PHASE 2 CLINICAL STUDY OF NIVOLUMAB COMBINED WITHIPILIMUMAB IN SUBJECTS WITH UNRESECTABLE OR METASTATIC MELANOMA. (NIVOLUMAB-IPILIMUMAB AT 1MG/KG – NIVOIPI01)

Phase 1

• Conditions: Adult unresectable metastatic melanoma patients either non pretreated or pretreated with B-Raf inhibitors or their combinationwith MEK inhibitors; MedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000742-61-IT
• Lead Sponsor: AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-01-30
• Last Update Posted: 12 February 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1 .Subjects capable of giving informed consent must have signed and dated an IRB/IEC approved written informed consent form
in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related
procedures that are not part of normal subject care.
2. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other
requirements of the study.
3. Histologically confirmed unresectable Stage III or Stage IV melanoma, as per AJCC staging system.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Refer to Appendix 4)
5. Treatment naïve subjects (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma). Note that prior
adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to randomization, and all
related adverse events have either returned to baseline or stabilized.
6. Measurable disease by CT or MRI per RECIST 1.1 criteria [89]
7. Tumor tissue from an unresectable or metastatic site of disease must be provided for disease diagnsis.
8. Subjects must have known BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional
standards during the Screening Period.
9. Prior radiotherapy must have been completed at least 2 weeks prior to study drug
administration.
10. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to study entry:
i) WBC = 2000/µL
ii) Neutrophils = 1500/µL
iii) Platelets =100 x103/µL
iv) Hemoglobin = 9.0 g/dL
v) Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (using the
Cockcroft-Gault formula):
Female CrCl = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dL
vi) AST/ALT = 3 x ULN
vii) Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
viii) normal ACTH level, and thyroid function tests, negative pregnancy test within 24 hours prior to the start of investigational
product.
11. Men and women, >18 years of age
12. Women of childbearing potential (WOCBP as defined below) and Men who are sexually active with WOCBP must use any
contraceptive method with a failure rate of less than 1% per year as indicated in Appendix 5 for at least 6 and 7,5 months,
respectively, after the last dose of investigational drug (see also 2014_09_HMA_CTFG_Contraception.pdf).
13. Subject must consent to undergo a biopsy of their metastasis for confirmation of the diagnosis and/or BRAF V600 mutational
testing
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1.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.
2.Ocular melanoma
3.Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study
participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the
interpretation of study results.
4.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, or carcinoma in situ of the prostate, cervix, or breast.
5.Subjects with active, known or suspected autoimmune disease. 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.
6.Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or
other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal
replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
7.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically
targeting T-cell costimulation or immune checkpoint pathways, are permitted only under exceptional circumstances and always
after PI approval.
8.Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute
or chronic infection, as determined in subjects where the condition is unknown at time of study entry.
9.Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
(AIDS).
10.History of allergy to study drug components.
11.History of severe hypersensitivity reaction to any monoclonal antibody.
12.WOCBP who are pregnant or breastfeeding
13.Women with a positive pregnancy test at enrollment or prior to administration of study medication.
14.Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Women of Childbearing Potential
Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone
surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Menopause is defined clinically as 12
months of amenorrhea in a woman over age 45 in the absence of other biological or physiological causes.In additional, women
under the age of 62 must have a documented serum follicle stimulating hormone, (FSH) level > 40mIU/mL.
Prohibited and/or Restricted Treatments
The following medications are prohibited during the study:
• Immunosuppressive agents (except to treat a drug-related adverse event)
• Systemic corticost

Study & Design

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