Genotype-Directed Chemotherapy for Colorectal Cancer

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Prohibited drugs

Disqualifiers: Hypertension, Cardiac disease, Bleeding disorders, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 8 years

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment plan for colon cancer using a combination of chemotherapy drugs. Researchers aim to determine if adjusting the dose of irinotecan (Camptosar or CPT-11) based on a person's genes can enhance treatment effectiveness and safety. The study includes a blood test to assess how a person's body processes the drug, which may help determine the optimal dose. Individuals with colon cancer who have not received chemotherapy for their metastatic disease might be suitable candidates for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that irinotecan, a key component of the FOLFIRI chemotherapy regimen, is both effective and challenging regarding safety. In studies with colorectal cancer patients, irinotecan successfully treated the disease. However, this drug can cause serious side effects that require careful monitoring.

One study involved 955 patients with advanced colorectal cancer who received irinotecan with other chemotherapy drugs. This combination posed risks, including severe side effects. These side effects can sometimes be so intense that they lead to delays or pauses in treatment.

Irinotecan is commonly used in cancer treatment, but it requires ongoing safety checks due to these known risks. This ensures that any negative reactions are quickly addressed to prevent complications.

Overall, while irinotecan has effectively combated cancer, its safety profile is complex. Patients in trials should be aware of these risks and discuss any concerns with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about these treatments because they are tailored to the patient's genetic makeup. Unlike the standard chemotherapy options that use a one-size-fits-all approach, this trial uses genotype-directed dosing of irinotecan for colorectal cancer. By doing so, it aims to optimize the effectiveness and minimize the side effects of chemotherapy. This personalized approach could potentially lead to better outcomes compared to traditional treatments.

What evidence suggests that genotype-directed dosing of irinotecan could be effective for colon cancer?

Research has shown that using irinotecan with other drugs like 5-fluorouracil and leucovorin can help treat colorectal cancer. Studies have found that adding irinotecan can increase the one-year survival rate by 40% for patients with metastatic colorectal cancer compared to those who don't receive it. Specifically, one study showed that a treatment plan including irinotecan led to positive outcomes, with patients experiencing over 13 months without cancer progression and a 79.4% overall response rate. This indicates that irinotecan can play a crucial role in shrinking the cancer or keeping it under control. However, the effectiveness of irinotecan can depend on how a person's body processes the drug, which is influenced by their genes. This trial will explore whether adjusting the dose based on genetics can lead to better results, with different treatment arms for the *1/*1, *1/*28, and *28/*28 genotypes. ^{2 6 7 8 9}

Who Is on the Research Team?

Hanna Sannoff, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with measurable metastatic colorectal cancer who haven't had chemotherapy for it yet. They must be in fairly good health, willing to have their UGT1A1 gene tested, and able to use effective birth control. People can't join if they have certain heart conditions, uncontrolled high blood pressure, severe proteinuria, recent major surgeries or injuries, a history of significant bleeding disorders or stroke within the past 6 months.

Inclusion Criteria

My cancer has spread and cannot be removed by surgery to cure it.

serum creatinine ≤1.5 x upper limit of normal (ULN)

Bilirubin ≤1.5 X ULN

Exclusion Criteria

I can stop taking certain medications and avoid specific fruits for the required time before starting my treatment.

I have had hypertensive encephalopathy in the past.

My urine tests show significant protein levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genotyping and Treatment Assignment

Participants are genotyped for UGT1A1 and assigned to one of three dosing groups based on their genotype.

1 week

Treatment

Participants receive FOLFIRI plus bevacizumab with irinotecan dosing based on genotype. Treatment cycles repeat every 28 days.

Up to 8 years

IV administration on Day 1 and Day 15 of each cycle

Follow-up

Participants are monitored for progression-free survival and adverse events.

Up to 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan

Trial Overview The trial is testing different doses of irinotecan (180 mg/m2, 260 mg/m2, or 310 mg/m2) combined with standard chemo drugs (5FU and leucovorin) plus bevacizumab for colon cancer treatment. The dose depends on the patient's genotype which affects how well they process the drug. This could make treatment more effective and safer.

How Is the Trial Designed?

Group I: *28/*28 Experimental Treatment 4 Interventions

FOLFIRI (5-fluorouracil (5-FU), leucovorin, irinotecan) Irinotecan dose 180 mg/m2, FOLFIRI (IV, Day 1, 15); Bevacizumab (IV, Day 1, 15), repeat treatment cycle every 28 days.

Group II: *1/*28 Genotype Experimental Treatment 4 Interventions

FOLFIRI (5-fluorouracil (5-FU), leucovorin, irinotecan) Irinotecan dose 260 mg/m2, FOLFIRI (IV, Day 1, 15); Bevacizumab (IV, Day 1, 15), repeat treatment cycle every 28 days.

Group III: *1/*1 Genotype Experimental Treatment 4 Interventions

FOLFIRI (5-fluorouracil (5-FU), leucovorin, irinotecan) Irinotecan dose 310 mg/m2,(IV, Day 1, 15); Bevacizumab (IV, Day 1, 15), repeat treatment cycle every 28 days.

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

University Cancer Research Fund

Collaborator

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9575722/

The efficacy of irinotecan supplementation for colorectal ... This meta-analysis aims to assess the efficacy and safety of irinotecan in combination with fluorouracil and leucovorin for colorectal cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/0959804995002122

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- ...

3. cancernetwork.com cancernetwork.com/view/irinotecan-may-extend-survival-people-metastatic-colorectal-cancer

Irinotecan May Extend Survival in People With Metastatic ... Researchers demonstrated that at 1 year, the overall survival rate of metastatic colorectal cancer patients who received irinotecan was 40% higher than that of ...

4. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1356708/full

The effective combination therapies with irinotecan for ... The FOLFOXIRI regimen showed promising outcomes with a PFS of 13.37 ± 9 months, an overall response rate of 79.4%, a significant decrease in the risk of early ...

5. esmoopen.com esmoopen.com/article/S2059-7029(25)00160-7/fulltext

effectiveness results from the CIREL study Irinotecan-TACE can thus be potentially used either as a salvage therapy to achieve tumour control or as a post-inductive/consolidation therapy ...

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

Safety evaluation of irinotecan - PubMed Central Despite its therapeutic efficacy, the safety profile of irinotecan necessitates continuous pharmacovigilance due to its association with severe adverse drug ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/020571s048lbl.pdf

CAMPTOSAR (Irinotecan) Injection, intravenous infusion A total of 955 patients with metastatic colorectal cancer received the recommended regimens of irinotecan in combination with 5-FU/LV, 5-FU/LV alone, or ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1347861319310424

Prediction of irinotecan toxicity in metastatic colorectal ... Irinotecan (CPT-11) is a drug used against a wide variety of tumors, which can cause severe toxicity, possibly leading to the delay or suspension of the ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2794679/

Generalizability of toxicity data from oncology clinical trials ... Overall, the toxicity rates for folfiri and irinotecan monotherapy in non-trial patients were not statistically different from the rates quoted in published ...