A clinical trial with investigational compounds INC280 and BKM120 in adult patients with recurrent glioblastoma.
- Conditions
- GlioblastomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-000699-14-ES
- Lead Sponsor
- ovartis Farmacéutica, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 66
? ? 18 years of age.
? Histologically confirmed diagnosis of glioblastoma after initial tumor resection with radiographic evidence of recurrent tumor per RANO criteria.
? Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative by IHC confirmed by local or central assessment
? Must have received the following treatment for glioblastoma:
- Prior adjuvant treatment with radiotherapy and temozolomide;
- A maximum of two prior chemotherapy regimens (including bevacizumab or other direct VEFG/VEGFR inhibitors) for recurrent disease are permitted.
? Representative archival or newly obtained tumor sample from glioblastoma (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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26
? Prior or current treatment with a c-MET inhibitor or HGF-targeting therapy
? Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma
? Received radiation (including therapeutic radioisotopes such as strontium 89) therapy ? 4 weeks prior to the first dose of study treatment and have not recovered from side effects of such therapy (? Grade 1) prior to the first dose of study treatment, except for alopecia.
? 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 ?2 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) > normal range (or < 3.0 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
- Primary Outcome Measures
Name Time Method Main Objective: Phase Ib: To estimate the safe dose of the combination INC280 and buparlisib.<br>Phase II: To estimate anti-tumor efficacy of the combination INC280 and buparlisib.<br>Surgical arm: To estimate the concentrations of INC280 and buparlisib in tumor tissue.;Secondary Objective: To characterize the safety of INC280 in combination with buparlisib.<br>To characterize the tolerability of INC280 in combination with buparlisib.<br>To determine pharmacokinetic profile of INC280 in combination with buparlisib. <br>To further assess the anti-tumor activity of INC280 in combination with buparlisib.<br>Phase Ib: To investigate drug level of INC280 and buparlisib in CSF (if available).;Primary end point(s): a) Phase II: Progression free survival rate (PFSR) <br>b) Phase Ib: Incidence of dose limiting toxicities (DLTs)<br>c) Surgical arm: Concentrations of INC280 and buparlisib in tumor;Timepoint(s) of evaluation of this end point: a) 6 months<br>b) 28 days <br>c) 7 days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1) Type, frequency, and severity of adverse events and serious adverse events. <br>2) Tolerability: dose interruptions, reductions and dose intensity. <br>3) Plasma concentration of INC280 and buparlisib, and PK parameters, including but not limited to Cmax, Tmax, AUCtau, and T1/2.<br>4) Overall response rate (ORR)<br>5) Concentration of INC280 and buparlisib in cerebrospinal fluid (if available). <br>6) Overall survival (OS);Timepoint(s) of evaluation of this end point: 1) 3 months <br>2) 3 months <br>3) 3 months <br>4) 12 months <br>5) 7 days <br>6) 12 months