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

NCT02913417 | Unknown Phase 1 DMC

• 1 other identifier: Uveal Melanoma IIP
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

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.

Conditions

Uveal Melanoma; Hepatic Metastases

Keywords

uveal melanoma; liver metastases

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Secondary Outcomes (4)

• Preliminary clinical efficacy

  5 years

• immunological changes

  5 years

• Correlation of tissue markers and response to immunotherapy

  5 years

• Explore relationship of response to immunotherapy with tumor melanin

  5years

Study Arms (1)

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

Device: SIR-Spheres® Yttrium 90; Drug: ipilimumab; Drug: nivolumab

Interventions

SIR-Spheres® Yttrium 90 DEVICE

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

hepatic radiation followed by immunotherapy

ipilimumab DRUG

ipilimumab 1mg/kg every 3 weeks x 4

Also known as: Yervoy

hepatic radiation followed by immunotherapy

nivolumab DRUG

nivolumab 3mg/kg every 3 weeks x 4 then 480mg q 4 weeks

Also known as: Opdivo

hepatic radiation followed by immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• David Minor, MD: lead
• California Pacific Medical Center: collaborator
• Jefferson Medical College of Thomas Jefferson University: collaborator
• University of Chicago: collaborator

Study Sites (3)

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Jefferson Medical College of Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• 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.

  PMID: 35021863 DERIVED

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David R. Minor, M.D.

  California Pacific Medical Center Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Director Melanoma Center

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: September 23, 2016
• Study Start: October 10, 2016
• Primary Completion: January 1, 2022
• Study Completion: June 1, 2023
• Last Updated: April 19, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)