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

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ClinicalTrials.gov Identifier: NCT03928275
Recruitment Status : Not yet recruiting
First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Collaborator:
Nova Scotia Health Authority
Information provided by (Responsible Party):
Carman Giacomantonio, Nova Scotia Health Authority

Brief Summary:
The investigators aim to include 40 local participants over the next 5 years in a non-randomized controlled study of intralesional Interleukin-2 (IL-2) and Bacillus Calmetter 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 Bacillus Calmette Guerin and Interleukin-2 Phase 2 Phase 3

Detailed Description:
All consenting CMM patients will receive 4 treatments of intralesional IL-2 and response to treatment will be monitored. Partial responders and non-responders to the first 4 IL-2 treatments will receive an additional 2 treatments of a combination therapy of intralesional IL-2 and BCG and response to treatment will be monitored. Patients who have a partial response to IL-2/BCG combination therapy will continue with IL-2 treatment. Non responders will discontinue all IL-2/BCG treatment and be referred for systemic therapy. The investigators hypothesize that patients that have a partial immune response to IL-2 alone will benefit from the addition of BCG, boosting local immune response by stimulating a robust TIL response that could ultimately prevent distant metastasis. Further the investigators hypothesize that patients that do not have a response to intralesional IL-2 will also not respond to intralesional BCG. The belief is that combination immunotherapy is the future of CMM therapy. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: All patients will receive 4 treatments of intralesional IL-2 and response to treatment will be monitored. Complete responders will discontinue treatment. Partial responders and non-responders to the first 4 IL-2 treatments will receive an additional 2 treatments of a combination therapy of intralesional IL-2 and BCG and response to treatment will be monitored. Patients who have a partial response to IL-2/BCG combination therapy will continue with IL-2 treatment. Non responders will discontinue all Il-2/BCG treatment and be referred for systemic therapy.
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 : January 1, 2020
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Complete Responder
Stage 3C or 4a CMM patients who completely respond to the first 4 treatments of intralesional interleukin-2 two weeks apart over an eight week period will be included in this arm.
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: Partial Responder
Stage 3C or 4a CMM patients who partially respond to the first 4 treatments of intralesional interleukin-2 two weeks apart over an eight week period will be included in this arm.
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)

Biological: Combination therapy Bacillus Calmette Guerin and Interleukin-2

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)

Experimental: Non Responder
Stage 3C or 4a CMM patients who do not respond to the first 4 treatments of intralesional interleukin-2 two weeks apart over an eight week period will be included in this arm.
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)

Biological: Combination therapy Bacillus Calmette Guerin and Interleukin-2

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 completely respond to the first 4 intralesional injections of IL-2 [ Time Frame: 5 years ]
    Number of CMM participants (stage 3C or 4a, with a minimum of 6 lesions) after the first 4 treatments of intralesional IL-2 are complete responders (assessed as tumor regression compared to baseline and no viable disease).

  2. Number of CMM participants that partially respond to the first 4 intralesional injections of IL-2 [ Time Frame: 5 years ]
    Number of CMM participants (stage 3C or 4a, with a minimum of 6 lesions) after the first 4 treatments of intralesional IL-2 are partial responders (assessed as partial tumor regression compared to baseline and viable disease).

  3. Number of CMM participants that do not respond to the first 4 intralesional injections of IL-2 [ Time Frame: 5 years ]
    Number of CMM participants (stage 3C or 4a, with a minimum of 6 lesions) after the first 4 treatments of intralesional IL-2 are non responders (no tumor regression compared to baseline and viable disease).

  4. Number of CMM participants that do not completely respond to the first 4 treatments of intralesional IL-2 (assessed in outcomes 2 and 3), respond to combination IL-2 and BCG treatments. [ Time Frame: 5 years ]
    Number of CMM participants that are partial responders (assessed in outcome 2) or non-responders (assessed in outcome 3) to intralesional IL-2 after the first 4 treatments, benefit from the addition of 2 treatments 2 weeks apart of combination therapy of intralesional BCG (in 2 lesions) and IL-2 (in remaining lesions). A benefit assessed as complete response (tumor regression compared to baseline and no viable disease).

  5. Assessment of Metastasis: Number of 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 disease metastasis in treatment groups. Number (integer value) of new metastases will be recorded as a part of this assessment.

  6. Assessment of Metastasis: Stage of progression [ 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 disease metastasis in treatment groups. Stage of progression will be analysed as a categorical variable (Stage 0, Stage I, Stage II, Stage III, or Stage IV).


Secondary Outcome Measures :
  1. 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 determine what immune modulators are involved before, during and after intralesional IL-2 and/or BCG immunotherapy.

  2. Assessment of Systemic Immune Response: FACs analysis [ Time Frame: 5 years ]
    Plasma collected from patient blood samples will be used in FACs analysis at Dalhousie University's Flow Cytometry Core Facility to assess circulating immunomodulators (cytokines and chemokines) before, during and after, treatment amongst different response groups.

  3. Assessment of Systemic Immune Response: Metabolomics [ Time Frame: 5 years ]
    Blood and urine samples will be prepared and stored in Dr. Carman Giacomantonio's laboratory at Dalhousie University for future metabolomic analyses. Sample will be evaluated by mass spectrometry, to assess and compare systemic immune response amongst treatment groups. All metabolomics will occur at Dalhousie's Proteomics and Mass Spectrometric Core Facility located in the Life Sciences Research Institute.



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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 6 or more melanoma lesions.
  • Between18 and 80 years of age.

Exclusion Criteria:

  • Immunocompromized.
  • Receiving immuno-therapy for other diagnosis.
  • Inflammatory disease.
  • Autoimmune disease.

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

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Responsible Party: Carman Giacomantonio, Surgical Oncologist/General Surgeon/Professor, Nova Scotia Health Authority
ClinicalTrials.gov Identifier: NCT03928275     History of Changes
Other Study ID Numbers: 14549
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Interleukin-2
Aldesleukin
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