irinotecan is usually well-tolerated, but it can cause serious side effects. Most patients handle higher doses, though some may require hospitalization. In contrast, oxaliplatin, often used with other drugs, has not shown unexpected side effects in safety studies. While some patients experience severe side effects, these are not common enough to be a major concern. Both irinotecan and oxaliplatin play important roles in treating colorectal cancer and have undergone thorough safety studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these chemotherapy combinations for colon cancer because they aim to improve treatment effectiveness by using different drug protocols. Arm A combines mFOLFIRINOX with Irinotecan, a combination that could enhance the potency of the treatment by intensifying the attack on cancer cells. This blend might offer a more aggressive approach compared to the standard mFOLFOX 6 regimen used in Arm B. The hope is that these combinations can lead to better outcomes by leveraging the distinct mechanisms of action of Irinotecan and Oxaliplatin, potentially improving survival rates or reducing side effects for patients.

What evidence suggests that this trial's chemotherapy combinations could be effective for colon cancer?

Research has shown that using irinotecan with fluorouracil can help patients with metastatic colorectal cancer live longer without their cancer worsening. In this trial, participants in Arm A will receive a combination that includes irinotecan, which is effective when other treatments fail. Meanwhile, Arm B will involve a regimen that includes oxaliplatin. Adding oxaliplatin to other drugs also improves outcomes for people with metastatic colorectal cancer. It is commonly used in treating stage III colon cancer and has been shown to increase survival rates. Both irinotecan and oxaliplatin play crucial roles in treating advanced colon cancer, with strong evidence supporting their effectiveness. ^{4 6 7 8 9}

Who Is on the Research Team?

Jaafar BENNOUNA, Professor

Principal Investigator

Hôpital FOCH, SURESNES

Julien TAIEB, Professor

Principal Investigator

Hôpital Européen Georges-Pompidou, PARIS

Thierry ANDRE, Professor

Principal Investigator

AP-HP Hôpital Saint-Antoine, PARIS

Are You a Good Fit for This Trial?

Adults aged 18-75 with high-risk stage III colon cancer who've had surgery for it, have good organ function, and no prior chemo or radiation. They must not have other significant diseases, a history of certain cancers within the last 5 years, or be in another drug trial. Pregnant women and those with central nervous system disease or peripheral neuropathy are excluded.

Inclusion Criteria

I have not had radiation therapy to my abdomen or pelvis.

Adequate organ function including ANC ≥ 2 x 109/L, Haemoglobin ≥9 g/dL, Platelets (PTL) ≥100 x 109/L, AST/ALT ≤2.5 x ULN, Alkaline phosphatase ≤2.5 x ULN, Total Bilirubin ≤1.5 x ULN, Creatinine clearance ≥50 mL/min, Kalemia, magnesemia, calcemia ≥ 1 LLN, CEA ≤10ng/mL after surgery, Adequate contraception if applicable, Able and willing to comply with study procedures, Able to understand and sign informed consent form, Public or private health insurance coverage, Life expectancy of > or = 5 years, Uracilemia < 16 ng/ml (only for French centers)

My colon cancer is at a high-risk stage III.

Exclusion Criteria

I haven't had major surgery or a serious injury in the last 28 days.

I have no or mild nerve damage or brain-related health issues.

Pregnancy or breast-feeding period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive mFOLFIRINOX or mFOLFOX 6 chemotherapy every 14 days for 12 cycles

24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Regular visits (frequency not specified)

Long-term follow-up

Participants are monitored for overall survival and disease-free survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan
• Oxaliplatin

Trial Overview

The study compares two chemotherapy protocols for colon cancer after surgery: mFOLFIRINOX (a mix of irinotecan, oxaliplatin, folinic acid & fluorouracil) versus mFOLFOX6 (oxaliplatin with folinic acid & fluorouracil). It's to see which is better at preventing cancer from coming back.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

mFOLFIRINOX Folfox Protocol + Irinotecan

Group II: Arm B Active Control 1 Intervention

mFOLFOX 6 Folfox Protocol

Irinotecan is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Camptosar for:

• Colorectal cancer

Approved in European Union as Irinotecan for:

• Colorectal cancer

Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

Approved in Canada as Irinotecan for:

• Colorectal cancer

Who Is Running the Clinical Trial?

UNICANCER

Lead Sponsor

Trials

237

Recruited

352,000+

GONO GROUP

Collaborator

Trials

1

Recruited

790+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Published Research Related to This Trial

In a randomized phase II trial involving 80 patients with advanced colorectal cancer, the combination of irinotecan and oxaliplatin (IRINOX) showed a 52.5% partial response rate with a median duration of 7.2 months, indicating its efficacy as a first-line treatment.

The IRINOX regimen had manageable toxicity levels, with significant side effects including neutropenia and diarrhea, but overall survival times were comparable to the standard treatment arm, suggesting it is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer. Bécouarn, Y., Senesse, P., Thézenas, S., et al.[2020]

Irinotecan (CPT-11) demonstrated efficacy in treating advanced colorectal cancer, achieving an overall response rate of 18% in a study of 213 patients, including both chemotherapy-naive and pretreated individuals.

The treatment was associated with manageable adverse effects, primarily neutropenia and delayed diarrhea, with severe side effects occurring in a minority of treatment cycles, indicating that while CPT-11 is effective, careful monitoring for these toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy. Rougier, P., Bugat, R., Douillard, JY., et al.[2018]

Irinotecan is an approved treatment for colorectal cancer that does not respond to fluorouracil, highlighting its role in managing difficult cases of this disease.

The review addresses the drug's toxicity and management strategies, indicating that while irinotecan is effective, careful monitoring and handling of side effects are crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Use of Irinotecan: Current Status and Future Considerations. Saltz, LB.[2019]

In a phase I trial involving 23 patients with metastatic or recurrent colorectal cancer, the recommended doses for S-1 and irinotecan (CPT-11) were established at 80 mg/m² and 225 mg/m², respectively, with manageable dose-limiting toxicities including grade 3 ileus and diarrhea.

The combination treatment showed promising efficacy, with an objective response rate of 41% in patients with measurable disease, indicating that further phase II trials are justified to explore this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of combination therapy with S-1 and irinotecan in patients with previously untreated metastatic or recurrent colorectal cancer. Choi, YH., Kim, TW., Lee, SS., et al.[2018]

In a study of 16 patients with 5-fluorouracil-resistant metastatic colorectal cancer, irinotecan (CPT-11) demonstrated a partial response rate of 6.3% and a high rate of stable disease (43.7%), indicating its efficacy in this challenging patient population.

The median survival time for patients treated with CPT-11 was 69.6 weeks, with no toxic deaths reported, suggesting that CPT-11 is a safe and beneficial treatment option for patients resistant to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity and benefit of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma pre-treated with fluorouracil-based chemotherapy. Ratanatharathorn, V., Sirachainan, E., Jirajarus, M., et al.[2018]

Irinotecan has shown significant activity against advanced colorectal cancer when combined with traditional chemotherapy agents like fluorouracil, leading to clinical responses including complete remissions in patients.

The combination therapies have acceptable toxicity profiles, with neutropenia and delayed diarrhea being the most common side effects, indicating that irinotecan could be a safe option for treatment, although further large-scale phase III studies are needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. Khayat, D., Gil-Delgado, M., Antoine, EC., et al.[2018]

Combining irinotecan hydrochloride (SN-38) with cisplatin significantly enhances the anticancer effects against colorectal cancer, as shown by a study using freshly isolated cancer cells from 20 patients.

The study found that even at lower concentrations, the combination of SN-38 and cisplatin produced a strong synergistic effect, suggesting a promising strategy for improving chemotherapy outcomes in advanced colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. Tsunoda, T., Tanimura, H., Hotta, T., et al.[2019]

Xiao-Chai-Hu-Tang (XCHT) effectively alleviates irinotecan (CPT-11)-induced diarrhea by reducing inflammation and improving the abundance of beneficial gut bacteria, as shown in a study with treated mice.

The active ingredient baicalein from XCHT selectively inhibits β-glucuronidase (β-GUS), a key enzyme linked to diarrhea caused by CPT-11, suggesting it could be a promising candidate for managing this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut β-GUS. Wang, C., Teng, X., Wang, C., et al.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

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sciencedirect.com

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effectiveness results from the CIREL study

The median OS (95% CI) of irinotecan-TACE as salvage therapy was 9.9 months (7.4-12.8 months) and the median PFS was 3.8 months (2.9-4.7 months) ...

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pubmed.ncbi.nlm.nih.gov

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CPT-11 (irinotecan) in the treatment of colorectal cancer

Although 50% of patients are cured by surgery alone, the outcome is poor in high-risk patients (Dukes stages B2 and C) despite adjuvant chemotherapy with 5- ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S113063432300137X

Efficacy and safety of high doses of irinotecan in patients ...

Irinotecan safety studies suggest that doses higher than 180 mg/m 2 are tolerated by most UGT1A1*1/*1 and *1/*28 patients.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12184384/

Safety evaluation of irinotecan - PubMed Central

In terms of outcomes, other serious outcomes (37.9%), hospitalizations (29.6%), and deaths (19.0%) accounted for the largest proportion of reported events in ...

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A single-center retrospective analysis of the efficacy and ...

Second-line treatment with the modified IRIS regimen (irinotecan 85 mg/m 2 ) is associated with good PFS and OS and causes few serious adverse events.