Chemotherapy Combinations for Colon Cancer

(IROCAS Trial)

Recruiting at 16 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

792 Participants Needed

Trial Summary

What is the purpose of this trial?

The trial is a phase III, multicenter, open-labeled randomized trial comparing the association of 5-fluorouracil (5-FU), folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) versus oxaliplatin, folinic acid, and 5-FU (mFOLFOX 6) chemotherapy protocols in patients with high-risk stage III colon cancer in the adjuvant setting.

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.

What data supports the effectiveness of the drug combination of Irinotecan and Oxaliplatin for colon cancer?

Research shows that the combination of Irinotecan and Oxaliplatin is effective as a first-line treatment for advanced colorectal cancer, with studies indicating that these drugs work well together to fight the cancer. ^{1 2 3 4 5}

Is the chemotherapy combination of Irinotecan and Oxaliplatin safe for humans?

Studies have shown that the combination of Irinotecan (also known as CPT-11 or Camptosar) and Oxaliplatin (Eloxatin) has been evaluated for safety in patients with advanced gastrointestinal cancers. However, Irinotecan can cause side effects like diarrhea, which can limit its use. ^{6 7 8 9 10}

What makes the chemotherapy drug combination of Irinotecan and Oxaliplatin unique for colon cancer?

The combination of Irinotecan and Oxaliplatin is unique because it combines two powerful drugs that have shown strong antitumor effects against colorectal cancer, and it is often used when other treatments have failed. This combination is part of a triplet therapy with continuous-infusion fluorouracil and leucovorin, which has been evaluated as a first-line treatment for metastatic colorectal cancer, offering a novel approach compared to traditional therapies. ^{2 11 12 13 14}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. England 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. [2020]

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

Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial. [2018]

3. United States 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. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Second-Line Treatment of Advanced Colorectal Cancer with a Biweekly Oxaliplatin plus Irinotecan Combination Regimen. [2018]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of combination of irinotecan and capecitabine in patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin]. [2018]

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

Combination of oxaliplatin plus irinotecan in patients with gastrointestinal tumors: results of two independent phase I studies with pharmacokinetics. [2018]

7. Germany 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. [2023]

8. Germany 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. [2018]

9. England pubmed.ncbi.nlm.nih.gov

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

10. Thailand 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. [2018]

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

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. [2018]

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

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. [2019]

13. Germany pubmed.ncbi.nlm.nih.gov

Clarithromycin co-administration does not increase irinotecan (CPT-11) toxicity in colorectal cancer patients. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Irinotecan (CPT11) plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) as salvage therapy for metastatic colorectal cancer (MCRC) after failed oxaliplatin plus 5-FU and LV: a pilot study in Taiwan. [2019]