An open-label, single-arm, phase II, multicenter study to evaluate the efficacy of nivolumab in metastatic melanoma patients with symptomatic brain metastases.

Phase 2

Completed

Conditions: advanced melanoma
Metastatic melanoma
10027476

Registration Number: NL-OMON42782

Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 70

Inclusion Criteria

1.Subjects must sign informed consent prior to inclusion in this trial.
2.Subjects must be *18 years of age and competent to give informed consent.
3.Subjects must have a histologically confirmed diagnosis of stage IV melanoma.
4.Subjects must have clinical symptoms that are relatable to the intracranial lesions as assessed by a neurologist.
5.At least one new cerebral lesion on MRI, measurable by RANO-BM criteria (longest diameter * 10 mm and perpendicular diameter * 5 mm), must be present. Lesions with prior local treatment (i.e., SRT or surgical resection) are considered measurable if progression since the time of local treatment has been demonstrated. Leptomeningeal metastases are allowed, but will not be labeled target lesions.
6.Treatment with BRAF-inhibitors during a maximum of eight weeks is allowed for patients with a positive BRAF-mutational status.
7.Subjects must be treatment-naive to nivolumab.
8.Subjects must score 0 * 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
9.Subjects must have adequate organ function as defined by the following laboratory values (determined within 28 days prior to randomization and registration):
*White blood cells (WBC) * 2000 /µL
*Absolute neutrophil count (ANC) * 1500 /µL
*Platelets * 100 x103 /µL
*Hemoglobin * 9 g/dL or * 5.6 mmol/L
*Serum creatinine * 1.5 times upper limit of normal (ULN) or creatinine clearance > 40 ml/min (using the Cockcroft-Gault formula)
*Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) * 3 times ULN
*Bilirubin * 1.5 times ULN (Except patient with Gilbert Syndrome, who can have total bilirubin * 3.0 mg/dL)
*LDH < 2 times ULN
10.Women of childbearing potential (WOCBP) should have a negative urine or serum pregnancy test within 24 hours prior to receiving the first administration of nivolumab. Women with non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for * 1 year.
11.WOCBP and men who are sexually active with WOCBP must agree to use appropriate method(s) of contraception.

Exclusion Criteria

1.Subjects who have been treated with an anti-PD-1, anti-PD-L1, anti-PD-L2 antibody previously.
2.Subjects who have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 1 or better from adverse events due to previous cancer therapy.
3.Evidence for an active autoimmune disease, known or suspected. Potential subjects diagnosed 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.
4.Subjects treated with corticosteroids in an increasing dosage 7 days prior to the first administration of nivolumab. (A stable or decreasing dosage of * 4 mg dexamethasone or equivalent is allowed. In addition, inhaled or topical steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease.)
5.Known history of other (non-melanoma) malignancies, with the exception of non-melanoma skin cancers, in situ bladder cancer, gastric or colon cancers andcervical cancers/dysplasia or breast carcinoma in situ or patients in whom a complete remission was achieved at least 1 year prior to study entry and no additional therapy is required nor anticipated during the study period.
6.Known history of severe hypersensitivity reaction to treatment with monoclonal antibodies, or known hypersensitivity to study drug components.
7.Acute or chronic hepatitis B or C infection, indicated by a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody).
8.Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
9.Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or impairs the ability of the patient to receive protocol therapy.
10.A known psychiatric or substance abuse disorder that could interfere with cancer therapy.
11.Women of childbearing potential with a positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab.
12.Breastfeeding women.
13.Inability to comply with other requirements of the protocol.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Main endpoint of this study is the best overall response rate (BORR) of all<br /><br>previously determined target lesions in the brain, which will be determined<br /><br>according to the Response Assessment in Neuro-Oncology Brain Metastases<br /><br>(RANO-BM) criteria.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary efficacy endpoints that will be determined are: duration of response<br /><br>(DOR), time to development of new brain metastases in responding patients,<br /><br>progression-free survival, and overall survival. </p><br>