Buparlisib in Melanoma Patients Suffering From Brain Metastases (BUMPER)

NCT02452294 | Unknown Phase 2

• 1 other identifier: CBKM120ZDE01T
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

The study will enrol adult female and male patients with BRAF wild-type melanoma and brain metastases who are not eligible for surgery or radiosurgery and failed prior therapy with ipilimumab, and patients with BRAF V600 mutation-positive melanoma and brain metastases who are not eligible for surgery or radiosurgery and who failed prior therapy with a BRAF inhibitor.

Conditions

Malignant Melanoma; Metastases

Keywords

Brain

Outcome Measures

Primary Outcomes (1)

• Intracranial disease control rate

  Intracranial disease control rate - defined as the percentage of patients whose intracranial response is a confirmed complete response, partial response or stable disease assessed by investigators using modified RECIST 1.1 criteria

  6 weeks

Secondary Outcomes (6)

• Overall response rate

  12 weeks

• Duration of response for the subsets of patients with confirmed intracranial CR or PR

  Up to 60 weeks

• Duration of response for the subsets of patients with confirmed overall CR or PR

  Up to 60 weeks

• Progression free survival

  week 24

• Overall survival

  week 52

Study Arms (1)

Buparlisib

EXPERIMENTAL

Patients will receive oral buparlisib 100 mg once daily and continue on study treatment until evidence of disease progression, death, or unacceptable adverse events.

Drug: Buparlisib

Interventions

Buparlisib DRUG

Patients will receive oral buparlisib 100 mg once daily and continue on study treatment until evidence of disease progression, death, or unacceptable adverse events

Buparlisib

Eligibility Criteria

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

You may qualify if:

• Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements.
• Patient has adequate bone marrow and organ function as defined by the following laboratory values; (Clinical labs - performed within 14 days prior to enrolment)
• Hematology
• Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
• Platelet count ≥ 100 x 109/L (For patients with haematologic malignancies involving the bone marrow, platelet count \> 75 x 109/L)
• Haemoglobin ≥ 9.0 g/dL Coagulation
• INR ≤ 1.5
• Biochemistry e. Potassium and calcium (corrected for albumin), within normal limits for the institution, or ≤ Grade 1 if judged not clinically significant by the investigator f. Serum creatinine ≤ 1.5 x ULN and/or creatinine clearance \> 50% LLN (Lower Limit of Normal) g. Total Serum bilirubin ≤ ULN (or \<1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome, which is defined as presence of several episodes of unconjugated hyperbilirubinemia with normal results from CBC count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis h. AST (SGOT) and ALT (SGPT) below or equal upper limit of normal range or (≤ 3.0 x ULN if liver metastases are present) i. Fasting plasma glucose (FPG) ≤ 120mg/dL or ≤ 6.7 mmol/L j. HbA1c ≤ 8%
• Patient is able to swallow and retain oral medication
• Patient must be at least 18 years old
• Patient must have an estimated life expectancy \> 8 weeks in the opinion of the investigator
• Patient must have ECOG performance status \< 2
• Nature of illness and treatment history
• Histologically confirmed diagnosis of melanoma
• Patient must has shown evidence for PD in the brain by MRI without leptomeningeal disease

You may not qualify if:

• Patient has a known hypersensitivity to any of the excipients of buparlisib
• Patient who has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered to Grade 1 or better from related side effects of such therapy (except alopecia)
• Patient has not recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
• Patient is currently receiving increasing or chronic treatment (\> 5 days) with corticosteroids or another immunosuppressive agent;
• The following uses of corticosteroids are permitted: single doses; e.g. with standard premedication for taxanes; topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
• Patient taking an enzyme-inducing anti-epileptic drug (EIAED): phenobarbital, phenytoin, fosphenytoin, primidone, rufinamide carbamazepine, oxcarbazepine, eslicarbazepine, felbamate, and topiramate (only when daily dose exceeds 200 mg). Participant must be off any EIAEDs for at least two weeks prior to starting study
• Requirement of more than 4 mg dexamethasone daily
• Patient is being treated at start of study treatment with any of the following drugs:
• Drugs known to be strong inhibitors or inducers of isoenzyme CYP3A including herbal medications.
• Drugs with a known risk to induce Torsades de Pointes
• Note: The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to starting study treatment is allowed.
• Patient who has received prior treatment with a PI3K inhibitor, AKT inhibitor or mTOR inhibitor
• Patient who have received anti-angiogenic or anti-VEGF targeted agents
• Patient is currently receiving warfarin or any other coumarin-derivative anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• University Hospital Dresden: collaborator

Study Sites (2)

Department of Dermatology, University Hopsital

Dresden, 01307, Germany

RECRUITING

Department of Dermatology, University Hospital

Tübingen, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

NVP-BKM120

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Claus Garbe, MD

CONTACT

++49 7071 29; claus.garbe@med.uni-tuebingen.de

Thomas K Eigentler, MD

CONTACT

++49 7071 29; thomas.eigentler@med.uni-tuebingen.de

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: May 5, 2015
• First Posted: May 22, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: July 1, 2018
• Last Updated: May 3, 2017

Record last verified: 2017-05

Locations

DE (2)