Evaluation of Safety and Efficacy of Patients With Four and More Symptomatic Brain Metastases of Melanoma

NCT03728465 | Terminated Phase 2

• 1 other identifier: CA209-429
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 11

Brief Summary

Up to 50% of patients with unresectable metastatic melanoma will develop brain metastases during their lifetime. A possible treatment options for patients with brain metastases are surgery and radiotherapy but usually for lesions in the range of \< 3 brain metastases. This study was performed to evaluate the addition of immune checkpoint inhibitors in patients with stage IV melanoma with \> 3 symptomatic brain metastases, who are not eligible for surgery or radiosurgery.

Conditions

Metastatic Melanoma; Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Intracranial Control Rate after 6 months of treatment

  Proportion of patients with complete intracranial responses (CR), partial intracranial responses (PR) or stable intracranial disease (SD) after 6 months of treatment.

  6 months

Secondary Outcomes (8)

• Overall survival

  2 years

• Progression-free survival

  2 years

• Stereotactic irradiation or surgery of brain metastases after partial tumor remission

  2 years

• Tolerability according to NCI-CTCAE-Criteria

  2 years

• Best Overall Response Rate with Complete Respone (CR)

  6 months

Study Arms (1)

Treatment Phase

EXPERIMENTAL

Treatment phase is divided into the "Induction Phase" and "Maintenance Phase". During the induction phase patients are treated with 1 mg/kg nivolumab and 3 mg/kg ipilimumab, during the maintenance phase with nivolumab 3 mg/kg only .

Biological: Nivolumab; Biological: Ipilimumab

Interventions

Nivolumab BIOLOGICAL

In the induction phase of this study nivolumab is administered as a IV infusion in combination with ipilimumab at a dose of 1 mg/kg for 4 cycles at three weeks interval and in a maintenance phase alone at a dose of 3 mg/kg every two weeks.

Also known as: OPDIVO

Treatment Phase

Ipilimumab BIOLOGICAL

In the induction phase of this study ipilimumab is administered as a IV infusion in combination with nivolumab at a dose of 3 mg/kg for 4 cycles at three weeks interval.

Also known as: YERVOY

Treatment Phase

Eligibility Criteria

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

You may qualify if:

• Signed informed consent (ICF) prior to any screening procedures being performed
• Ability to comply with protocol requirements
• Metastatic histologically confirmed melanoma that is unresectable
• Presence of \> 3 active brain metastases confirmed/evaluated by MRI
• Measurable disease by MRI per iRANO and RECIST 1.1 criteria
• 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
• Patient must agree to the cerebro-spinal fluid (CSF) collections according to the study protocol
• Patients naïve for systemic treatment are eligible
• Patients pretreated with systemic immunotherapy, targeted therapy or chemotherapy are eligible (exception: previous treatment with the combination of CTLA-4 and PD-1 antibodies)
• Patients must have recovered completely from any treatment-related acute toxicity associated with prior therapy
• At least two weeks must have passed since the last systemic anti-cancer treatment
• Patients with prior local therapy of brain metastases are eligible
• Patients may have received irradiation therapies: A) None; B) Whole brain irradiation only, C) Stereotactic irradiation of single or few metastases, D) Combined B+C)
• Screening laboratory values within 14 days prior to registration must meet the criteria: 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, 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
• ECOG Performance Status 0, 1 or 2

You may not qualify if:

• Diagnosed ocular melanoma
• Previous systemic therapy with the combination of CTLA-4 and PD-1 antibodies
• Use of any investigational or non-registered product within the 30 days before registration in the study
• 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
• History of organ transplantation
• Active infection requiring systemic therapy
• Active, known or suspected autoimmune disease (exceptions: patients with controlled Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment).
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• 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
• Known substance abuse or psychiatric disorders that would preclude cooperation with tany requirements of the trial
• Legal incapacity or limited legal capacity
• Administration of live, attenuated vaccine within 4 weeks prior to the start of study drug
• Positive test for HBs Ag or HCV antibody
• Known history of a positive test for HIV or known AIDS
• Patients with known allergy or hypersensitivity to any of the study drugs or excipients

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (11)

Elbe Kliniken Stade - Buxtehude GmbH

Buxtehude, Germany

Location

Universitätsklinik Carl Gustav Carus Dresden

Dresden, Germany

Location

HELIOS Klinikum Erfurt

Erfurt, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

Gesellschaft für Klinische Forschung Ludwigshafen mbH

Ludwigshafen, Germany

Location

Universitätsklinikum Mannheim

Mannheim, Germany

Location

Klinikum rechts der Isar

München, Germany

Location

Harzklinikum Dorothea Christiane Erxleben GmbH

Quedlinburg, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System 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

• Claus Garbe, Prof.Dr.med.

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

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: October 19, 2018
• First Posted: November 2, 2018
• Study Start: April 10, 2018
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: February 3, 2021

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11)