Phase Ib/II Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme

NCT ID: NCT01934361

Last Updated: 2020-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2016-07-07

Brief Summary

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This is a multi-center, phase Ib/ II study (two parts) with patients that had recurrent glioblastoma multiforme. The first part (phase Ib) was to investigate the maximum tolerated dose/Recommended phase ll dose (MTD/RP2D) of once daily buparlisib in combination with every-three-week carboplatin or buparlisib once daily in combination with every-six-week lomustine (CCNU) using a Bayesian model. Once MTD/ RP2D is established in either of the 2 arms, the corresponding phase II portion of the study was to start. Phase II was to assess the treatment effect of buparlisib in combination with carboplatin in terms of Progression Free Survival (PFS) and was to compare the treatment effect of buparlisib with lomustine versus lomustine plus placebo in terms of PFS.

A preliminary assessment for both combinations (buparlisib plus carboplatin or lomustine) demonstrated that there was not enough antitumor activity compared to historical data with single agent carboplatin or lomustine. Based on the overall safety profile, and preliminary anti-tumor activity observed in this study, Novartis decided that no additional patients would be enrolled into this study. As a consequence, the Phase II part of the study was not conducted.

Detailed Description

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Conditions

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Recurrent Glioblastoma Multiforme

Keywords

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BKM120 Recurrent glioblastoma multiforme rGBM buparlisib

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Lomustine+ buparlisib (Phase Ib)

Group Type EXPERIMENTAL

buparlisib

Intervention Type DRUG

Buparlisib administered orally on a continuous daily schedule. Buparlisib is manufactured as 10mg and 50mg hard gelatin capsules.

lomustine

Intervention Type DRUG

Lomustine will be administered as a single oral dose of 100 mg/m² every 6 weeks in a 42 day cycles.

carboplatin+ buparlisib (Phase Ib)

Group Type EXPERIMENTAL

buparlisib

Intervention Type DRUG

Buparlisib administered orally on a continuous daily schedule. Buparlisib is manufactured as 10mg and 50mg hard gelatin capsules.

carboplatin

Intervention Type DRUG

Carboplatin intravenous infusion will be administered at a dose of AUC 5 in a 21 day cycle (every 3 weeks).

lomustine+ buparlisib (Phase II)

Group Type EXPERIMENTAL

buparlisib

Intervention Type DRUG

Buparlisib administered orally on a continuous daily schedule. Buparlisib is manufactured as 10mg and 50mg hard gelatin capsules.

lomustine

Intervention Type DRUG

Lomustine will be administered as a single oral dose of 100 mg/m² every 6 weeks in a 42 day cycles.

lumustine + placebo (Phase II)

Group Type PLACEBO_COMPARATOR

lomustine

Intervention Type DRUG

Lomustine will be administered as a single oral dose of 100 mg/m² every 6 weeks in a 42 day cycles.

placebo

Intervention Type DRUG

Placebo will be administered orally on a continuous QD dosing schedule for cycles of 42 days. Buparlisib matching placebo is manufactured as 10 mg and 50 mg hard gelatin capsules.

carboplatin+ buparlisib (Phase II)

Group Type EXPERIMENTAL

buparlisib

Intervention Type DRUG

Buparlisib administered orally on a continuous daily schedule. Buparlisib is manufactured as 10mg and 50mg hard gelatin capsules.

carboplatin

Intervention Type DRUG

Carboplatin intravenous infusion will be administered at a dose of AUC 5 in a 21 day cycle (every 3 weeks).

Interventions

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buparlisib

Buparlisib administered orally on a continuous daily schedule. Buparlisib is manufactured as 10mg and 50mg hard gelatin capsules.

Intervention Type DRUG

carboplatin

Carboplatin intravenous infusion will be administered at a dose of AUC 5 in a 21 day cycle (every 3 weeks).

Intervention Type DRUG

lomustine

Lomustine will be administered as a single oral dose of 100 mg/m² every 6 weeks in a 42 day cycles.

Intervention Type DRUG

placebo

Placebo will be administered orally on a continuous QD dosing schedule for cycles of 42 days. Buparlisib matching placebo is manufactured as 10 mg and 50 mg hard gelatin capsules.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient is an adult ≥ 18 years old at the time of informed consent.
* Patient has histologically confirmed diagnosis of GBM with documented recurrence after first line treatment including radiotherapy and TMZ (SoC), not suitable for curative surgery or re-irradiation.
* Patient has at least one measurable and/or non-measurable lesion as per RANO criteria
* Patient has recovered (to Grade ≤1) from all clinically significant toxicities related to prior antineoplastic therapies.
* Patient has Karnofsky performance status (KPS) ≥70%.
* Patient has adequate organ and bone marrow functions:

* Absolute Neutrophils Count (ANC) ≥ 1.5 x 109/L
* Platelets ≥ 100 x 109/L (in case of transfusion stable for ≥14 days prior to treatment start)
* Hemoglobin ≥ 9.0 g/dL (in case of transfusion stable for ≥14 days prior to treatment start)
* INR ≤ 1,5
* Serum Creatinine ≤ 1.5 x ULN, or Creatinine Clearance \> 45mL/min
* Potassium and calcium (corrected for albumin), sodium and magnesium within institutional normal limits
* Serum Bilirubin ≤ ULN, AST and ALT ≤ ULN
* HbA1c ≤ 8%
* Fasting plasma glucose (FPG) ≤ 120 mg/dL or ≤ 6.7 mmol/L
* Patient has tumor tissues available (archival or fresh).

Exclusion Criteria

* Patient has received previous treatment with PI3K inhibitors, lomustine or carboplatin.
* Patient has received previous antineoplastic treatment for recurrent GBM (e.g. VEGF inhibitors, cytotoxic agents).
* Patient has received more than one line of cytotoxic chemotherapy
* Patient has concurrent use of anti-neoplastic agents including investigational therapy
* Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
* Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. 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 randomization is allowed.
* Patient is currently receiving an enzyme-inducing anti-epileptic drug (EIAED). The patient must have discontinued EIAED therapy for at least two weeks prior to starting study drug.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Barrow Neurological Insitute St. Joseph's Hospital

Phoenix, Arizona, United States

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

MD Anderson Cancer Center/University of Texas

Houston, Texas, United States

Site Status

Novartis Investigative Site

Heidelberg, Victoria, Australia

Site Status

Novartis Investigative Site

Parkville, Victoria, Australia

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Marseille, , France

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Saint-Herblain, , France

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Site Status

Countries

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Germany Hong Kong Italy South Korea Switzerland Thailand United States Australia Belgium Canada France Spain

References

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Rosenthal M, Clement PM, Campone M, Gil-Gil MJ, DeGroot J, Chinot O, Idbaih A, Gan H, Raizer J, Wen PY, Pineda E, Donnet V, Mills D, El-Hashimy M, Mason W. Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. ESMO Open. 2020 Jul;5(4):e000672. doi: 10.1136/esmoopen-2020-000672.

Reference Type DERIVED
PMID: 32665311 (View on PubMed)

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=16410

Results for CBMK120E2102 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

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2013-003129-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBKM120E2102

Identifier Type: -

Identifier Source: org_study_id