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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01859858
Recruitment Status : Active, not recruiting
First Posted : May 22, 2013
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

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.


Condition or disease Intervention/treatment Phase
Advanced Colorectal Cancer Dietary Supplement: curcumin Drug: Irinotecan Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Prospective Evaluation of the Effect of Curcumin on Dose-limiting Toxicity and Pharmacokinetics of Irinotecan in Colorectal Cancer Patients
Study Start Date : June 2013
Actual Primary Completion Date : October 5, 2016
Estimated Study Completion Date : October 5, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: curcumin + irinotecan (part 1)
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
Other Names:
  • tumeric
  • Curcuma longa
  • Meriva

Drug: Irinotecan
Other Name: Camptosar

Experimental: curcumin + irinotecan (part 2)
MTD oral Curcumin as determined in part 1 + 200 mg/m2 irinotecan IV, days 1 and 15
Dietary Supplement: curcumin
Other Names:
  • tumeric
  • Curcuma longa
  • Meriva

Drug: Irinotecan
Other Name: Camptosar




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 28 days ]
    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.

  2. Pharmacokinetics [ Time Frame: 28 days ]
    The effect of curcumin on irinotecan PK will be evaluated via measurement of plasma AUC (area under the curve) for irinotecan, with and without concomitant curcumin.

  3. Pharmacokinetics [ Time Frame: 28 days ]
    The effect of curcumin on SN-38 PK will be evaluated via measurement of plasma AUC of SN-38, with and without concomitant curcumin.



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Ages Eligible for Study:   21 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age ≥21 years of age (no upper age limit)
  2. 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.
  3. 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.
  4. Life expectancy of at least 3 months in opinion of treating investigator
  5. Eastern Cooperative Oncology Group performance status ≤1 (Appendix B)
  6. 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
  7. 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.
  8. Medical oncologist agrees that four day window on curcumin alone is appropriate/safe prior to start of irinotecan for trial candidate.
  9. The subject is capable of understanding and complying with parameters as outlined in the protocol
  10. Signed, Institutional Review Board(IRB)-approved written informed consent

Exclusion Criteria:

  1. Any prior allergies to curcumin or turmeric.
  2. Prior intolerance of irinotecan or necessity for dose reduction greater than 20%
  3. 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
  4. Pregnant or breastfeeding patients. Women of childbearing potential must have a documented negative pregnancy test a maximum of 7 days before start of treatment.
  5. History of Gilbert's syndrome
  6. 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)
  7. Ongoing infection > Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0)
  8. Known history of human immunodeficiency virus (HIV) infection
  9. 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)
  10. Inability to swallow oral medications or any malabsorption condition
  11. Patients with diarrhea CTCAE v4 grade ≥2
  12. 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)
  13. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  14. Patients unwilling or unable to refrain from use of moderate or strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) (Appendix A)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01859858


Locations
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United States, Indiana
IU Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, North Carolina
University of North Carolina at Chapel Hill Lineberger Comprehensive cancer Center
Chapel Hill, North Carolina, United States, 27509
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
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Principal Investigator: Gary Asher, MD, MPH University of North Carolina at Chapel Hill Lineberger Comprehensive cancer Center

Additional Information:
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Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01859858     History of Changes
Other Study ID Numbers: LCCC 1227
First Posted: May 22, 2013    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
mCRC (metastatic colorectal cancer)
CRC (colorectal cancer)
Advanced colorectal cancer
Metastatic colorectal cancer
Colon cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Curcumin
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents