Pilot Trial of Colchicine in Urothelial Cancer and Other Solid Tumors

NCT05279690 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: STUDY-21-01175
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Urothelial Cancer; Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Cohort 1 low-dose colchicine

EXPERIMENTAL

Participants with advanced/recurrent solid tumors who will receive low-dose colchicine (0.6 mg oral BID)

Drug: Colchicine

Cohort 1 high-dose colchicine

EXPERIMENTAL

Participants with metastatic solid tumors who will receive high-dose colchicine (0.6 mg oral TID)

Drug: Colchicine

Cohort 2 Participants with post-radical surgery

EXPERIMENTAL

Participants with post-radical surgery for high-risk clinically localized urothelial cancer will receive colchicine 0.6 mg oral BID.

Drug: Colchicine

Interventions

Colchicine DRUG

Patients will receive 14 days of colchicine in the absence of prohibitive toxicity of disease progression

Cohort 1 high-dose colchicine; Cohort 1 low-dose colchicine; Cohort 2 Participants with post-radical surgery

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Deborah Doroshow

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 5, 2022
• First Posted: March 15, 2022
• Study Start: February 14, 2022
• Primary Completion: December 16, 2024
• Study Completion: December 16, 2024
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)