Genotype-Directed Study Of Irinotecan Dosing In FOLFIRI + BevacizumabTreated Metastatic Colorectal Cancer

NCT02138617 | Completed Phase 2 Results DMC

• 1 other identifier: LCCC1317
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

Brief Summary

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 University of North Carolina 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.

Conditions

Colon Cancer

Keywords

Colon Cancer; Irinotecan; FOLFIRI; Genotyping; UGT1A1

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression-free Free Survival is defined as the time from day 1 (D1) of treatment to progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST)1.1 or death from any cause. Radiographic response will be measured by RECIST, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  From date of registration until date of first documented progression up to 8 years.

Secondary Outcomes (3)

• Number of Participants With Grade 3 or Higher Adverse Events

  From date of registration up to 8 years.

• Overall Response

  5 years

• Overall Survival Rate

  8 years

Study Arms (3)

*1/*1 Genotype

EXPERIMENTAL

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.

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Irinotecan; Drug: Bevacizumab

*1/*28 Genotype

EXPERIMENTAL

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.

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Irinotecan; Drug: Bevacizumab

*28/*28

EXPERIMENTAL

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.

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Irinotecan; Drug: Bevacizumab

Interventions

5-Fluorouracil DRUG

400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours, Day 1 and Day 15 .

Also known as: 5-FU, Adrucil

*1/*1 Genotype; *1/*28 Genotype; *28/*28

Leucovorin DRUG

200-400 mg/m2 IV over 2 hours, Day 1 and Day 15

Also known as: LV, leucovorin calcium, folinic acid, citrovorum factor

*1/*1 Genotype; *1/*28 Genotype; *28/*28

Irinotecan DRUG

IV infusion over 90 minutes, dosed at 180, 260 or 310 mg/m2 based on genotype.

Also known as: Camptosar, Novaplus Irinotecan Hydrochloride

*1/*1 Genotype; *1/*28 Genotype; *28/*28

Bevacizumab DRUG

Bevacizumab (5 mg/kg IV infused as per institutional policy, IV, Day 1, 15)

Also known as: Avastin, MVASI

*1/*1 Genotype; *1/*28 Genotype; *28/*28

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An Institutional Review Board-approved informed consent obtained and signed
• Age ≥ 18 years
• Histological or cytological documentation of adenocarcinoma of the colon or rectum
• Measurable or non-measurable (but evaluable) disease as defined via RECIST 1.1
• Metastatic disease not amenable to surgical resection with curative intent
• No prior chemotherapy for metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see section 11.1, Appendix A)
• Adequate bone marrow, renal and hepatic function, as evidenced by the following:
• absolute neutrophil count (ANC) ≥1,500/mm3
• platelets ≥100,000/mm3
• hemoglobin ≥9.0 g/dL
• serum creatinine ≤1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤3x ULN ( ≤5.0 × ULN for patients with liver involvement of their cancer
• Bilirubin ≤1.5 X ULN
• Alkaline phosphatase ≤3 x ULN (≤5 x ULN with liver involvement of their cancer)

You may not qualify if:

• UGT1A1 genotype other than \*1/\*1, \*1/\*28, or \*28/\*28
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Prior treatment with irinotecan and/or bevacizumab
• Unable or unwilling to discontinue (and substitute if necessary) use of prohibited drugs for at least 14 days (fruits and juices for at least 7 days) prior to Day 1 of FOLFIRI + bevacizumab initiation (see section 11.2, Appendix B, for list of prohibited drugs)
• Inadequately controlled hypertension (defined as systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90 mmHg)
• Prior history of hypertensive encephalopathy
• Active cardiac disease including any of the following:
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see section 11.3, Appendix C)
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1 of FOLFIRI + bevacizumab initiation
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of FOLFIRI + bevacizumab initiation
• History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 of FOLFIRI + bevacizumab initiation
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of FOLFIRI + bevacizumab initiation or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 of FOLFIRI + bevacizumab initiation

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• University Cancer Research Fund: collaborator

Study Sites (7)

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Arnett Hospital

Lafayette, Indiana, 47905, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Carolina Healthcare Systems

Charlotte, North Carolina, 28204, United States

Location

Cone Health Cancer Center

Greensboro, North Carolina, 27403, United States

Location

Rex Healthcare

Raleigh, North Carolina, 27607, United States

Location

Bon Secours Cancer Institute

Midlothian, Virginia, 23114, United States

Location

Related Links

• Lineberger Comprehensive Cancer Center website

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Fluorouracil; Leucovorin; Irinotecan; Bevacizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Melahat Canter
• Organization: UNC Lineberger Comprehensive Cancer Center

Melahat_Canter@med.unc.edu

(919) 962-0000

Study Officials

• Hanna Sannoff, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2014
• First Posted: May 14, 2014
• Study Start: May 6, 2014
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: May 18, 2025
• Results First Posted: May 18, 2025

Record last verified: 2025-04

Locations

US (7)