MelanomaPhase 2NCT02796352
A Phase II Study of High Dose Bolus IL2 in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy: Efficacy and Biomarker Study
A Phase 2 study testing High dose bolus interleukin-2 (HD IL2) in people with Melanoma, run by Ahmad Tarhini at 1 site in United States.
Trial summary
This study is for patients with advanced stage III or stage IV melanoma not adequately treated by surgery who have progressed after treatment with nivolumab or pembrolizumab. The purpose of this study is to see if giving high dose interleukin-2 (IL-2) after progression on nivolumab or pembrolizumab is effective in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- High dose bolus interleukin-2 (HD IL2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed metastatic melanoma. This includes American Joint Committee on Cancer (AJCC) stage IV or advanced/inoperable stage III. This also includes patients with a history of lower stage melanoma and subsequent recurrent metastatic disease that is either locally/regionally advanced/inoperable disease or distant metastases.
- Patients must have measurable disease, according to RECIST version 1.1
- Patients must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to enrollment. If known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study.
- A patient must have previously received anti-PD1 immunotherapy (nivolumab or pembrolizumab) and later experienced disease progression, within 3 months of registration on this study.
- Patients must not have received systemic therapy or radiotherapy within the preceding 3 weeks. Patients must have recovered from adverse events from previous therapy by the time registration.
- Patients must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery, and be free of significant detectable infection prior to registration.
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- For patients who have received prior anti-CTLA4 monoclonal antibody therapy (ipilimumab or tremelimumab), there is a risk of bowel perforation with IL-2 therapy. Therefore, for these patients if they have a history of colitis or diarrhea during anti-CTLA4 monoclonal antibody therapy, it is recommended that they have a formal evaluation by a gastroenterologist and a colonoscopy/endoscopy should be considered to demonstrate the absence of active bowel inflammation before initiating IL-2 therapy on this protocol.
- Life expectancy of greater than 3 months in the opinion of the investigator.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >/=70%)
- Patients must have normal organ and marrow function as defined in the clinical trial protocol.
- Patients on full-dose anticoagulants (e.g., warfarin) with prothrombin time (PT)/ international normalized ratio (INR) >1.5 are eligible provided that both of the following criteria are met: (a) The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin. (b) The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
- Pulmonary: forced expiratory volume at one second (FEV1) > 2.0 liters or > 75% of predicted for height and age. Pulmonary function tests (PFTs) are required for patients over 50 years old or with significant pulmonary or smoking history.
- Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias, or unstable angina. Patients who are over 40 years old or have had previous myocardial infarction greater than 6 months prior to study entry or have significant cardiac family history (CAD or serious arrhythmias) will be required to have a negative or low probability cardiac stress test (for example, thallium stress test, stress multigated acquisition (MUGA), stress echo or exercise stress test) for cardiac ischemia within 8 weeks prior to registration.
- Central Nervous System (CNS): No history of cerebrovascular accident or transient ischemic attacks within the past 6 months from registration.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after completion of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Women should not be lactating and, if of childbearing age, should have a negative pregnancy test (b-HCG test; serum or urine, minimum sensitivity 25 IU/L or equivalent units of b-HCG) within two week of registration in the study.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had systemic therapy for melanoma or radiotherapy within 3 weeks prior to registering on the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. Patients with a history of endocrinopathies (e.g. hypothyroidism, adrenal insufficiency, hypopituitarism) are eligible if they are stable on hormone replacement therapy.
- Patients may not be receiving any other investigational agents.
- Patients with active brain metastases should be excluded from this clinical trial except as noted above.
- Patients with clinically significant cardiovascular or cerebrovascular disease:
- history of cerebrovascular accident or transient ischemic attack within past 6 months from registration.
- myocardial infarction, coronary artery bypass grafting (CABG) or unstable angina within the past 6 Months from registration.
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- New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months from registration.
- clinically significant peripheral vascular disease within past 6 months from registration.
- PT INR >1.5 unless the patient is on full-dose warfarin.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who have other current malignancies are not eligible. Patients with other malignancies are eligible if they have been continuously disease free for > 2 years prior to the time of registration. Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are eligible. Patients with prior history of basal or squamous skin cancer are eligible. Patients who have had multiple primary melanomas are eligible.
- Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids or steroid inhalers. If a patient had been taking steroids, at least 2 weeks must have passed since the last dose. Patients stable on physiologic replacement doses of steroids or other forms of hormone replacement therapy are eligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center- Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
This study is for patients with advanced stage III or stage IV melanoma not adequately treated by surgery who have progressed after treatment with nivolumab or pembrolizumab. The purpose of this study is to see if giving high dose interleukin-2 (IL-2) after progression on nivolumab or pembrolizumab is effective in treating metastatic melanoma. This study is also being done to look at the severity of side effects of IL-2 in patients.
IL-2 is approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma.
Read the detailed description
This is a phase II study of high dose bolus interleukin-2 (HD IL2) in patients with advanced inoperable stage III or stage IV melanoma who have prior anti-PD1 immunotherapy.
Each course consists of 2 cycles of HD IL2 as follows: high-dose IL2 at 600,000 IU/kg is given intravenously (IV) every 8 hours for up to 14 doses (one cycle), followed by a rest period of 1-2 weeks and readmission for a second HD IL2 cycle for up to 14 doses (second cycle).
The planned treatment consists of 3 courses (6 cycles) of HD IL-2. Response assessment will occur at the end of each course of therapy and patients without evidence of disease progression (Response Evaluation Criteria in Solid Tumors, RECIST, version 1.1) or limiting toxicities will be offered additional courses of treatment of HD IL2 for a maximum of 3 courses.
- Conditions
- Melanoma
- Being tested
- High dose bolus interleukin-2 (HD IL2)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High dose bolus interleukin-2 (HD IL2)Drug
Each course consists of 2 cycles of HD IL2 as follows: high-dose IL2 at 600,000 IU/kg is given intravenously (IV) every 8 hours for up to 14 doses (one cycle), followed by a rest period of 1-2 weeks and readmission for a second HD IL2 cycle for up to 14 doses (second cycle).
The planned treatment consists of 3 courses (6 cycles) of HD IL-2.
| Study group | Role | What they receive |
|---|---|---|
| High dose bolus interleukin-2 (HD IL2) | Experimental | Not described Receives: Drug: High dose bolus interleukin-2 (HD IL2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Percentage of complete responses (CR) plus partial responses (PR), based upon Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
Measured: Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled (21 months)
Secondary outcomes (3)
Progression Free Survival (PFS)
Number of months of survival without disease progression from start of protocol therapy until objective tumor progression or death, per RECIST v1.1
Measured: Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled, plus 5 years of follow-up (6 years, 9 months)
Overall Survival (OS)
Number of months from start of protocol therapy until death from any cause.
Measured: Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled, plus 5 years of follow-up (6 years, 9 months)
HD IL2 Levels
Levels of HD IL2 biomarker in the blood of patients that received at least course 1 of therapy, and have had their disease re-evaluated will be considered evaluable for response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) version 1.1
Measured: Up to 21 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2016 (estimated)
- Study startSep 2016
- Primary completion16 Feb 2017
- Study completionApr 2017
Why it stopped: Slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ahmad Tarhini
- Sponsor type
- University, hospital or other
- Collaborators
- Prometheus Laboratories
- Responsible party
- Sponsor-investigator, Ahmad Tarhini, University of Pittsburgh
- Investigators
- Ahmad Tarhini, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02796352
- Sponsor's protocol ID
- 15-114
- Status last verified
- Mar 2018
- First submitted
- 6 Jun 2016
- Last updated
- 20 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of High Dose Bolus IL2 in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy: Efficacy and Biomarker Study
- ClinicalTrials.gov ID
- NCT02796352
- Acronym / sponsor ID
- 15-114
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Ahmad TarhiniUniversity, hospital or other
- Collaborators
- Prometheus Laboratories
- Study start
- Sep 2016 (actual)
- Primary completion
- 16 Feb 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 10 Jun 2016 (estimated)
- Results
- Posted 20 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is for patients with advanced stage III or stage IV melanoma not adequately treated by surgery who have progressed after treatment with nivolumab or pembrolizumab. The purpose of this study is to see if giving high dose interleukin-2 (IL-2) after progression on nivolumab or pembrolizumab is effective in treating metastatic melanoma. This study is also being done to look at the severity of side effects of IL-2 in patients.
IL-2 is approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma.
Detailed description
This is a phase II study of high dose bolus interleukin-2 (HD IL2) in patients with advanced inoperable stage III or stage IV melanoma who have prior anti-PD1 immunotherapy.
Each course consists of 2 cycles of HD IL2 as follows: high-dose IL2 at 600,000 IU/kg is given intravenously (IV) every 8 hours for up to 14 doses (one cycle), followed by a rest period of 1-2 weeks and readmission for a second HD IL2 cycle for up to 14 doses (second cycle).
The planned treatment consists of 3 courses (6 cycles) of HD IL-2. Response assessment will occur at the end of each course of therapy and patients without evidence of disease progression (Response Evaluation Criteria in Solid Tumors, RECIST, version 1.1) or limiting toxicities will be offered additional courses of treatment of HD IL2 for a maximum of 3 courses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High dose bolus interleukin-2 (HD IL2) | Experimental | Drug: High dose bolus interleukin-2 (HD IL2) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have histologically or cytologically confirmed metastatic melanoma. This includes American Joint Committee on Cancer (AJCC) stage IV or advanced/inoperable stage III. This also includes patients with a history of lower stage melanoma and subsequent recurrent metastatic disease that is either locally/regionally advanced/inoperable disease or distant metastases.
- Patients must have measurable disease, according to RECIST version 1.1
- Patients must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to enrollment. If known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study.
- A patient must have previously received anti-PD1 immunotherapy (nivolumab or pembrolizumab) and later experienced disease progression, within 3 months of registration on this study.
- Patients must not have received systemic therapy or radiotherapy within the preceding 3 weeks. Patients must have recovered from adverse events from previous therapy by the time registration.
Key exclusion criteria (12 listed)
- Patients who have had systemic therapy for melanoma or radiotherapy within 3 weeks prior to registering on the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. Patients with a history of endocrinopathies (e.g. hypothyroidism, adrenal insufficiency, hypopituitarism) are eligible if they are stable on hormone replacement therapy.
- Patients may not be receiving any other investigational agents.
- Patients with active brain metastases should be excluded from this clinical trial except as noted above.
- Patients with clinically significant cardiovascular or cerebrovascular disease:
- PT INR >1.5 unless the patient is on full-dose warfarin.
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 |
|---|---|---|
| High dose bolus interleukin-2 (HD IL2)Each course consists of 2 cycles of HD IL2 as follows: high-dose IL2 at 600,000 IU/kg is given intravenously (IV) every 8 hours for up to 14 doses (one cycle), followed by a rest period of 1-2 weeks and readmission for a second HD IL2 cycle for up to 14 doses (second cycle). The planned treatment consists of 3 courses (6 cycles) of HD IL-2. | Drug | High dose bolus interleukin-2 (HD IL2) |
Primary outcome
Response Rate
Time frame: Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled (21 months)
Percentage of complete responses (CR) plus partial responses (PR), based upon Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled, plus 5 years of follow-up (6 years, 9 months)
Overall Survival (OS)
Time frame: Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled, plus 5 years of follow-up (6 years, 9 months)
HD IL2 Levels
Time frame: Up to 21 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ahmad Tarhini, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High dose bolus interleukin-2 (HD IL2) in people with Melanoma, run by Ahmad Tarhini at 1 site in United States.
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 17 inclusion and 12 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: stopped early, as of the sponsor's last update on 20 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Response Rate (time frame: Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled (21 months)). 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 20 Apr 2018.