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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/26/2021.

The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma

Clinicaltrials.gov identifier NCT03928275

Recruitment Status Not yet recruiting

First Posted April 26, 2019

Last update posted April 13, 2020

Study Description

Brief summary:

The investigators aim to include 100 local participants over the next 5 years in a two-stage sequential randomized interventional study of intralesional Interleukin-2 (IL-2) and Bacillus Calmette Guerin (BCG) to assess the utility of treating cutaneous metastatic melanoma (CMM).

  • Condition or Disease:Cutaneous Metastatic Melanoma
  • Intervention/Treatment: Biological: Interleukin-2
    Biological: Combination therapy Interleukin-2 and Bacillus Calmette Guerin
  • Phase: Phase 2/Phase 3
Detailed Description

In the first stage of the study, all consenting CMM patients will be randomized and will receive 4 treatments of either intralesional IL-2 or intralesional IL-2 and BCG. We hypothesize that patients with MM (stage 3C or 4a with a minimum of 4 lesions) that receive combination therapy (IL-2/BCG) in the first stage of treatment will have a higher complete response (iCR) rate compared to IL-2 therapy alone. Response to stage-one treatment will be monitored and patient response to treatment will be determined and reported according to Immune Response Evaluation Criteria in Solid Tumours (iRECIST) guidelines. Based on response to stage-one treatment, patients will be placed into a response group before entering stage two. For stage two of the trial, patients will be randomized again, and placed into a treatment group; Il-2, IL-2 and BCG, BCG, or Discontinue Treatment. Response to treatment will be monitored and patient response to treatment will be determined and reported according to iRECIST guidelines. All patients will have lesions biopsied following standard surgical practice techniques and will provide urine and blood for analysis. Tissue samples will be assessed for immune system activity and transcriptome analysis, and urine and blood will be assessed for immune cell populations and markers. All patients will be followed for 5 years post treatment, and patient disease and survival status will be recorded according to iRECIST.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 100 participants
  • Allocation: Randomized
  • Intervention Model: Sequential Assignment
  • Intervention Model Description: Patients will be randomized to first stage treatment and allocated to 1) IL-2 or 2) IL-2/BCG treatment. First stage treatment patients receive 4 treatments of 1) IL-2 or 2) IL-2 and BCG. Patient response will be determined for treatment groups following iRECIST guidelines as; 1) complete responder, 2) partial responder, or 3) stable disease. In second stage treatment, patients who completely respond to first stage treatment will be randomized to 1) discontinue treatment and followed every 3 mos for 2 yrs and then every 6 mos from yrs 3-5, or 2) will receive 2 additional treatments and then followed every 3 mos for 2 yrs and then every 6 mos from yrs 3-5. Patients that do not completely respond to first stage treatment, will be re-staged using a PET/CT scan. Patients not requiring escalation to systemic therapy will be randomized and advance to second stage treatment (IL-2, IL-2 and BCG, or BCG).
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma
  • Estimated Study Start Date: September 2020
  • Estimated Primary Completion Date: September 2025
  • Estimated Study Completion Date: September 2030
Arms and interventions
Arm Intervention/treatment
Experimental: Intralesional IL-2 Treatment
CMM patients will received 4 treatments of intralesional Interleukin-2 two weeks apart over an eight week period.
Biological: Interleukin-2
IL-2 is prepared as 4 million International Units (IU) per 0.8ml at a total dose of 500,000 IU in 0.1ml of sterilized saline (0.9%, m/v)/lesion.
Experimental: Combination therapy: Intralesional IL-2 and BCG Treatment
CMM patients will receive 4 treatments of combination therapy intralesional Interleukin-2 and Bacillus Calmette Guerin two weeks apart over an eight week period.
Biological: Combination therapy Interleukin-2 and Bacillus Calmette Guerin
BCG (OncoTICE solutions 1-8 x 10-8 Colony Forming Units (CFU)) will be administered at a maximum dose of 3.2 million CFU per treatment at a maximum of 1.6 million CFU per lesion (max 2 lesions). IL-2 is prepared as 4 million International Units (IU) per 0.8ml at a total dose of 500,000 IU in 0.1ml of sterilized saline (0.9%, m/v)/lesion (in remaining lesions).
Outcome Measures
  • Primary Outcome Measures: 1. Number of CMM participants that respond to IL-2 compared to the number of participants that respond to IL-2 and BCG. [ Time Frame: 5 years ]
    The primary outcome measure is the achievement of a superior response rate in patients receiving combination IL-2/BCG treatment compared to patients receiving IL-2 alone. Patient response to treatment will be monitored and patients will be categorized as 1) complete responders, 2) partial responders or 3) stable disease. Data will be analyzed by one-way ANOVA to compare proportion outcomes amongst treatment and response groups.
  • Secondary Outcome Measures: 1. Number of patients that respond to the addition of BCG in stage two compared to the number of patients respond to continued IL-2 treatment. [ Time Frame: 5 years ]
    The achievement of a superior response rate in patients that partially respond or do not respond to single agent IL-2 in stage one, with the addition of BCG treatment in stage two. Patient response to treatment will be monitored and patients will be categorized as 1) complete responders, 2) partial responders or 3) stable disease. Data will be analyzed by one-way ANOVA to compare proportion outcomes amongst treatment and response groups.
  • 2. Assessment of overall survival in stage one treatment [ Time Frame: 5 years ]
    Complete responders to stage-one treatments will be assessed to determine if there is a difference in overall survival between participants that continue treatment compared to participants that discontinue treatment. Data will be assessed using Kaplan-Meier methods and compared using Log-rank tests.
  • 3. Assessment of overall survival in stage two treatment [ Time Frame: 5 years ]
    Response groups following stage-two treatments will be assessed to determine if there is a difference in overall survival amongst response groups. Data will be assessed using Kaplan-Meier methods and compared using Log-rank tests.
  • 4. Assessment of Disease Progression Within Stage of Disease: Number of stable and/or new metastasis [ Time Frame: 5 years ]
    All patients will be followed every 3 months for 2 years and then biannual assessments for years 3-5 after the initial intervention to assess the number of stable or new lesions amongst treatment response groups. Number (integer value) of new metastases will be recorded as a part of this assessment. Data will be compared using a one-way ANOVA. Post-Hoc analysis will be conducted when needed.
  • 5. Assessment of Metastasis: Lesion size (2 dimensions) [ Time Frame: 5 years ]
    Assessment of Metastasis - All patients will be followed every 3 months for 2 years and then biannual assessments for years 3-5 after the initial intervention to assess change in lesion size according to iRECIST guidelines. Lesions will be measured in mm in 2 dimensions as part of this assessment. Data will be compared using a one-way ANOVA. Post-Hoc analysis will be conducted when needed.
  • 6. Assessment of Systemic Immune Response: FACs analysis [ Time Frame: 5 years ]
    Plasma collected from patient blood samples will be used in FACs analysis to assess circulating immunomodulators (cytokines and chemokines) before, during and after, treatment.
  • 7. Assessment of Systemic Immune Response: Metabolomics [ Time Frame: 5 years ]
    Blood and urine samples will be evaluated by mass spectrometry, to assess and compare the metabolome amongst treatment groups.
  • 8. Assessment of RNA genetic profile [ Time Frame: 5 years ]
    RNA analysis of biopsied tissue will be compared. Patient tumor tissue (from biopsy) collected during the study will be utilized in an experimental study designed to characterized the immune response involved before, during and after intralesional IL-2 and/or BCG immunotherapy.
Eligibility Criteria
  • Ages Eligible for Study: 18 to 80 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

- Patient with cutaneous metastatic melanoma.

- Has 4 or more melanoma lesions.

- Between18 and 80 years of age.

Exclusion Criteria:

- Immunocompromized.

- Receiving immuno-therapy for other diagnosis.

- Inflammatory disease.

- Autoimmune disease.

- Pregnant

- HIV

- Test positive for TB

Contacts and Locations
Contacts

Contact: Carman A Giacomantonio, MD 9024736177 carman.giacomantonio@nshealth.ca

Contact: Cheryl A Dean, MSc 9028301890 cheryldean597@gmail.com

Locations
Sponsors and Collaborators

Carman Giacomantonio

Nova Scotia Health Authority

Investigators

Principal Investigator: Carman A Giacomantonio, MD Nova Scotia Health Authority

More Information
  • Responsible Party: Carman Giacomantonio
  • ClinicalTrials.gov Identifier: NCT03928275 History of Changes
  • Other Study ID Numbers: 14549
  • First Posted: April 26, 2019 Key Record Dates
  • Last Update Posted: April 13, 2020
  • Last Verified: April 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • 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.: Yes
  • Keywords provided by Carman Giacomantonio: Interleukin-2 Bacillus Calmette Guerin
  • Additional relevant MeSH terms: Melanoma