Clinical trial NCT03928275: The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma
Official title: The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Cutaneous Metastatic Melanoma
Keywords: Interleukin-2
Bacillus Calmette Guerin
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Nova Scotia Health Authority
First posted: 2019-04-26
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: Number of CMM participants that respond to IL-2 compared to the number of participants that respond to IL-2 and BCG.
timeFrame: 5 years
Secondary outcomes:
measure: 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.
timeFrame: 5 years
measure: Assessment of overall survival in stage one treatment
timeFrame: 5 years
measure: Assessment of overall survival in stage two treatment
timeFrame: 5 years
measure: Assessment of Disease Progression Within Stage of Disease: Number of stable and/or new metastasis
timeFrame: 5 years
measure: Assessment of Metastasis
timeFrame: 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Nova Scotia Health Authority
name: Carman A Giacomantonio, MD
role: PRINCIPAL_INVESTIGATOR
References: