Trial of Nivolumab in Combination With Ipilimumab in Subjects With Previously Untreated Metastatic Uveal Melanoma

NCT02626962 | Completed Phase 2 DMC

• 2 other identifiers: GEM-14022015-004429-15
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 10

Brief Summary

This is a Phase 2, single-arm study of nivolumab combined with ipilimumab in subjects with previously untreated, unresectable or metastatic uveal melanoma. Previous studies with immunotherapy have shown promising results and this synergistic combination was very effective in other tumors. This study will allow for further characterization of the safety and clinical activity of nivolumab combined with ipilimumab in subjects with uveal melanoma.

Conditions

Uveal Melanoma

Keywords

melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival at 12 months

  Percentage of patients alive at 1-year from first dose of treatment.

  12 months after treatment start

Secondary Outcomes (6)

• Overall survival at 24 months.

  24 months

• Progression Free Survival (PFS)

  3 months

• Global PFS according to RECIST 1.1 criteria.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

• Objective Response Rate (ORR)

  12 months

• Disease Control Rate

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

Nivolumab and Ipilimumab every 3 weeks for a total of four doses (Cycles 1 and 2) followed by Nivolumab every 2 weeks

Drug: ipilimumab; Drug: Nivolumab

Interventions

ipilimumab DRUG

Ipilimumab every 3 weeks for a total of four doses (Cycles 1 and 2)

Also known as: Yervoy

Nivolumab and Ipilimumab

Nivolumab DRUG

Nivolumab every 3 weeks for a total of four doses (Cycles 1 and 2) followed by Nivolumab every 2 weeks

Also known as: Opdivo

Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be provided;
• Patients must have a histological diagnosis of uveal melanoma;
• Progressive metastatic disease at baseline. Progressive disease is defined as new or progressive lesions on cross-sectional imaging;
• Age\>18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1;
• Measurable disease by CT or MRI per RECIST 1.1 criteria;

You may not qualify if:

• Prior systemic treatment for metastatic uveal melanoma.
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast, or incidental prostate cancer.
• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of nivolumab and ipilimumab hazardous or obscure the interpretation of Advers Events (AEs), such as a condition associated with frequent diarrhea.
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of nivolumab and ipilimumab).
• A history of prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• Concomitant therapy with any of the following: Interleukin (IL) -2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids, defined as \>10mg daily prednisone equivalents. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
• Women of childbearing potential (WOCBP) as defined below, who:
• are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
• have a positive pregnancy test at baseline, or
• are pregnant or breastfeeding.

Sponsors & Collaborators

• Grupo Español Multidisciplinar de Melanoma: lead
• Bristol-Myers Squibb: collaborator

Study Sites (10)

Hospital Son Espases

Palma de Mallorca, Balearic Islands, Spain

Location

ICO Hospitalet

L'Hospitalet de Llobregat, Spain

Location

H. Insular de Canarias

Las Palmas de Gran Canaria, Spain

Location

Hospital La Paz

Madrid, Spain

Location

H. U. Virgen de la Victoria

Málaga, Spain

Location

Clínica Universidad de Navarra

Pamplona, Spain

Location

H. U. Clínico de Santiago

Santiago, Spain

Location

H.U. Virgen Macarena

Seville, Spain

Location

Hospital General Universitario de Valencia

Valencia, Spain

Location

H. C. U. de Valladolid

Valladolid, Spain

Location

Related Publications (1)

• Piulats JM, Espinosa E, de la Cruz Merino L, Varela M, Alonso Carrion L, Martin-Algarra S, Lopez Castro R, Curiel T, Rodriguez-Abreu D, Redrado M, Goma M, Rullan AJ, Calvo Gonzalez A, Berrocal-Jaime A. Nivolumab Plus Ipilimumab for Treatment-Naive Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol. 2021 Feb 20;39(6):586-598. doi: 10.1200/JCO.20.00550. Epub 2021 Jan 8.

  PMID: 33417511 DERIVED

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

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; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue 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

• Josep Maria Piulats, MD

  ICO Hospitalet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 10, 2015
• Study Start: April 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: July 22, 2021
• Last Updated: March 22, 2022

Record last verified: 2022-03

Locations

ES (10)