Clinical Trials /

Yttrium90, Ipilimumab, & Nivolumab for Uveal Melanoma With Liver Metastases

NCT02913417

Description:

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.

Related Conditions:
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Yttrium90, Ipilimumab, & Nivolumab for Uveal Melanoma With Liver Metastases
  • Official Title: A Feasibility Study of Sequential Hepatic Internal Radiation and Systemic Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastatic to Liver.

Clinical Trial IDs

  • ORG STUDY ID: Uveal Melanoma IIP
  • NCT ID: NCT02913417

Conditions

  • Uveal Melanoma
  • Hepatic Metastases

Interventions

DrugSynonymsArms
ipilimumabhepatic radiation followed by immunotherapy
nivolumabhepatic radiation followed by immunotherapy

Purpose

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 18 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.
    

Trial Arms

NameTypeDescriptionInterventions
hepatic radiation followed by immunotherapyExperimentalSIR-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 3mg/kg q 3 wk x 4 and nivolumab 1mg/kg q 3 weeks x 4, all followed by nivolumab 3mg/kg q 2 weeks until progression or 3 years
  • ipilimumab
  • nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Histologic diagnosis of metastatic uveal melanoma.

          2. Patients must have measurable disease as defined by RECIST (see Section 6).

          3. Patients must have liver metastasis

          4. 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.

          5. 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.

          6. 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.

          7. Age ≥ 18 years.

          8. No known infection with HIV. Due to the mechanism of action of ipilimumab, activity
             and side effects in an immune compromised patient are unknown.

          9. No active infection with Hepatitis B.

         10. No active infection with Hepatitis C.

         11. ECOG performance status 0 or 1.

         12. 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.

         13. 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

        Exclusion Criteria

          1. Patients are excluded if they have liver tumor volume > 50%

          2. 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.

          3. 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

          4. 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.

          5. 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.

          6. Patients are excluded if they have a history of prior treatment with ipilimumab or
             CTLA-4 inhibitor.

          7. 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:safety and tolerability of sequential selective internal radiation with Yttrium90 followed by immunotherapy with ipilimumab and nivolumab.
Time Frame:3 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Preliminary clinical efficacy
Time Frame:2 years
Safety Issue:
Description:co-endpoints for this measure will be RECIST response rate and PFS
Measure:immunological changes
Time Frame:2 years
Safety Issue:
Description:Changes in peripheral blood lymphocyte counts
Measure:Correlation of tissue markers and response to immunotherapy
Time Frame:2 years
Safety Issue:
Description:Study of archival tumor tissue for tumor mutations, PDL-1, PDL-2, others
Measure:Explore relationship of response to immunotherapy with tumor melanin
Time Frame:2 years
Safety Issue:
Description:Correlate response with tumor production of melanin assessed by tumor density on MRI scans

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:David Minor, MD

Trial Keywords

  • uveal melanoma
  • liver metastases

Last Updated

December 8, 2016