Effect of Curcumin on Dose Limiting Toxicity and Pharmacokinetics of Irinotecan in Patients With Solid Tumors

NCT01859858 | Completed Phase 1 DMC

• 1 other identifier: LCCC 1227
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

Curcumin is an extract of the tumeric root that has been shown to have anti-tumor properties in laboratory studies. Curcumin, and its parent spice, turmeric (curcuma longa), are the 4th most commonly purchased dietary supplement in the U.S. Many cancer patients take curcumin during their treatment for cancer because of the purported health benefits. This research study is designed to learn more about the safety, pharmacokinetics and effectiveness of irinotecan when given in combination with curcumin in patients with metastatic colorectal cancer. The study of how the body absorbs, processes and eliminates drugs is called pharmacokinetics (PK). One of the main purposes of this study is to better understand the interaction between curcumin and irinotecan by measuring levels of irinotecan in the blood (ie. measure irinotecan PK) when a patient also takes curcumin. Information collected from this study could result in improved dosing guidelines and lead to more effective treatment of your cancer with less toxicity.

Conditions

Advanced Colorectal Cancer

Keywords

mCRC (metastatic colorectal cancer); CRC (colorectal cancer); Advanced colorectal cancer; Metastatic colorectal cancer; Colon cancer

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  During Part 1 of study dose escalation will be used to determine the MTD of curcumin based on a DLT rate of 0.25 for the combination with irinotecan.

  28 days

• Pharmacokinetics of irinotecan

  The effect of curcumin on irinotecan PK will be evaluated via measurement of plasma Area Under the Curve (AUC) for irinotecan, with and without concomitant curcumin.

  28 days

• Pharmacokinetics of SN-38

  The effect of curcumin on SN-38 PK will be evaluated via measurement of plasma AUC of SN-38, with and without concomitant curcumin.

  28 days

Study Arms (2)

curcumin + irinotecan (part 1)

EXPERIMENTAL

Oral Curcumin (1, 2, 3,or 4 grams per day) for 4 days prior to irinotecan + 200 mg/m2 irinotecan IV, days 1 and 15

Dietary Supplement: curcumin; Drug: Irinotecan

curcumin + irinotecan (part 2)

EXPERIMENTAL

MTD oral Curcumin as determined in part 1 + 200 mg/m2 irinotecan IV, days 1 and 15

Dietary Supplement: curcumin; Drug: Irinotecan

Interventions

curcumin DIETARY_SUPPLEMENT

Also known as: tumeric, Curcuma longa, Meriva

curcumin + irinotecan (part 1); curcumin + irinotecan (part 2)

Irinotecan DRUG

Also known as: Camptosar

curcumin + irinotecan (part 1); curcumin + irinotecan (part 2)

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥21 years of age (no upper age limit)
• Histological or cytological documentation of metastatic adenocarcinoma of the colon or rectum. Biopsy of primary tumor alone is adequate if the patient has clear evidence of metastatic disease and/or elevated Carcinoembryonic antigen (CEA) and the treating physician does not feel biopsy of metastatic disease is clinically warranted.
• Prior therapy with oxaliplatin and a fluoropyrimidine is required. One prior line of therapy with irinotecan is allowed. Prior therapy with an anti-Epidermal Growth Factor Receptor (EGFR) agent is also allowed.
• Life expectancy of at least 3 months in opinion of treating investigator
• Eastern Cooperative Oncology Group performance status ≤1 (Appendix B)
• Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of treatment initiation with curcumin:
• 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) ≤ 3 x ULN
• Total bilirubin ≤ 1.5 x ULN
• Women of childbearing potential and male subjects must agree to use adequate contraception for the duration of study participation. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care.
• Medical oncologist agrees that four day window on curcumin alone is appropriate/safe prior to start of irinotecan for trial candidate.
• The subject is capable of understanding and complying with parameters as outlined in the protocol

You may not qualify if:

• Any prior allergies to curcumin or turmeric.
• Prior intolerance of irinotecan or necessity for dose reduction greater than 20%
• Patients who are already known homozygous for the UGT1A1\*28 allele (UDP-glucuronosyltransferase 1-1\*28), and patients of Asian descent homozygous or heterozygous for the UGT1A1\*6 allele will be excluded due to their altered irinotecan metabolism
• Pregnant or breastfeeding patients. Women of childbearing potential must have a documented negative pregnancy test a maximum of 7 days before start of treatment.
• History of Gilbert's syndrome
• Active cardiac disease including any of the following:
• Congestive heart failure ≥Class 2 according to New York Heart Association \[NYHA\] (see Appendix C)
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of Day 1 of irinotecan.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Ongoing infection \> Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0)
• Known history of human immunodeficiency virus (HIV) infection
• Symptomatic metastatic brain or meningeal tumors unless the patient is \>3 months from definitive therapy, has a negative imaging study within 4 weeks of irinotecan initiation, and is clinically stable with respect to the tumor at the time of study entry. Also, the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to D1 of treatment under this study)
• Inability to swallow oral medications or any malabsorption condition
• Patients with diarrhea CTCAE v4 grade ≥2
• Unresolved toxicity higher than CTCAE v. 4.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin-induced neurotoxicity (which must be ≤ Grade 2)

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (2)

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of North Carolina at Chapel Hill Lineberger Comprehensive cancer Center

Chapel Hill, North Carolina, 27509, United States

Location

Related Links

• UNC Lineberger Website

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Interventions

Curcumin; turmeric extract; Irinotecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Claire Asher, MD, MPH

  University of North Carolina at Chapel Hill Lineberger Comprehensive cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: May 22, 2013
• Study Start: June 1, 2013
• Primary Completion: October 5, 2016
• Study Completion: October 5, 2016
• Last Updated: December 4, 2023

Record last verified: 2020-06

Locations

US (2)