Pilot Trial of Colchicine in Urothelial Cancer and Other Solid Tumors
Study Details
Study Description
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 metastatic solid tumors (15 patients will receive low-dose colchicine and 15 for high-dose colchicine). In Cohort 2, 15 patients with post-radical surgery for high-risk clinically localized urothelial cancer will be enrolled. 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 three cycles of colchicine, where the baseline value is measured before any treatment is initiated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 low-dose colchicine Participants with metastatic solid tumors who will receive low-dose colchicine (0.6 mg oral BID) |
Drug: Colchicine
Patients will receive 3 cycles of colchicine in the absence of prohibitive toxicity of disease progression (1 cycle = 28 days).
|
| 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 3 cycles of colchicine in the absence of prohibitive toxicity of disease progression (1 cycle = 28 days).
|
| 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 3 cycles of colchicine in the absence of prohibitive toxicity of disease progression (1 cycle = 28 days).
|
Outcome Measures
Primary Outcome Measures
- Percent Change in Peripheral blood CRP level [Baseline and Within 28 days of completing cycle 3 (each cycle is 28 days)]
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 who receive a 3-cycle treatment, it will be the maximum percentage decline during the 3-cycle treatment period. For a patient who receive colchicine less than 3 cycles, it will be the maximum percentage decline from baseline to the last day of treatment.
Eligibility Criteria
Criteria
Inclusion Criteria
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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.
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Age ≥ 18 years at the time of consent.
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ECOG Performance Status of 0-1 within 28 days prior to registration.
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Elevated peripheral blood CRP level (> 5 mg/L) documented on routine bloodwork within 28 days prior to registration.
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Cohort 1:
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Histological or cytologically confirmed solid tumor.
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Metastatic disease which has progressed despite at least 2 lines of standard therapy or for which no standard therapy exists.
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Measurable disease as per RECIST 1.1 or evaluable disease (i.e. bone only metastatic disease or elevated tumor markers)
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Cohort 2:
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History of urothelial cancer post radical cystectomy, nephroureterectomy, or ureterectomy, at high risk for metastatic recurrence as defined by: (a) ≥ pT3 and /or pN+ urothelial cancer in the absence of neoadjuvant chemotherapy or (b) ≥ ypT2 and /or ypN+ urothelial cancer after prior neoadjuvant chemotherapy
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Ineligible for standard adjuvant therapy (e.g., cisplatin ineligible but otherwise meeting eligibility), or for whom no standard adjuvant therapy exists (e.g., residual ≥ ypT2 and /or ypN+ urothelial cancer after prior neoadjuvant chemotherapy), or after completion of standard adjuvant therapy.
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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.
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Demonstrate adequate organ function as defined below. All screening labs to be obtained within 14 days prior to registration.
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White blood cell (WBC) ≥ 2.5 K/mm3
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Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
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Hemoglobin (Hgb) ≥ 8 g/dL
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Calculated GFR ≥ 50 cc/min or creatinine ≤ 1.5 mg/dl (The CKD-EPI equation will be used to calculate GFR)
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Bilirubin ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
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Aspartate aminotransferase (AST) ≤ 2.5 × ULN
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Alanine aminotransferase (ALT) ≤ 2.5 × ULN
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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.
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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).
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HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
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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.
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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
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Already taking long term colchicine for any other reason.
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Active infection requiring systemic therapy.
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Pregnant or breastfeeding.
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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.
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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.
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Active central nervous system (CNS) metastases.
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Treatment with any investigational drug within 30 days prior to registration.
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Need for concomitant treatment with moderate or strong CYP3A4 inhibitors or P-gp inhibitors.
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Rheumatoid arthritis, vasculitis, or systemic lupus erythematosus requiring active treatment.
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Myocardial infarction within the prior last 6 months and/or ≥ Class III New York Heart Association heart failure.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
Sponsors and Collaborators
- Icahn School of Medicine at Mount Sinai
Investigators
- Principal Investigator: Deborah Doroshow, Icahn School of Medicine at Mount Sinai
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY-21-01175