A clinical trial with investigational compounds INC280 and BKM120 in adult patients with recurrent glioblastoma

Phase 1

• Conditions: Glioblastoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-000699-14-NL
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-17
• Last Update Posted: 6 February 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• = 18 years of age.
• Histologically confirmed diagnosis of glioblastoma after initial tumor resection with radiographic evidence of recurrent tumor per RANO criteria.
• Phase Ib: Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score < 10) by IHC confirmed by local documentation (phase Ib only) or central assessment
• Phase II: Documented evidence of PTEN mutations, homozynous deletion of PTEN or PTEN negative (H score < 10) by IHC or c-Met amplification (GCN > 5) by FISH, all assessed centrally. Fusion transcripts or mutant c-Met (based on local data) may be eligible for single agent arm after documented agreement with Novartis.
• Must have received the following treatment for glioblastoma:
- Prior adjuvant treatment with radiotherapy and temozolomide;
- Note: A maximum of two prior chemotherapy/antibody regimens (including bevacizumab or other direct VEFG/VEGFR inhibitors) for recurrent disease are permitted.
• Representative archival glioblastoma sample (formalin-fixed paraffine embedded tissue) must be available.
• ECOG performance status = 2.
• Able to swallow and retain oral medication.
• Patients in the surgical arm only: patients with recurrent glioblastoma must be eligible for surgical resection as deemed by the site Investigator.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

• Prior or current treatment with a c-MET inhibitor or HGF-targeting therapy
• Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma or for pre-existing neoplasm transformed to glioblastoma (applicable for combination treatment arm only).
• Receiving treatment with medications that are known strong inhibitors or inducers of CYP3A, and cannot be discontinued 7 days prior to the start of the treatment and during the course of the study.
• Receiving treatment with medications that are known CYP3A or CYP1A2 substrates with narrow therapeutic index, and cannot be discontinued during the course of the study.
• Currently being treated with Enzyme Inducing Anti-Epileptic Drug (EIAED). If previously on an EIAED, the patient must be off of it for at least 2 weeks prior to study treatment.
• Currently receiving warfarin or other coumadin-derived anticoagulants for treatment, prophylaxis or otherwise.
• Currently receiving increasing or chronic treatment ( > 5 days) with corticosteroids or another immunosuppressive agent.
• History of acute or chronic pancreatitis or any risk factors that may increase the risk of pancreatitis.
• Active cardiac disease or a history of cardiac dysfunction.
• Impairment of gastrointestinal (GI) function or GI disease that might significantly alter the absorption of study drug
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM- IV).
• Anxiety = CTCAE grade 3
• Any of the following baseline laboratory values:
- Hemoglobin < 9 g/dL
- Platelet count < 75 x 109/L
- Absolute neutrophil count (ANC) < 1.0 x 109/L
-INR > 1.5
- Serum lipase > normal limits for the institution
- Asymptomatic serum amylase > grade 2
- Potassium, magnesium, and calcium (corrected for albumin) > normal limits for the institution
- Total bilirubin >1.5 x upper limit of normal (ULN)
- Serum creatinine >1.5 x ULN or creatinine clearance = 45 mL/min
- Alanine aminotransferase (AST) or aspartate aminotransferase (ALT) > 3.0 x ULN (or > 5.0 X ULN if liver metastases are present)
- Fasting plasma glucose > 120mg/dL or > 6.7 mmol/L
- HbA1c > 8%.

Study & Design

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