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

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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.

Brief Summary

      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 Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

safety and tolerability of sequential selective internal radiation with Yttrium90 followed by immunotherapy with ipilimumab and nivolumab.

Secondary Outcome

 Preliminary clinical efficacy

Condition

Uveal Melanoma

Intervention

SIR-Spheres® Yttrium 90

Study Arms / Comparison Groups

 hepatic radiation followed by immunotherapy
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Device

Estimated Enrollment

26

Start Date

October 10, 2016

Completion Date

June 2023

Primary Completion Date

January 2022

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).

          8. Patients are excluded if they have had prior hepatic arterial embolization therapy
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

David R. Minor, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02913417

Organization ID

Uveal Melanoma IIP


Responsible Party

Sponsor-Investigator

Study Sponsor

David Minor, MD

Collaborators

 California Pacific Medical Center

Study Sponsor

David R. Minor, M.D., Study Chair, California Pacific Medical Center Research Institute


Verification Date

April 2021