Cutaneous Metastatic MelanomaPhase 2/3NCT03928275
The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma
A Phase 2/3 study testing Interleukin-2 and Combination therapy Interleukin-2 and Bacillus Calmette Guerin in people with Cutaneous Metastatic Melanoma, run by Carman Giacomantonio.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cutaneous Metastatic Melanoma
- What is being tested?
- Interleukin-2 and Combination therapy Interleukin-2 and Bacillus Calmette Guerin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2021to 1 Sep 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with cutaneous metastatic melanoma.
- Has 4 or more melanoma lesions.
- Between18 and 80 years of age.
Who cannot join
- Immunocompromized.
- Receiving immuno-therapy for other diagnosis.
- Inflammatory disease.
- Autoimmune disease.
- Pregnant
- HIV
- Test positive for TB
About this study
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).
Read the 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.
- Conditions
- Cutaneous Metastatic Melanoma
- Being tested
- Interleukin-2, Combination therapy Interleukin-2 and Bacillus Calmette Guerin
- Keywords
- Interleukin-2, Bacillus Calmette Guerin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interleukin-2Biological
Also called Proleukin (Aldesleukin)
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.
Combination therapy Interleukin-2 and Bacillus Calmette GuerinBiological
Also called BCG, strain TICE (OncoTICE) and Proleukin (Aldesleukin)
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).
| Study group | Role | What they receive |
|---|---|---|
| Intralesional IL-2 Treatment | Experimental | CMM patients will received 4 treatments of intralesional Interleukin-2 two weeks apart over an eight week period. Receives: Biological: Interleukin-2 |
| Combination therapy: Intralesional IL-2 and BCG Treatment | Experimental | CMM patients will receive 4 treatments of combination therapy intralesional Interleukin-2 and Bacillus Calmette Guerin two weeks apart over an eight week period. Receives: Biological: Combination therapy Interleukin-2 and Bacillus Calmette Guerin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of CMM participants that respond to IL-2 compared to the number of participants that respond to IL-2 and BCG.
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.
Measured: 5 years
Secondary outcomes (5)
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.
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.
Measured: 5 years
Assessment of overall survival in stage one treatment
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.
Measured: 5 years
Assessment of overall survival in stage two treatment
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.
Measured: 5 years
Assessment of Disease Progression Within Stage of Disease: Number of stable and/or new 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 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.
Measured: 5 years
Assessment of Metastasis
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.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study start1 Dec 2021 (estimated)
- Primary completion1 Sep 2022
- Study completion1 Sep 2022
Why it stopped: Withdrawn prematurely.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carman Giacomantonio
- Sponsor type
- University, hospital or other
- Collaborators
- Nova Scotia Health Authority
- Responsible party
- Sponsor-investigator, Carman Giacomantonio, Nova Scotia Health Authority
- Investigators
- Carman A Giacomantonio, MD, Principal investigator, Nova Scotia Health Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03928275
- Sponsor's protocol ID
- 14549
- Status last verified
- Feb 2023
- First submitted
- 11 Apr 2019
- Last updated
- 14 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT03928275
- Acronym / sponsor ID
- 14549
- Conditions
- Cutaneous Metastatic Melanoma
- Keywords
- Interleukin-2, Bacillus Calmette Guerin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn prematurely.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Carman GiacomantonioUniversity, hospital or other
- Collaborators
- Nova Scotia Health Authority
- Study start
- 1 Dec 2021 (estimated)
- Primary completion
- 1 Sep 2022 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 26 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Intralesional IL-2 Treatment | Experimental | Biological: Interleukin-2CMM patients will received 4 treatments of intralesional Interleukin-2 two weeks apart over an eight week period. |
| Combination therapy: Intralesional IL-2 and BCG Treatment | Experimental | Biological: Combination therapy Interleukin-2 and Bacillus Calmette GuerinCMM patients will receive 4 treatments of combination therapy intralesional Interleukin-2 and Bacillus Calmette Guerin two weeks apart over an eight week period. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patient with cutaneous metastatic melanoma.
- Has 4 or more melanoma lesions.
- Between18 and 80 years of age.
Key exclusion criteria (7 listed)
- Immunocompromized.
- Receiving immuno-therapy for other diagnosis.
- Inflammatory disease.
- Autoimmune disease.
- Pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interleukin-2Also: Proleukin (Aldesleukin)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. | Biological | Intralesional IL-2 Treatment |
| Combination therapy Interleukin-2 and Bacillus Calmette GuerinAlso: BCG, strain TICE (OncoTICE) and Proleukin (Aldesleukin)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). | Biological | Combination therapy: Intralesional IL-2 and BCG Treatment |
Primary outcome
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.
5 secondary outcomes
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
Assessment of overall survival in stage one treatment
Time frame: 5 years
Assessment of overall survival in stage two treatment
Time frame: 5 years
Assessment of Disease Progression Within Stage of Disease: Number of stable and/or new metastasis
Time frame: 5 years
Assessment of Metastasis
Time frame: 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carman A Giacomantonio, MD principal investigator
Nova Scotia Health Authority
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Interleukin-2 and Combination therapy Interleukin-2 and Bacillus Calmette Guerin in people with Cutaneous Metastatic Melanoma, run by Carman Giacomantonio.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2023.