Curcumin in Combination With 5FU for Colon Cancer

• ClinicalTrials.gov Identifier: NCT02724202
• Recruitment Status: Unknown
• First Posted: March 31, 2016
• Last Update Posted: January 18, 2020
• Sponsor: Baylor Research Institute
• Information provided by (Responsible Party): Baylor Research Institute

Tracking Information

• First Submitted Date: March 16, 2016
• First Posted Date: March 31, 2016
• Last Update Posted Date: January 18, 2020
• Study Start Date: March 2016
• Estimated Primary Completion Date: March 13, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 25, 2016)

Determine the safety using curcumin in patients with metastatic colon cancer; where toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. [ Time Frame: 12 weeks ]

Events will be recorded from the time of informed consent signature through the 30 days following the last study treatment.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 31, 2016)

• Overall Response [ Time Frame: 12 months ]
  Recorded from the start of the treatment until disease progression/recurrence. The patient's best response assignment will depend on the finding of target and non-target disease and will also take into consideration the appearance of new lesions.
• Evidence of altered biomarker status (circulating DNA methylation status, miRNA profile) at 8 weeks post-treatment according to RECIST version 1.1 and survival criteria. [ Time Frame: Baseline, Week 2, Week 8 ]
  Blood will be collected at baseline, after completing one cycle of curcumin treatment (2 weeks), and after completing three 2 week-cycles of 5FU (6 weeks) for inflammatory and epigenetic chemoresponsive biomarker profiling.
• Duration of response [ Time Frame: 12 months ]
• Duration of progression free survival [ Time Frame: 12 months ]
• Duration of overall survival [ Time Frame: 12 months ]
• Duration of Quality of Life [ Time Frame: Baseline, 12 months ]
  All subjects will complete the quality of life survey at Baseline, 5FU treatment visits and follow-up visits.

Original Secondary Outcome Measures (submitted: March 25, 2016)

• Overall Response [ Time Frame: 12 months ]
  Recorded from the start of the treatment until disease progression/recurrence. The patient's best response assignment will depend on the finding of target and non-target disease and will also take into consideration the appearance of new lesions.
• Evidence of altered biomarker status (circulating DNA methylation status, miRNA profile) at 8 weeks post-treatment according to RECIST version 1.1 and survival criteria. [ Time Frame: 8 weeks ]
  Blood will be collected at baseline, after completing one cycle of curcumin treatment (2 weeks), and after completing three 2 week-cycles of 5FU (6 weeks) for inflammatory and epigenetic chemoresponsive biomarker profiling.
• Duration of response [ Time Frame: 12 months ]
• Duration of progression free survival [ Time Frame: 12 months ]
• Duration of overall survival [ Time Frame: 12 months ]
• Duration of Quality of Life [ Time Frame: 12 months ]
  All subjects will complete the quality of life survey at Baseline, 5FU treatment visits and follow-up visits.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Curcumin in Combination With 5FU for Colon Cancer
• Official Title: A Pilot, Feasibility Study of Curcumin in Combination With 5FU for Patients With 5FU-Resistant Metastatic Colon Cancer
• Brief Summary: The purpose of this study is to test the safety and find the response rate of combining the dietary supplement, curcumin, with the standard of care, FDA-approved chemotherapy drug 5-fluorouracil (5FU, Adracil) and see what effects (good and bad) that the combined treatments have on colon cancer.
• Detailed Description: Confirm clinical safety and identify clinical response rate of combination treatment with curcumin and 5FU in chemorefractory CRC patients. To determine whether curcumin administration induces systemic alterations in inflammatory and epigenetic biomarkers in patients with chemoresistant metastatic colorectal cancer (CRC). To correlate altered biomarker findings with clinical response according to RECIST V1.1 and survival criteria.
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colon Cancer

Intervention

• Drug: Curcumin
  Curcumin is supplied as soft-gel capsule. It is a micronized rhizome extract containing phospholipids and 500mg of pure curcuminoids (95% curcumin, 5% desmethoxycurcumin) suspended in turmeric essential oil.
  Other Name: BCM-95
• Drug: 5-flurorouracil
  Fluorouracil is an anti-cancer (antineoplastic or cytotoxic) chemotherapy drug. Fluorouracil is classified as an antimetabolite.
  Other Names:

  • 5FU
  • Adracil

Study Arms

Experimental: Open Label

All subjects will receive induction oral curcumin 500 mg twice per day for 2 weeks. Patients will continue on curcumin at same dose for an additional 6 weeks while being treated with 3 cycles of 5FU.

Interventions:

• Drug: Curcumin
• Drug: 5-flurorouracil

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: May 20, 2019): 13
• Original Estimated Enrollment (submitted: March 25, 2016): 14
• Estimated Study Completion Date: June 13, 2020
• Estimated Primary Completion Date: March 13, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female 18 years or older, at the time of signing the informed consent.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Histologically or cytologically confirmed diagnosis of metastatic colorectal cancer that is not response to standard 5FU based therapies.
• Performance Status (PS) score of 0 to 2 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• Able to swallow and retain oral medication.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 mili-internation unit (MIU)/ml and estradiol <40 pg/ml (140pmol/L) is confirmatory
• Child-bearing potential and agrees to use a contraception method of abstinence, intrauterine device (IUD), barrier methods or birth control pills prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point and until three months after the last dose of the study medication.
• Male subjects must agree to use a method of contraception. This criterion must be followed from the time of the first dose of study medication until three months after the last dose of study medication.
• Adequate organ system function defined as follows:

System Laboratory Values Hematologic Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L Hemoglobin ≥ 9.5 g/dL Platelets ≥ 75 x 10^9/L For subjects not on warfarin-based anticoagulants: Prothrombin time/International normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.1x upper limit of normal (ULN) INR (subjects on warfarin-based anticoagulant): 2-3 x ULN Hepatic Total bilirubin ≤ 1.5x ULN (isolated bilirubin > 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) Aspartate aminotransferase (AST) and alanine transaminase (ALT) 1 ≤ 1.5x ULN Albumin ≥ 2.5 g/dL Renal Creatinine ≤ ULN; or Calculated creatinine clearance2 ≥ 50 mL/min; or Metabolic Fasting Serum Glucose < 250 mg/dL Cardiac Left Ventricular Ejection fraction (LVEF) ≥ lower limit of normal (LLN) by echocardiogram (ECHO) Blood pressure Systolic < 160 mm Hg and Diastolic < 100 mm Hg.

1. If liver metastases are present, AST and ALT ≤ 2.5x ULN is permitted
2. As calculated by Cockcroft-Gault formula.

Exclusion Criteria:

• Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapy including investigational drugs within 28 days or 5 half-lives, whichever is shorter prior to the first dose of any one of the investigational drugs described in this study.
• Unresolved toxicity by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE V4) of > Grade 1 from previous anti-cancer therapy.
• Presence of active GI disease or other condition that could affect gastrointestinal absorption (malabsorption syndrome) or predispose a subject to GI ulceration.
• Evidence of mucosal or internal bleeding
• Any major surgery within the last four weeks
• Uncontrolled diabetes mellitus
• Any malignancy related to human immunodeficiency virus (HIV), known history of HIV, history of known Hepatitis B virus (HBV) surface antigen positivity (subjects with documented laboratory evidence of HBV clearance may be enrolled) or positive Hepatitis C virus (HCV) antibody.
• Known active infection requiring parenteral or oral anti-infective treatment.
• Subjects with brain metastases are excluded if their brain metastases are:
• Symptomatic
• Treated (surgery, radiation therapy) but not clinically and radiographically stable one month after therapy (as assessed by at least 2 distinct contrast enhanced MRI or CT scans over at least a one month period), or
• Asymptomatic and untreated but > 1 cm in the longest dimension
• History or evidence of current clinically significant uncontrolled arrhythmias.
• Subjects with controlled atrial fibrillation for >1 month prior to study Day 1 are eligible.
• History of acute coronary syndromes (including unstable angina), myocardial infarction, coronary angioplasty, or stenting or bypass grafting within six months of screening.
• Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Any serious or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject's safety or providing informed consent.
• Known immediate or delayed hypersensitivity to any of the components of the study treatment(s).
• Evidence of severe or uncontrolled systemic diseases (unstable or uncompensated respiratory, hepatic, renal, or cardiac disease, including unstable hypertension).
• Pregnant or lactating females.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02724202
• Other Study ID Numbers: 014-143
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Baylor Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Baylor Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: John Preskitt, MD; Baylor University Medical Center/Texas Oncology, PA

• PRS Account: Baylor Research Institute
• Verification Date: January 2020