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: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study involves standard combination chemotherapy treatment for colon cancer, 5-Fluorouracil (5FU), leucovorin and irinotecan (known as FOLFIRI), plus bevacizumab (Avastin). The study is designed to test the FOLFIRI regimen based on certain characteristics of a person's genetic makeup or "genes". Genes are made of DNA and determine not only inherited traits or appearance (hair and eye color, height, body type, etc.) but also play an important role in health and how the body responds to illness and treatments for those illnesses. In this study, the investigators will examine the relationship between a patient's genes (DNA), or "genotype", and how the patient's body breaks down and removes or "metabolizes" the anti-cancer drug irinotecan. Circulating blood level of irinotecan plays an important role in how well this drug works against a patient's cancer as well as the adverse side effects the patient may experience. The current standard dose of irinotecan was determined in clinical trials without knowing individual genotypes and thus does not take into account a patient's ability to metabolize irinotecan. This means that based on one genotype the current standard dose of irinotecan may be correct or based on other genotypes the standard dose could result in lower and possibly less effective blood levels and result in significant under-dosing of irinotecan. Based on genotype the patient will be assigned to one of the following doses of irinotecan: * 180 mg/m2 (standard dose) * 260 mg/m2 * 310 mg/m2 The purpose of this research study is to determine if dosing irinotecan based on genotype is effective and safe for patients with colon cancer. Patient genotype will be determined from a small sample of blood and a laboratory test or "assay" performed at UNC Laboratories. For the purpose of this study, this assay is new and considered to be "investigational". This means that the genotype assay used in this study has not yet been approved by the FDA for determining irinotecan dose levels in patients with colon cancer.

Research Team

Hanna Sannoff, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

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+