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

Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Recurrent Glioblastoma Multiforme (rGBM)

Intervention: buparlisib (Drug); carboplatin (Drug); lomustine (Drug); placebo (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

Overall contact:
Novartis Pharmaceuticals, Phone: 1-888-669-6682

Summary

This is a multi-center, phase Ib/ II study (two parts) with patients that have recurrent glioblastoma multiforme. The first part (phase Ib) will 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 will start. Phase II will assess the treatment effect of buparlisib in combination with carboplatin in terms of Progression Free Survival (PFS) and will compare the treatment effect of buparlisib with lomustine versus lomustine plus placebo in terms of PFS.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Number of Total Dose-limiting Toxicity (DLT) during Dose Escalation part to determine Maximum Tolerated Dose (MTD) [Phase Ib]

12 week Progression Free Survival (PFS) rate (Phase II- Carboplatin combination)

Progression Free Survival (PFS) [phase II lomustine combinations]

Secondary outcome:

Frequency and severity of Adverse Events (AEs) [Phase Ib, Phase II, all treatment arms]

Overall Response Rate (ORR) as per Response Assessment in Neuro-Oncology (RANO) [Phase Ib , both combinations]

Progression Free Survival (PFS) [Phase Ib- both combinations]

Overall response rate (ORR) [Phae II, carboplatin combination]

Progression Free Survival (PFS) [Phase II, carboplatin combination]

24 week Progression Free Survival (PFS) rate (Phase II carboplatin combination)

Overall Survival (OS) (Phase II Carboplatin combination)

Overall Response Rate (ORR) (Phase II Lomustine combinations)

12 week Progression Free Survival (PFS) rate (Phase II- lomustine combinations)

24 week Progression Free Survival (PFS) rate (Phase II- lomustine combinations)

Overall survival (OS) [Phase II lomustine combinations]

Eligibility

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

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. Other protocol-defined Inclusion/exclusion criteria may apply.

Locations and Contacts

Novartis Pharmaceuticals, Phone: 1-888-669-6682

Novartis Investigative Site, Leuven 3000, Belgium; Recruiting

Novartis Investigative Site, Bobigny 93009, France; Not yet recruiting

Novartis Investigative Site, Marseille Cedex 05 13885, France; Recruiting

Novartis Investigative Site, Paris Cedex 13 75651, France; Recruiting

Novartis Investigative Site, Saint Herblain cedex 44805, France; Recruiting

Novartis Investigative Site, Bonn 53105, Germany; Not yet recruiting

Novartis Investigative Site, Freiburg 79106, Germany; Not yet recruiting

Novartis Investigative Site, Regensburg 93053, Germany; Not yet recruiting

Novartis Investigative Site, Hong Kong, Hong Kong; Not yet recruiting

Novartis Investigative Site, Napoli 80131, Italy; Withdrawn

Novartis Investigative Site, Madrid 28007, Spain; Not yet recruiting

Novartis Investigative Site, Genève 1211, Switzerland; Not yet recruiting

Novartis Investigative Site, Zurich 8091, Switzerland; Not yet recruiting

Novartis Investigative Site, Bangkok 10330, Thailand; Not yet recruiting

Novartis Investigative Site, Bangkok 10700, Thailand; Not yet recruiting

Ironwood Cancer and Research Centers SC, Chandler, Arizona 85224, United States; Recruiting
Holly Joice, Email: HJoice@ironwoodcrc.com
Mikhail I. Shtivelband, Principal Investigator

Barrow Neurological Insitute St. Joseph's Hospital, Phoenix, Arizona 85013, United States; Recruiting
Chanti Johnson-Smith, Email: chantijohnson-smith@dignityhealth.org
Lynn Ashby, Principal Investigator

Highlands Oncology Group Dept of Highlands Oncology Grp, Fayetteville, Arkansas 72703, United States; Recruiting
Tia Hesington, Phone: +1 479 872 8130, Email: thesington@hogonc.com
Joseph Thaddeus Beck, Principal Investigator

Novartis Investigative Site, Bologna, BO 40139, Italy; Withdrawn

Novartis Investigative Site, Barcelona, Catalunya 08003, Spain; Recruiting

Novartis Investigative Site, Barcelona, Catalunya 08036, Spain; Recruiting

Novartis Investigative Site, Hospitalet de LLobregat, Catalunya 08907, Spain; Recruiting

Northwestern University, Chicago, Illinois 60611, United States; Recruiting
Laura R. Sharp, Phone: 312-695-1382, Email: laura.sharp@northwestern.edu
Jeffrey J. Raizer, Principal Investigator

Novartis Investigative Site, Seoul, Korea 110 744, Korea, Republic of; Not yet recruiting

Novartis Investigative Site, Milano, MI 20133, Italy; Withdrawn

Novartis Investigative Site, Modena, MO 41100, Italy; Withdrawn

Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States; Recruiting
Allison C. Kamm, Phone: 617-632-3352, Email: akamm@mgh.harvard.edu
Patrick Y Wen, Principal Investigator

Novartis Investigative Site, Toronto, Ontario M5G 2M9, Canada; Recruiting

Novartis Investigative Site, Roma, RM 00168, Italy; Withdrawn

Novartis Investigative Site, North Adelaide, South Australia 5006, Australia; Not yet recruiting

Novartis Investigative Site, Torino, TO 10126, Italy; Withdrawn

MD Anderson Cancer Center/University of Texas, Houston, Texas 77030, United States; Recruiting
Be Pei, Phone: 713-745-5769, Email: bpei@mdanderson.org
John F. DeGroot, Principal Investigator

Novartis Investigative Site, Heidelberg, Victoria 3084, Australia; Recruiting

Novartis Investigative Site, Parkville, Victoria 3050, Australia; Recruiting

Additional Information

Starting date: February 2014
Last updated: May 15, 2015

Page last updated: August 23, 2015

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