Pilot Trial of Colchicine in Urothelial Cancer and Other Solid Tumors

Colchicine to Suppress Pro-tumorigenic Inflammation in Patients With Urothelial Cancer and Other Solid Tumors

This open-label, non-randomized study aims to determine the anti-inflammatory effect of colchicine on the reduction of peripheral blood CRP in patients with solid tumors or localized urothelial cancer. There are two cohorts, which will enroll separately and parallelly. Cohort 1 will include two successive groups with advanced/recurrent solid tumors (15 patients will receive low-dose colchicine and 15 for high-dose colchicine) who will receive 14 days of colchicine. In Cohort 2, 15 patients with post-radical surgery for high-risk clinically localized urothelial cancer will be enrolled. They will receive one 28-day cycle of colchicine. The primary outcome, post-treatment decline in CRP level, a continuous measure, will be defined as the maximum percentage decline from baseline in post-treatment CRP value within two weeks of colchicine (Cohort 1) or one cycle of colchicine (cohort 2), where the baseline value is measured before any treatment is initiated.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Solid Tumor; Urothelial Cancer
• Intervention / Treatment: Drug: Colchicine

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Natalie Lucas; Phone Number: 929-489-5016; Email: natalie.lucas@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Principal Investigator: Deborah B Doroshow, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration. ECOG 2 is allowed for patients on Cohort 1.

• Cohort 1:

  • Histological or cytologically confirmed solid tumor.
  • Metastatic or recurrent disease
  • Elevated peripheral blood CRP level (> 5 mg/L) documented on routine bloodwork within 14 days or registration.

• Cohort 2:

  • History of urothelial cancer post radical cystectomy, nephroureterectomy, or ureterectomy
  • Eligible and planned for standard of care adjuvant nivolumab in the opinion of the treating investigator
  • Elevated peripheral blood CRP level (> 5 mg/L) documented on routine bloodwork at a minimum of 30 days and a maximum of 120 days after surgical resection and within 14 days prior to registration.
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least 15 unstained slides. If archival tissue is not available, enrollment will be considered on a case by case basis after discussion with the Principal Investigator.

• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 14 days prior to registration.

  • White blood cell (WBC) ≥ 2.5 K/mm3
  • Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
  • Hemoglobin (Hgb) ≥ 8 g/dL
  • Calculated GFR ≥ 50 cc/min or creatinine ≤ 1.5 mg/dl (The CKD-EPI equation will be used to calculate GFR)
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN or < 5xULN for patients in Cohort 1 with liver metastases
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN or < 5xULN for patients in Cohort 1 with liver metastases
• Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. See section 5.5 for definition of childbearing potential.
• Females of childbearing potential must be willing to abstain from heterosexual activity or to use an effective method(s) of contraception from the time of informed consent, during the study until after the last dose of study drug(s). Males must be willing to abstain from heterosexual activity or to use an effective method(s) of contraception from initiation of treatment until after the last dose of study drug(s).
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria

• Already taking long term colchicine for any other reason.
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding.
• Prior cancer treatment must be completed at least 30 days prior to registration, or within 5 half-lives, and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
• Active central nervous system (CNS) metastases.
• Treatment with any investigational drug within 30 days prior to registration.
• Need for concomitant treatment with moderate or strong CYP3A4 inhibitors or P-gp inhibitors.
• Rheumatoid arthritis, vasculitis, systemic lupus erythematosus, or other autoimmune condition requiring active systemic treatment.
• Myocardial infarction within the prior last 6 months and/or ≥ Class III New York Heart Association heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 high-dose colchicine; Participants with metastatic solid tumors who will receive high-dose colchicine (0.6 mg oral TID)	Drug: Colchicine; Patients will receive 14 days of colchicine in the absence of prohibitive toxicity of disease progression
Experimental: Cohort 2 Participants with post-radical surgery; Participants with post-radical surgery for high-risk clinically localized urothelial cancer will receive colchicine 0.6 mg oral BID.	Drug: Colchicine; Patients will receive 14 days of colchicine in the absence of prohibitive toxicity of disease progression
Experimental: Cohort 1 low-dose colchicine; Participants with advanced/recurrent solid tumors who will receive low-dose colchicine (0.6 mg oral BID)	Drug: Colchicine; Patients will receive 14 days of colchicine in the absence of prohibitive toxicity of disease progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Peripheral blood CRP level	The primary outcome, post-treatment decline in peripheral blood CRP level, a continuous measure, will be defined as the maximum percent decline of post-treatment CRP from baseline obtained during the treatment period, where the baseline value is measured before any treatment initiated For a patient with an advanced/recurrent solid tumor who receive 2-weeks of treatment, it will be the maximum percentage decline during the 28 days of treatment. For a patient who receive colchicine less than 28 days, it will be the maximum percentage decline from baseline to the last day of treatment.	Baseline and Within 28 days

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Deborah Doroshow, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 5, 2022
• First Submitted That Met QC Criteria: March 5, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: STUDY-21-01175

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will not be shared due to the small cohort size.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No