Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03928275
Recruitment Status : Not yet recruiting
First Posted : April 26, 2019
Last Update Posted : April 13, 2020
Sponsor:
Collaborator:
Nova Scotia Health Authority
Information provided by (Responsible Party):
Carman Giacomantonio, Nova Scotia Health Authority

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 Intervention/treatment Phase
Cutaneous Metastatic Melanoma Biological: Interleukin-2 Biological: Combination therapy Interleukin-2 and Bacillus Calmette Guerin 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 1, 2020
Estimated Primary Completion Date : September 1, 2025
Estimated Study Completion Date : September 1, 2030

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

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.
Other Name: Proleukin (Aldesleukin)

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).

Other Name: BCG, strain TICE (OncoTICE) and Proleukin (Aldesleukin)




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03928275


Contacts
Layout table for location contacts
Contact: Carman A Giacomantonio, MD 9024736177 carman.giacomantonio@nshealth.ca
Contact: Cheryl A Dean, MSc 9028301890 cheryldean597@gmail.com

Sponsors and Collaborators
Carman Giacomantonio
Nova Scotia Health Authority
Investigators
Layout table for investigator information
Principal Investigator: Carman A Giacomantonio, MD Nova Scotia Health Authority
Layout table for additonal information
Responsible Party: Carman Giacomantonio, Surgical Oncologist/General Surgeon/Professor, Nova Scotia Health Authority
ClinicalTrials.gov Identifier: NCT03928275    
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

Layout table for additional information
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, Nova Scotia Health Authority:
Interleukin-2
Bacillus Calmette Guerin
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Aldesleukin
Interleukin-2
BCG Vaccine
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Immunologic Factors