MelanomaPhase 2NCT00590824
Pilot hu14.18-IL2 in Resectable Recurrent Stage III or Stage IV Melanoma
A Phase 2 study testing hu14.18-IL2 in people with Melanoma, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
Evaluate the antitumor activity of hu14.18-IL2 in the minimal residual disease setting. Evaluate the time to recurrence and overall survival of patients treated with hu14.18-IL2. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- hu14.18-IL2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2007to 20 Sep 2018
- 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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects must have recurrent stage III (i.e., recurrent regional metastasis), or stage IV (i.e., any distant metastasis) melanoma for which surgical resection would be clinically recommended, with biopsy proven (current or previous) Stage III or Stage IV disease. Any biopsies obtained to demonstrate recurrent regional metastasis or distant metastasis must be considered clinically appropriate for clinical management and must not be performed solely for meeting eligibility criteria. In addition, subjects must have disease that has not yet been completely excised.
- Patients must have disease which involves 3 or fewer sites. A nodal basin recurrence will be scored as one site, even if multiple nodes are positive. "Clustered" subcutaneous and/or cutaneous lesions that can be removed in a single surgical excision will be scored as one site, even if multiple subcutaneous and/or cutaneous lesions are present.
- The subjects' disease is determined to be completely resectable with uninvolved margins using standard surgical guidelines based on physical exam and radiographic imaging (MRI or CT of the head, and CT or MRI of the chest, abdomen and pelvis).
- Subjects must have one of the following: a) Stage III melanoma with recurrence after prior surgery, with or without subsequent adjuvant systemic (standard or experimental) and/or radiotherapy management Or b) Stage IV melanoma (cutaneous, ocular, mucosal, or unknown primary)
- Subjects must be 18 years old or older OR if they are 15 years old or greater, considered to be mature minors, able to give adult informed consent (with parental co-signature), meet all other eligibility criteria, and also weigh at least 45 kg.. Subjects must weigh at least 45 kg in order to safely provide sufficient blood for monitoring studies (see section 7.7 for details).
- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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- Subjects must have adequate bone marrow, liver, and renal function.
- Subjects with one or more of the following cardiac risk factors must complete a stress radionuclide scan with no evidence of myocardial ischemia or heart failure: (a) a history of cardiac disease, (b) age greater than 65 years old, (c) any clinically significant abnormality found on ECG (required at baseline), or (d) significant risk factors for coronary artery disease (history of significant dyslipidemia; any treatment for dyslipidemia; or two first degree relatives with a documented myocardial infarction prior to age 55).
- Subjects with significant history of pulmonary disease, shortness of breath at rest, or known Chronic Obstructive Pulmonary Disease (COPD) must have pulmonary function tests within 35% of normal age-predicted values.
- Subjects must be willing and able to provide informed written consent prior to any study-related procedures.
- Subjects must have no immediate requirements for palliative chemotherapy, palliative radiotherapy, or palliative hormonal therapy.
- Subjects must be willing and able to discontinue antihypertensive medications if advised to do so for days of hu14.18-IL2 infusion.
- Subjects must have slides available from stage III or stage IV melanoma. Paraffin blocks are preferable, but at a minimum, slides documenting melanoma by biopsy (including fine needle cytology) must be available for pathology review, and potential restaining/staining (see Section 7.4, Surgical Pathology Guidelines). Prior histologic demonstration of metastatic melanoma (either stage III or Stage IV) may be utilized if a repeat biopsy is not clinically needed to to establish eligibility.
Who cannot join
- Subjects are ineligible if they have received monoclonal antibodies (mAb) during biologic therapy, tumor imaging, purging of autologous marrow/stem cells for re-infusion or for any other reason unless serological testing is performed. If the absence of detectable antibody (over background) to hu14.18 is documented, the subject is eligible for the study.
- Subjects treated with IL2 in the past that developed intolerable (Grade 4) IL2-related side effects are not eligible.
- Subjects who have received any (standard or experimental) systemic therapy for stage IV disease are not eligible.
- Women of childbearing potential will be excluded if they are pregnant, nursing, or not using effective contraception during the treatment period.
- Subjects with symptoms of ischemic cardiac disease, congestive heart failure, myocardial infarct within the immediate preceding 6 months and/or uncontrolled cardiac rhythm disturbance are ineligible.
- Subjects with significant psychiatric disabilities or seizure disorders are ineligible.
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- Subjects who have had major surgery within the past 3 weeks are ineligible.
- Subjects with clinically detectable pleural effusions or ascites are ineligible.
- Subjects with organ allografts are ineligible.
- Subjects who require or are likely to require corticosteroid or other immunosuppressive drugs or have used them within 2 weeks of registration are ineligible.
- Subjects with significant intercurrent illnesses are ineligible.
- Subjects with active infections or active peptic ulcer unless these conditions are corrected or controlled are ineligible.
- Subjects with brain metastases, whether active or inactive, are ineligible. A head MRI or head CT scan will be required at baseline to rule out silent metastases.
- Subjects with active second malignancy other than non-melanoma skin cancer are ineligible. Patients will be considered eligible if they have been continuously disease free for > 5 years prior to the time of enrollment.
- Subjects who are infected with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBs Ag) carrier state or with clinical evidence of hepatitis are ineligible. Treatment may be initiated before laboratory confirmation of HIV and HBs Ag negativity, but will be stopped if results are positive.
- Subjects with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade > 2) are ineligible.
- Subjects with a known hypersensitivity to the study drug, Tween-80® or to human immunoglobulin are ineligible.
- Patients with a known history of diabetes mellitus that has required systemic therapy within the past 3 months (either oral hypoglycemic agents or insulin) will be excluded, as treatment with hu14.18-IL2 may alter blood glucose levels.
- Subjects with a legal incapacity or limited legal capacity are ineligible.
- Subjects with bone metastases are ineligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792
About this study
Official title: A Pilot Trial of HU14.18-IL2 (EMD273063) in Subjects With Completely Resectable Recurrent Stage III or Stage IV Melanoma
Evaluate the antitumor activity of hu14.18-IL2 in the minimal residual disease setting. Evaluate the time to recurrence and overall survival of patients treated with hu14.18-IL2.
- Conditions
- Melanoma
- Being tested
- hu14.18-IL2
- Keywords
- Melanoma, hu14.18-IL2
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hu14.18-IL2Drug
6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
hu14.18-IL2Drug
Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Hu14.18-IL2 -->Resection-->Hu14.18-IL2 Receives: Drug: hu14.18-IL2 |
| B | Experimental | Resection -->Hu14.18-IL2-->Hu14.18-IL2 Receives: Drug: hu14.18-IL2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ganglioside Expressed by Tumor Cells (GD2)
Histological analysis of anti-tumor activity is a primary endpoint. This is measured after surgical resection via staining to indicate GD2 expression. The GD2 results were summarized in terms of positive (GD2 expression high or low/moderate) and negative (GD2 expression undetectable).
Measured: up to 1 week
Recurrence Free Survival (RFS)
RFS was defined as the number of days from the day of evaluation following course 2 of immunocytokine treatment to the day the subject experienced an event of recurrence or death, whichever occurred first. Participants who did not experience an event of recurrence or death at the time of analysis were censored at the date of the last evaluation for recurrence.
Measured: up to 24 months
Overall Survival (OS)
OS was defined as the number of days from randomization to the date of the participant's death. Participants who did not experience an event of death at the time of analysis were censored at the date of the last follow-up.
Measured: up to 24 months
Secondary outcomes (5)
C-Reactive Protein (CRP)
CRP measured at baseline, cycle 1 day 3, and cycle 2 day 1.
Measured: up to 29 days
Lymphocyte Count
Lymphocyte count measured at baseline, cycle 1 day 3, cycle 1 day 8, and cycle 2 day 1
Measured: up to 29 days
Anti-Idiotypic Antibodies
Detection of anti-idiotypic will be performed on participants' serum obtained approximately 10 minutes prior to initiation of treatment, and serum samples on Days 3, 4, 8, and 29/1 of 3 cycles.
Measured: up to 12 weeks
Anti-Fc-IL2 Antibodies
Detection of anti-FcIL2 will be performed on participants' serum obtained approximately 10 minutes prior to initiation of treatment, and serum samples on Days 3, 4, 8, and 29/1, for 3 cycles
Measured: up to 12 weeks
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Soluble IL2 receptor α levels will be performed on participants approximately 10 minutes prior to initiation of treatment, and serum samples on Days 3, 4, 8, and 29/1.
Measured: up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2008 (estimated)
- Study start17 Dec 2007
- Primary completion20 Sep 2018
- Study completion20 Sep 2018
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), EMD Serono
- Responsible party
- Sponsor
- Investigators
- Paul M Sondel, MD, PhD, Principal investigator, University of Wisconsin, MadisonMark R Albertini, MD, Study chair, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00590824
- Sponsor's protocol ID
- H-2007-0087
- Other IDs
- CO05601, 2013-1224, NCI-2009-00276, A536755, SMPH/PEDIATRICS/PEDIATRICS, R01CA032685
- Status last verified
- Nov 2019
- First submitted
- 19 Dec 2007
- Last updated
- 21 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Albertini MR, Yang RK, Ranheim EA, Hank JA, Zuleger CL, Weber S, Neuman H, Hartig G, Weigel T, Mahvi D, Henry MB, Quale R, McFarland T, Gan J, Carmichael L, Kim K, Loibner H, Gillies SD, Sondel PM. Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma. Cancer Immunol Immunother. 2018 Oct;67(10):1647-1658. doi: 10.1007/s00262-018-2223-z. Epub 2018 Aug 3.
PubMed 30073390Yang RK, Kuznetsov IB, Ranheim EA, Wei JS, Sindiri S, Gryder BE, Gangalapudi V, Song YK, Patel V, Hank JA, Zuleger C, Erbe AK, Morris ZS, Quale R, Kim K, Albertini MR, Khan J, Sondel PM. Outcome-Related Signatures Identified by Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated after Starting Hu14.18-IL2. Clin Cancer Res. 2020 Jul 1;26(13):3296-3306. doi: 10.1158/1078-0432.CCR-19-3294. Epub 2020 Mar 9.
PubMed 32152202
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of HU14.18-IL2 (EMD273063) in Subjects With Completely Resectable Recurrent Stage III or Stage IV Melanoma
- ClinicalTrials.gov ID
- NCT00590824
- Acronym / sponsor ID
- H-2007-0087
- Conditions
- Melanoma
- Keywords
- Melanoma, hu14.18-IL2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), EMD Serono
- Study start
- 17 Dec 2007 (actual)
- Primary completion
- 20 Sep 2018 (actual)
- Study completion
- 20 Sep 2018 (actual)
- First posted
- 11 Jan 2008 (estimated)
- Results
- Posted 22 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate the antitumor activity of hu14.18-IL2 in the minimal residual disease setting. Evaluate the time to recurrence and overall survival of patients treated with hu14.18-IL2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: hu14.18-IL2Hu14.18-IL2 -->Resection-->Hu14.18-IL2 |
| B | Experimental | Drug: hu14.18-IL2Resection -->Hu14.18-IL2-->Hu14.18-IL2 |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Subjects must have recurrent stage III (i.e., recurrent regional metastasis), or stage IV (i.e., any distant metastasis) melanoma for which surgical resection would be clinically recommended, with biopsy proven (current or previous) Stage III or Stage IV disease. Any biopsies obtained to demonstrate recurrent regional metastasis or distant metastasis must be considered clinically appropriate for clinical management and must not be performed solely for meeting eligibility criteria. In addition, subjects must have disease that has not yet been completely excised.
- Patients must have disease which involves 3 or fewer sites. A nodal basin recurrence will be scored as one site, even if multiple nodes are positive. "Clustered" subcutaneous and/or cutaneous lesions that can be removed in a single surgical excision will be scored as one site, even if multiple subcutaneous and/or cutaneous lesions are present.
- The subjects' disease is determined to be completely resectable with uninvolved margins using standard surgical guidelines based on physical exam and radiographic imaging (MRI or CT of the head, and CT or MRI of the chest, abdomen and pelvis).
- Subjects must have one of the following: a) Stage III melanoma with recurrence after prior surgery, with or without subsequent adjuvant systemic (standard or experimental) and/or radiotherapy management Or b) Stage IV melanoma (cutaneous, ocular, mucosal, or unknown primary)
- Subjects must be 18 years old or older OR if they are 15 years old or greater, considered to be mature minors, able to give adult informed consent (with parental co-signature), meet all other eligibility criteria, and also weigh at least 45 kg.. Subjects must weigh at least 45 kg in order to safely provide sufficient blood for monitoring studies (see section 7.7 for details).
Key exclusion criteria (20 listed)
- Subjects are ineligible if they have received monoclonal antibodies (mAb) during biologic therapy, tumor imaging, purging of autologous marrow/stem cells for re-infusion or for any other reason unless serological testing is performed. If the absence of detectable antibody (over background) to hu14.18 is documented, the subject is eligible for the study.
- Subjects treated with IL2 in the past that developed intolerable (Grade 4) IL2-related side effects are not eligible.
- Subjects who have received any (standard or experimental) systemic therapy for stage IV disease are not eligible.
- Women of childbearing potential will be excluded if they are pregnant, nursing, or not using effective contraception during the treatment period.
- Subjects with symptoms of ischemic cardiac disease, congestive heart failure, myocardial infarct within the immediate preceding 6 months and/or uncontrolled cardiac rhythm disturbance are ineligible.
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 |
|---|---|---|
| hu14.18-IL26 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2 | Drug | A |
| hu14.18-IL2Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course | Drug | B |
Primary outcome
Ganglioside Expressed by Tumor Cells (GD2)
Time frame: up to 1 week
Histological analysis of anti-tumor activity is a primary endpoint. This is measured after surgical resection via staining to indicate GD2 expression. The GD2 results were summarized in terms of positive (GD2 expression high or low/moderate) and negative (GD2 expression undetectable).
Recurrence Free Survival (RFS)
Time frame: up to 24 months
RFS was defined as the number of days from the day of evaluation following course 2 of immunocytokine treatment to the day the subject experienced an event of recurrence or death, whichever occurred first. Participants who did not experience an event of recurrence or death at the time of analysis were censored at the date of the last evaluation for recurrence.
Overall Survival (OS)
Time frame: up to 24 months
OS was defined as the number of days from randomization to the date of the participant's death. Participants who did not experience an event of death at the time of analysis were censored at the date of the last follow-up.
5 secondary outcomes
C-Reactive Protein (CRP)
Time frame: up to 29 days
Lymphocyte Count
Time frame: up to 29 days
Anti-Idiotypic Antibodies
Time frame: up to 12 weeks
Anti-Fc-IL2 Antibodies
Time frame: up to 12 weeks
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Time frame: up to 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30073390Albertini MR, Yang RK, Ranheim EA, Hank JA, Zuleger CL, Weber S, Neuman H, Hartig G, Weigel T, Mahvi D, Henry MB, Quale R, McFarland T, Gan J, Carmichael L, Kim K, Loibner H, Gillies SD, Sondel PM. Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma. Cancer Immunol Immunother. 2018 Oct;67(10):1647-1658. doi: 10.1007/s00262-018-2223-z. Epub 2018 Aug 3.
- Derived from this study: PubMed 32152202Yang RK, Kuznetsov IB, Ranheim EA, Wei JS, Sindiri S, Gryder BE, Gangalapudi V, Song YK, Patel V, Hank JA, Zuleger C, Erbe AK, Morris ZS, Quale R, Kim K, Albertini MR, Khan J, Sondel PM. Outcome-Related Signatures Identified by Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated after Starting Hu14.18-IL2. Clin Cancer Res. 2020 Jul 1;26(13):3296-3306. doi: 10.1158/1078-0432.CCR-19-3294. Epub 2020 Mar 9.
- University of Wisconsin Carbone Cancer CenterLink provided by the sponsor.
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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.
Paul M Sondel, MD, PhD principal investigator
University of Wisconsin, Madison
Mark R Albertini, MD study chair
University of Wisconsin, Madison
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 hu14.18-IL2 in people with Melanoma, run by University of Wisconsin, Madison 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 13 inclusion and 20 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: finished, as of the sponsor's last update on 21 Nov 2019. 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 22 Oct 2019). 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?
Ganglioside Expressed by Tumor Cells (GD2) (time frame: up to 1 week). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00590824, which also lists 2 linked publications.
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 21 Nov 2019.