A study to test safety and efficacy of treatment with ipilimumab and nivolumab in patients suffering from melanoma having 4 and more brain metastases

Phase 1

• Conditions: Patients with stage IV melanoma and four or more symptomatic brain metastases, who are not eligible for surgery or radiosurgery; MedDRA version: 21.1 Level: LLT Classification code 10025655 Term: Malignant melanoma of skin System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10006128 Term: Brain metastases System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10025650 Term: Malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10027480 Term: Metastatic malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004614-10-DE
• Lead Sponsor: niversity Hospital Tübingen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-16
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 68

Inclusion Criteria

1.Signed Informed Consent (ICF) prior to any screening procedures being performed
2.Ability to comply with protocol requirements
3.Metastatic histologically confirmed melanoma (per AJCC staging system) that is unresectable
4.Presence of four or more active brain metastasis confirmed/evaluated by MRI
Patients with symptomatic brain metastases will be defined as subjects with brain metastases and any of the following: focal neurological deficits, seizures, headache or any other neurological and/or psychiatric alteration with temporal relation to the diagnosis of CNS disease
5.Measurable disease by MRI per iRANO and RECIST 1.1 criteria
6.The time between the baseline MRI and the date of registration should not exceed 28 days. Steroid treatment is permissible before brain MRI evaluation but the dose should have been stable for at least 7 days and should be carefully documented
7.Patient must agree to the cerebro-spinal fluid (CSF) collections which are planned according to the study protocol.
8.Patients naïve for systemic treatment are eligible
9.Patients pre-treated with systemic immunotherapy, targeted therapy or chemotherapy are eligible, with the exception of previous treatment with the combination of CTLA-4 and PD-1 antibodies (see exclusion criterion 2)
10.Patients must have recovered completely from any treatment-related acute toxicity associated with prior therapy
11.At least two weeks must have passed since the last systemic anti-cancer treatment
12.Patients with prior local therapy of brain metastases are eligible
13.Patients may have received irradiation therapies:
a.A) None
b.B) Whole brain irradiation only
c.C) Stereotactic irradiation of single or few metastases. Such lesions cannot be selected as target lesions and must therefore be excluded for the evaluation of the IC-DCR
d.D) Combined B+C)
14.Screening laboratory values must meet the following criteria (using CTCAE v4.0)
and should be obtained within 14 days prior to registration:
•WBC = 2,000/µL
•Neutrophils = 1,500/µL
•Platelets = 100 x103/µL
•Hemoglobin > 9.0 g/dL
•Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (if using the Cockcroft-Gault formula below):
oFemale CrCl = (140 - age in years) x weight in kg x 0.85 / (72 x serum creatinine in mg/dL)
oMale CrCl = (140 - age in years) x weight in kg x 1.00 / (72 x serum creatinine in mg/dL)
•AST/ALT= 3 x ULN
•Total bilirubin = 1.5 x ULN (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
•INR = 1.5
15.ECOG Performance Status 0, 1 or 2
16.Expected life expectancy of =three months
17.Males and females = 18 years old
18.Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug
19.Women must not be breastfeeding
20.Women of childbearing potentia

Exclusion Criteria

1.Diagnosed ocular melanoma
2.Previous systemic therapy with the combination of CTLA-4 and PD-1 antibodies
3.Use of any investigational or non-registered product within the 30 days before registration in the study
4.Prior active malignancy within the previous 3 years except 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.History of organ transplantation
6.Active infection requiring systemic therapy
7.Active, known or suspected autoimmune disease.
Exceptions: Patients with controlled Type I diabetes mellitus (patients who keep their preprandial blood glucose within the target range of 4 to 7 mmol/L), hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, can be enrolled.
8.Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
9.Any serious or uncontrolled medical disorders thatmay increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results in the opinion of the investigator.
10.Known substance abuse or psychiatric disorders that would preclude cooperation with tany requirements of the trial.
11.Legal incapacity or limited legal capacity
12.Administration of live, attenuated vaccine within 4 weeks prior to the start of study drug
13.Positive test for hepatitis B virus surface antigen (HBs Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
14.Known history of a positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
15.Patients with known allergy or hypersensitivity to any of the study drugs or excipients
Patients with results of imaging or radiological examinations indicating increased cerebral pressure which would prevent lumbar puncture

Study & Design

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