Uveal MelanomaPhase 1/2NCT02913417
Yttrium90, Ipilimumab, & Nivolumab for Uveal Melanoma With Liver Metastases
A Phase 1/2 study testing SIR-Spheres® Yttrium 90, ipilimumab and nivolumab in people with Uveal Melanoma and Hepatic Metastases, run by David Minor, MD at 3 sites in United States.
Trial summary
Reports to date show limited efficacy of immunotherapy for uveal melanoma. Recent experimental and clinical evidence suggests synergy between radiation therapy and immunotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma, Hepatic Metastases
- What is being tested?
- SIR-Spheres® Yttrium 90, ipilimumab and nivolumab
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- 10 Oct 2016to Jun 2023
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic diagnosis of metastatic uveal melanoma.
- Patients must have measurable disease as defined by RECIST (see Section 6).
- Patients must have liver metastasis
- Patients must have no more than one prior systemic therapeutic regimen. This includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment. This does not include any therapies given in the adjuvant setting. No prior anti-CTLA4 therapy. Prior anti PD-1 or anti-PDL-1 antibody therapy is acceptable.
- No concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids.
- Patients with prior selective internal radiation are candidates are eligible as long as they are candidates for repeat procedures and they have demonstrated progressive disease.
Show all 21Show fewer
- Age ≥ 18 years.
- No known infection with HIV. Due to the mechanism of action of ipilimumab, activity and side effects in an immune compromised patient are unknown.
- No active infection with Hepatitis B.
- No active infection with Hepatitis C.
- ECOG performance status 0 or 1.
- Women must not be pregnant or breast-feeding due to unknown effects of treatments on the unborn fetus. All women of childbearing potential must have a blood test within 72 hours prior to randomization to rule out pregnancy. Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. Sexually mature females who have not undergone a hysterectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months) are considered to be of childbearing potential. Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g.,vasectomy) should be considered to be of childbearing potential.
- Patients must have the following lab values obtained < 4 weeks prior to starting treatment:
- WBC ≥2000/uL
- ANC ≥1500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 8g/dL
- Creatinine ≤ 3.0 xULN
- AST and ALT < 2.5 x ULN
- Bilirubin ≤ 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
- Albumin ≥ 3g/dL
Who cannot join
- Patients are excluded if they have liver tumor volume > 50%
- Patients are excluded if they have active CNS metastases. Patients with history of CNS metastases must have MRI scans that show stability of brain metastases for 8 weeks.
- Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, or stage 1 or 2 cutaneous melanoma
- Patients are excluded if they have a history of autoimmune disease, as follows: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]). Patients with a history of Guillain-Barre Syndrome are excluded but myasthenia gravis or psoriasis is acceptable.
- Patients are excluded for any underlying medical or psychiatric condition which, in the opinion of the investigator, will make treatment hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
- Patients are excluded if they have a history of prior treatment with ipilimumab or CTLA-4 inhibitor.
- Patients are excluded if they have any concurrent medical condition requiring the use of systemic steroids (the use of inhaled or topical steroids is permitted).
- Patients are excluded if they have had prior hepatic arterial embolization therapy
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Chicago
Chicago, Illinois, 60637
Jefferson Medical College of Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
California Pacific Medical Center
San Francisco, California, 94115
About this study
Official title: A Feasibility Study of Sequential Hepatic Internal Radiation and Systemic Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastatic to Liver.
Reports to date show limited efficacy of immunotherapy for uveal melanoma. Recent experimental and clinical evidence suggests synergy between radiation therapy and immunotherapy. The investigators will explore this synergy with a feasibility study of 26 patients with uveal melanoma and hepatic metastases who will receive SirSpheres Yttrium-90 selective internal hepatic radiation followed by immunotherapy with the combination of ipilimumab and nivolumab.
Read the detailed description
Despite rapid improvements in the treatment of cutaneous melanoma, there has been little advance in therapy for uveal melanoma with hepatic metastases, an fatal orphan disease with no established therapy. Studies by Dr. Sato and others have described some activity for selective internal radiation with Yttrium90 microspheres (SIR-Spheres).There is limited activity as single agents for both the immunotherapy drugs ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). In cutaneous melanoma the combination of ipilimumab and nivolumab is clearly synergistic with improvement in response rates and progression-free survival over single agents; however this has yet to be established for uveal melanoma.
Recent experimental and clinical evidence suggests additional synergy between radiation therapy and immunotherapy. This synergy seems most evident when radiation is given through large fraction stereotactic treatments or brachytherapy. The investigators will explore this synergy with a feasibility study of 18 patients who will receive SirSpheres Yttrium-90 selective internal radiation given through the hepatic artery in two treatments followed by immunotherapy with the combination of ipilimumab and nivolumab. The immunotherapy will be given with the dose and schedule that has been established and FDA-approved for cutaneous melanoma. Because of the generally low toxicity of Yttrium-90 selective internal radiation therapy the investigators feel it can be given in full dosage prior to full dosage of immunotherapy.
- Conditions
- Uveal Melanoma, Hepatic Metastases
- Being tested
- SIR-Spheres® Yttrium 90, ipilimumab, nivolumab
- Keywords
- uveal melanoma, liver metastases
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SIR-Spheres® Yttrium 90Device
Patient treatment will consist of three parts: first, selective internal radiation with SIR-Spheres Yttrium-90 microspheres with dosage per package insert , reduced to give 35cGymax to normal liver; second, concurrent ipilimumab 1mg/kg and nivolumab 1mg/kg every 3 weeks for 4 doses (immunotherapy part 1); then maintenance nivolumab at 480 every 2 weeks (immunotherapy part 2) until progression or 3 years
ipilimumabDrug
Also called Yervoy
ipilimumab 1mg/kg every 3 weeks x 4
nivolumabDrug
Also called Opdivo
nivolumab 3mg/kg every 3 weeks x 4 then 480mg q 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| hepatic radiation followed by immunotherapy | Experimental | SIR-Spheres Yttrium 90 will be given by injection into the hepatic artery in two treatments, one for each lobe. 3-5 weeks later patients receive concurrent ipilimumab 1mg/kg q 3 wk x 4 and nivolumab 3mg/kg q 3 weeks x 4, all followed by nivolumab 240mg/kg q 2 weeks or 480 mg q 4 weeks until progression or 3 years Receives: Device: SIR-Spheres® Yttrium 90; Drug: ipilimumab; Drug: nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety and tolerability of sequential selective internal radiation with Yttrium90 followed by immunotherapy with ipilimumab and nivolumab.
Determine the safety and tolerability of sequential selective internal radiation with Y90 followed by immunotherapy with ipilimumab and nivolumab in patients with uveal melanoma metastatic to the liver. Endpoints are CTAE determined grade 3-5 toxicities.
Measured: 5 years
Secondary outcomes (4)
Preliminary clinical efficacy
co-endpoints for this measure will be RECIST response rate and PFS
Measured: 5 years
immunological changes
Changes in peripheral blood lymphocyte counts
Measured: 5 years
Correlation of tissue markers and response to immunotherapy
Study of archival tumor tissue for tumor mutations, PDL-1, PDL-2, others
Measured: 5 years
Explore relationship of response to immunotherapy with tumor melanin
Correlate response with tumor production of melanin assessed by tumor density on MRI scans
Measured: 5years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study start10 Oct 2016
- Primary completionJan 2022 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Uveal 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Minor, MD
- Sponsor type
- University, hospital or other
- Collaborators
- California Pacific Medical Center, Jefferson Medical College of Thomas Jefferson University, University of Chicago
- Responsible party
- Sponsor-investigator, David Minor, MD, California Pacific Medical Center Research Institute
- Investigators
- David R. Minor, M.D., Study chair, California Pacific Medical Center Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02913417
- Sponsor's protocol ID
- Uveal Melanoma IIP
- Status last verified
- Apr 2021
- First submitted
- 21 Sep 2016
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Minor DR, Kim KB, Tong RT, Wu MC, Kashani-Sabet M, Orloff M, Eschelman DJ, Gonsalves CF, Adamo RD, Anne PR, Luke JJ, Char D, Sato T. A Pilot Study of Hepatic Irradiation with Yttrium-90 Microspheres Followed by Immunotherapy with Ipilimumab and Nivolumab for Metastatic Uveal Melanoma. Cancer Biother Radiopharm. 2022 Feb;37(1):11-16. doi: 10.1089/cbr.2021.0366. Epub 2022 Jan 12.
PubMed 35021863
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Study of Sequential Hepatic Internal Radiation and Systemic Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastatic to Liver.
- ClinicalTrials.gov ID
- NCT02913417
- Acronym / sponsor ID
- Uveal Melanoma IIP
- Conditions
- Uveal Melanoma, Hepatic Metastases
- Keywords
- uveal melanoma, liver metastases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- David Minor, MDUniversity, hospital or other
- Collaborators
- California Pacific Medical Center, Jefferson Medical College of Thomas Jefferson University, University of Chicago
- Study start
- 10 Oct 2016
- Primary completion
- Jan 2022 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 23 Sep 2016 (estimated)
- 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.
Reports to date show limited efficacy of immunotherapy for uveal melanoma. Recent experimental and clinical evidence suggests synergy between radiation therapy and immunotherapy. The investigators will explore this synergy with a feasibility study of 26 patients with uveal melanoma and hepatic metastases who will receive SirSpheres Yttrium-90 selective internal hepatic radiation followed by immunotherapy with the combination of ipilimumab and nivolumab.
Detailed description
Despite rapid improvements in the treatment of cutaneous melanoma, there has been little advance in therapy for uveal melanoma with hepatic metastases, an fatal orphan disease with no established therapy. Studies by Dr. Sato and others have described some activity for selective internal radiation with Yttrium90 microspheres (SIR-Spheres).There is limited activity as single agents for both the immunotherapy drugs ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). In cutaneous melanoma the combination of ipilimumab and nivolumab is clearly synergistic with improvement in response rates and progression-free survival over single agents; however this has yet to be established for uveal melanoma.
Recent experimental and clinical evidence suggests additional synergy between radiation therapy and immunotherapy. This synergy seems most evident when radiation is given through large fraction stereotactic treatments or brachytherapy. The investigators will explore this synergy with a feasibility study of 18 patients who will receive SirSpheres Yttrium-90 selective internal radiation given through the hepatic artery in two treatments followed by immunotherapy with the combination of ipilimumab and nivolumab. The immunotherapy will be given with the dose and schedule that has been established and FDA-approved for cutaneous melanoma. Because of the generally low toxicity of Yttrium-90 selective internal radiation therapy the investigators feel it can be given in full dosage prior to full dosage of immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| hepatic radiation followed by immunotherapy | Experimental | Device: SIR-Spheres® Yttrium 90, Drug: ipilimumab, Drug: nivolumabSIR-Spheres Yttrium 90 will be given by injection into the hepatic artery in two treatments, one for each lobe. 3-5 weeks later patients receive concurrent ipilimumab 1mg/kg q 3 wk x 4 and nivolumab 3mg/kg q 3 weeks x 4, all followed by nivolumab 240mg/kg q 2 weeks or 480 mg q 4 weeks until progression or 3 years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologic diagnosis of metastatic uveal melanoma.
- Patients must have measurable disease as defined by RECIST (see Section 6).
- Patients must have liver metastasis
- Patients must have no more than one prior systemic therapeutic regimen. This includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment. This does not include any therapies given in the adjuvant setting. No prior anti-CTLA4 therapy. Prior anti PD-1 or anti-PDL-1 antibody therapy is acceptable.
- No concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids.
Key exclusion criteria (8 listed)
- Patients are excluded if they have liver tumor volume > 50%
- Patients are excluded if they have active CNS metastases. Patients with history of CNS metastases must have MRI scans that show stability of brain metastases for 8 weeks.
- Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, or stage 1 or 2 cutaneous melanoma
- Patients are excluded if they have a history of autoimmune disease, as follows: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]). Patients with a history of Guillain-Barre Syndrome are excluded but myasthenia gravis or psoriasis is acceptable.
- Patients are excluded for any underlying medical or psychiatric condition which, in the opinion of the investigator, will make treatment hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
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 |
|---|---|---|
| SIR-Spheres® Yttrium 90Patient treatment will consist of three parts: first, selective internal radiation with SIR-Spheres Yttrium-90 microspheres with dosage per package insert , reduced to give 35cGymax to normal liver; second, concurrent ipilimumab 1mg/kg and nivolumab 1mg/kg every 3 weeks for 4 doses (immunotherapy part 1); then maintenance nivolumab at 480 every 2 weeks (immunotherapy part 2) until progression or 3 years | Device | hepatic radiation followed by immunotherapy |
| ipilimumabAlso: Yervoyipilimumab 1mg/kg every 3 weeks x 4 | Drug | hepatic radiation followed by immunotherapy |
| nivolumabAlso: Opdivonivolumab 3mg/kg every 3 weeks x 4 then 480mg q 4 weeks | Drug | hepatic radiation followed by immunotherapy |
Primary outcome
safety and tolerability of sequential selective internal radiation with Yttrium90 followed by immunotherapy with ipilimumab and nivolumab.
Time frame: 5 years
Determine the safety and tolerability of sequential selective internal radiation with Y90 followed by immunotherapy with ipilimumab and nivolumab in patients with uveal melanoma metastatic to the liver. Endpoints are CTAE determined grade 3-5 toxicities.
4 secondary outcomes
Preliminary clinical efficacy
Time frame: 5 years
immunological changes
Time frame: 5 years
Correlation of tissue markers and response to immunotherapy
Time frame: 5 years
Explore relationship of response to immunotherapy with tumor melanin
Time frame: 5years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Derived from this study: PubMed 35021863Minor DR, Kim KB, Tong RT, Wu MC, Kashani-Sabet M, Orloff M, Eschelman DJ, Gonsalves CF, Adamo RD, Anne PR, Luke JJ, Char D, Sato T. A Pilot Study of Hepatic Irradiation with Yttrium-90 Microspheres Followed by Immunotherapy with Ipilimumab and Nivolumab for Metastatic Uveal Melanoma. Cancer Biother Radiopharm. 2022 Feb;37(1):11-16. doi: 10.1089/cbr.2021.0366. Epub 2022 Jan 12.
- 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.
David R. Minor, M.D. study chair
California Pacific Medical Center Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SIR-Spheres® Yttrium 90, ipilimumab and nivolumab in people with Uveal Melanoma and Hepatic Metastases, run by David Minor, MD at 3 sites 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 21 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
safety and tolerability of sequential selective internal radiation with Yttrium90 followed by immunotherapy with ipilimumab and nivolumab. (time frame: 5 years). 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 NCT02913417, which also lists 1 linked publication.
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 19 Apr 2021.