Phase II multicente, non randomized, open label trial of nivolumab in combination with ipilimumab in subjects with previously untreated metastatic uveal melanoma.

• Conditions: Metastatic uveal melanoma non suitable for radical resection.; MedDRA version: 18.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004429-15-ES
• Lead Sponsor: GRUPO ESPAÑOL MULTICISPLINAR DE MELANOMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-12-30
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Written informed consent must be provided;
2. Patients must have a histological diagnosis of uveal melanoma;
3. Progressive metastatic disease at baseline. Progressive disease is defined asnew or progressive lesions on cross-sectional imaging;
4. Age>18 years;
5. ECOG performance status (PS) 0 to 1;
6. Measurable disease by CT or MRI per RECIST 1.1 criteria;
7. No active or chronic infection with HIV, Hepatitis B or Hepatitis C;
8. Adequate organ function as determine by the following criteria:
a. Absolute neutrophil count (ANC) ?1.500/uL.
b.WBC ?2.000/uL.
c.Platelet count ?100x 103
d. Haemoglobin ?9 g/dl.
e. Serum creatinine <2.5 x upper limit of normal (ULN) and creatinine clearance >40 mL/min
f. Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) <3 x ULN, or <5 x ULN if liver abnormalities are due to underlying malignancy.
g. Total bilirubin <= 1.5 x ULN, (except patients with Gilbert?s Syndrome, who must have a total bilirubin less than 3.0 mg/dL).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

1) Prior systemic treatment for metastatic uveal melanoma.
2) 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.
3) Autoimmune disease: Patients with a history of inflammatory bowel disease,
including ulcerative colitis and Crohn?s Diseasse, 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 syatemic
treatment, or conditions not expected to recur in the absence of an external trigger are
permited to enroll.
4) 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 AEs, such as a condition associated with frequent
diarrhea.
5) 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).
6) 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.
7) 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, 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.
8) 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 quivalents) for at least 2 weeks prior to study drug administration.
9) Women of childbearing potential (WOCBP) as defined below, who:
a. 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
b. have a positive pregnancy test at baseline, or
c. are pregnant or breastfeeding.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified