Melanoma Metastasized to the Brain and Steroids

NCT03563729 | Recruiting Phase 2

• 1 other identifier: MM1807
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

This clinical trial is to clarify whether treatment with a checkpoint inhibitor alone (pembrolizumab) or two in combination (ipilimumab and nivolumab), results in clinical benefit for MM patients with brain metastases and in need of steroid treatment. Patients will be treated in four arms depending on steroid dose level at inclusion (\> 10 \< 25 mg prednisolone or \> 25 mg prednisolone) and treatment (pembrolizumab alone or the combination of ipilimumab and nivolumab).

Conditions

Malignant Melanoma

Keywords

Immune therapy; checkpoint inhibitor; pembrolizumab; ipilimumab; nivolumab; steroid; brain metastasis; BRAF inhibitor; MEK inhibitor

Outcome Measures

Primary Outcomes (2)

• 6 months progression-free survival rate

  Proportion of patients who did not progress or die within 6 months from commencing study treatment.

  6 months

• 6 months overall survival rate

  Proportion of patients who did not die within 6 months from commencing study treatment.

  6 months

Secondary Outcomes (7)

• Overall progression-free survival

  4 years

• Overall survival

  4 years

• Overall response rate

  4 years

• Extracranial response rate

  4 years

• Intracranial response rate

  4 years

Study Arms (4)

B: Pembrolizumab (Prednisolone >10 mg)

EXPERIMENTAL

Intravenous infusion of pembrolizumab 2 mg/kg every third week for up to two years.

Drug: Pembrolizumab Injection [Keytruda]

C: Ipilimumab/nivolumab (Prednisolone 11-25 mg)

EXPERIMENTAL

Intravenous infusion of ipilimumab 3 mg/kg and nivolumab 1 mg/kg four times every three weeks in the induction phase and nivolumab 480 mg every four weeks in the maintenance phase for up to two years.

Drug: Ipilimumab Injection [Yervoy]; Drug: Nivolumab Injection [Opdivo]

D: Ipilimumab/nivolumab (Prednisolone >25 mg)

EXPERIMENTAL

Intravenous infusion of ipilimumab 3 mg/kg and nivolumab 1 mg/kg four times every three weeks in the induction phase and nivolumab 480 mg every four weeks in the maintenance phase for up to two years.

Drug: Ipilimumab Injection [Yervoy]; Drug: Nivolumab Injection [Opdivo]

E: BRAF/MEK -> ipi/nivo (prednisolone >10 mg)

EXPERIMENTAL

Induction treatment with BRAF/MEK inhibitors (either the combination of encorafenib/binimetinib or dabrafenib/trametinib) orally for 28 days followed by intravenous infusion of ipilimumab 3 mg/kg and nivolumab 1 mg/kg four times every three weeks in the induction phase and nivolumab 480 mg every four weeks in the maintenance phase for up to two years.

Drug: Ipilimumab Injection [Yervoy]; Drug: Nivolumab Injection [Opdivo]; Drug: Encorafenib; Drug: Binimetinib; Drug: Dabrafenib; Drug: Trametinib

Interventions

Pembrolizumab Injection [Keytruda] DRUG

Alone

B: Pembrolizumab (Prednisolone >10 mg)

Ipilimumab Injection [Yervoy] DRUG

In combination with nivolumab.

C: Ipilimumab/nivolumab (Prednisolone 11-25 mg); D: Ipilimumab/nivolumab (Prednisolone >25 mg); E: BRAF/MEK -> ipi/nivo (prednisolone >10 mg)

Nivolumab Injection [Opdivo] DRUG

In combination with ipilimumab.

C: Ipilimumab/nivolumab (Prednisolone 11-25 mg); D: Ipilimumab/nivolumab (Prednisolone >25 mg); E: BRAF/MEK -> ipi/nivo (prednisolone >10 mg)

Encorafenib DRUG

In combination with binimetinib

E: BRAF/MEK -> ipi/nivo (prednisolone >10 mg)

Binimetinib DRUG

In combination with encorafenib

E: BRAF/MEK -> ipi/nivo (prednisolone >10 mg)

Dabrafenib DRUG

In combination with dabrafenib

E: BRAF/MEK -> ipi/nivo (prednisolone >10 mg)

Trametinib DRUG

In combination with trametinib

E: BRAF/MEK -> ipi/nivo (prednisolone >10 mg)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed metastatic melanoma with radiologically verified brain metastasis
• Need for systemic steroid treatment (prednisolone \> 10 mg daily; dexamethasone \> 1.6 mg daily, hydrocortisone \> 40 mg daily or equivalent) due to brain metastasis
• At least one measurable lesion according to RECIST version 1.1 guidelines
• Evaluable intracranial disease
• years of age or older
• Performance status 0-2
• Able to undergo MRI with gadolinium contrast agent
• Adequate hematological and organ function
• No significant toxicity from previous cancer treatments (CTC\<1)
• Women of childbearing potential: Negative serum pregnancy test and must use effective contraception. This applies from screening and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered effective contraceptives
• Men with female partner of childbearing potential must use effective contraception from screening and until 6 months after treatment. Effective contraceptives are as described above for the female partner. In addition documented vasectomy and sterility or double barrier contraception are considered effective contraceptives
• Signed statement of consent after receiving oral and written study information.
• Willingness to participate in the planned treatment and follow-up and capable of handling toxicities.
• For arm E specifically: Tumor cells must harbor BRAF mutation.

You may not qualify if:

• Another malignancy or concurrent malignancy unless disease-free for 3 years
• Ocular melanoma
• Neurological symptoms from brain metastases present at baseline despite steroid treatment, unless symptoms are related to prior surgery
• Known hypersensitivity to one of the active drugs or excipients
• Acute or chronic infections with HIV or hepatitis
• Any medical condition that will interfere with patient compliance or safety
• Prior treatment with anti-PD-1/PD-L1/PD-L2/CTLA-4 antibodies in the metastatic setting
• Prior systemic treatment with anti-PD-1/PD-L1/PD-L2/CTLA-4 antibodies in the adjuvant setting, unless completed more than 6 months before enrolment in this study
• Simultaneous treatment with other experimental drugs or other anti-cancer drugs
• Pregnant or breastfeeding females.
• For arm E specifically: Prior treatment with BRAF/MEK inhibitors.

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (3)

Herlev Universityhospital

Herlev, Capital Region, 2730, Denmark

RECRUITING

Aarhus Universityhospital

Aarhus, Midt, 8000, Denmark

NOT YET RECRUITING

Odense Universityhospital

Odense, Syd, 5000, Denmark

NOT YET RECRUITING

Related Links

• Homepage of Center for Cancer Immune Therapy

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

pembrolizumab; Ipilimumab; Nivolumab; encorafenib; binimetinib; dabrafenib; trametinib

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

• Troels H Borch, PhD

  Center for Cancer Immune Therapy, Department of Hematology and Department of Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Inge M Svane, Professor

CONTACT

004538683868; inge.marie.svane@regionh.dk

Troels H Borch, PhD

CONTACT

004538683868; troels.holz.borch@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, PhD

Model Details: Six patients are enrolled in each arm. If clinical benefit is observed, each arm will be expanded to enroll a total of 20 patients.

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: June 20, 2018
• Study Start: June 6, 2018
• Primary Completion: June 1, 2024
• Study Completion (Estimated): June 6, 2028
• Last Updated: July 13, 2023

Record last verified: 2023-07

Locations

DK (3)