Genotype-Directed Dose-Escalation Study of Irinotecan in Patients With Advanced Solid Tumors

A Phase I Genotype-Directed Dose-Escalation Study of Irinotecan (NSC616348, CPT-11, Camptosar) in Patients With Advanced Solid Tumors

Describe the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of irinotecan in cancer patients with advanced solid tumors with UGT1A1 6/6 and 6/7 genotypes.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed solid tumor or lymphoma that is appropriate for treatment with irinotecan.
• 18 years or older
• ECOG performance status 0-1
• Life expectancy of greater than 12 weeks.

• Normal organ and marrow function as defined below:

  • leukocytes ≥ 3,000/μl
  • absolute neutrophil count ≥ 1,500/μl
  • platelets ≥ 100,000/μl
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN (≤5 X ULN in patients with hepatic metastases)
  • creatinine within normal institutional limits OR
  • glomerular filtration rate ≥50 ml/min/1.73 m2 for patients with creatinine levels above institutional normal as calculated by the modified MDRD equation recommended by the National Kidney Disease Education Program
• Measurable or assessable disease.
• Able to understand and the willing to sign a written informed consent document.
• Women of child-bearing potential and men and their partners must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.
• Patients with UGT1A1 genotype 6/6, 6/7, and 7/7. Patients with either one or two of the rare alleles (i.e., 5 allele and 8 allele), and carriers of the *6 allele will not be enrolled in the study. Patients will have blood drawn for genotyping upon signing the informed consent form for this study.
• Patients taking any statin therapy should interrupt the dosing of the statin for the 3 days before and after the administration of irinotecan at each cycle

Exclusion Criteria:

• Biologic therapy, chemotherapy, radiotherapy, or investigational agent within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Cannot be receiving any other investigational agents.
• Use of colony growth factor within 3 week prior to study entry.
• Post-transplant patients, as they may be subject to severe neutropenia.
• Uncontrolled brain metastases. Patients with brain metastases must have stable neurologic status off of steroids and anticonvulsants for at least 4 weeks and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because irinotecan is an agent with the potential for teratogenic or abortifacient effects. Breastfeeding should be stopped.
• HIV-positive patients, as patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• History of inflammatory bowel disease requiring therapy or patients with chronic diarrhea syndromes or paralytic ileus.
• Patients who have undergone a major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to start of therapy cannot participate.
• Patients with prior pelvic irradiation cannot participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm	Drug: Irinotecan; 90 minute IV infusion once every 3 weeks. Dose will be based on sex and genotype determination.; Other Names: Camptosar; CPT-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
maximum tolerated dose	3 weeks
dose-limiting toxicity	3 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
pharmacokinetics	3 weeks
anti-tumor response	6 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Federico Innocenti, MD, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: June 27, 2008
• First Submitted That Met QC Criteria: July 1, 2008
• First Posted (Estimate): July 2, 2008

Study Record Updates

• Last Update Posted (Estimate): January 4, 2017
• Last Update Submitted That Met QC Criteria: January 3, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: 13934B