A Phase I Dose Escalation Study of BKM120 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

NCT01473901 | Completed Phase 1 FDA Drug

• 2 other identifiers: CBKM120E21012011-001157-87
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 8

Brief Summary

This clinical study will assess the doses of BKM120 appropriate for patients with newly diagnosed glioblastoma when given in combination with radiotherapy and temozolomide.

Conditions

Glioblastoma

Keywords

BKM120; temozolomide; glioblastoma multiforme; GBM; Newly diagnosed

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  Per DLT criteria as defined in protocol

  Concomitant phase (42 days), adjuvant phase cycle 1 (28-day cycle), adjuvant phase cycles 2 (28-day cycle)

Secondary Outcomes (5)

• No of participants with Adverse events based on abnormal laboratory results, abnormal electrocardiogram (ECG) findings

  Baseline, 30 days post the last BKM120 treatment

• Objective response rate (ORR)

  Baseline, 18 months after first BKM120 treatment

• Progression free survival (PFS)

  at 12 months and at 18 months

• Overall survival (OS)

  Until death or consent withdrawal

• Plasma concentration-time profiles and basic pharmacokinetic parameters of BKM120 and temozolomide (Cmax, tmas, AUC, half-life)

  baseline, Day 1, 8, 15, 28 in concomitant phase, Cycle 1 Day 1, 5 and Cycle 2 Day1, 5 at adjuvant phase (28-day per cycle)

Study Arms (2)

BKM120 + Temozolomide (Concomitant Phase)

EXPERIMENTAL

Cranial radiation: Days 1 - 5 every 7 days for 42 days60 Gy in 30 fractions; Temozolomide: 75 mg/m2 Daily, orally; BKM120: 0, or 40, or 60, or 80 mg/d Daily, orally or Days 1-5 every 7 days, orally

Drug: BKM120 + temozolomide

BKM120 + temozolomide with/without radiotherapy

EXPERIMENTAL

Adjuvant phase cycle 1: Temozolomide 150 mg/m2 - Days 1 - 5 every 28 days Daily; BKM120 60, or 80, or 100 mg/d; Adjuvant phase cycle 2+: Temozolomide 200\* mg/m2 - Day 1 \~ 5 every 28 days Daily BKM120 0, or 40, or 60, or 80 or 100 mg/d

Drug: BKM120 +temozolomide with/without radiotherapy

Interventions

BKM120 + temozolomide DRUG

The investigational drug, BKM120, will be supplied as 10-mg and 50-mg hard gelatin capsules. BKM120 will be administered on a once daily dosing schedule at a dose of 40 mg, or 60 mg, or 80 mg, or 100 mg (p.o.), in combination with the approved dosing of temozolomide and SoC delivery of cranial irradiation for GBM. The patient will be dosed with BKM120 on a flat scale of mg/day and the dose of BKM120 will not be adjusted to body weight or body surface area. Patients should not eat for 2 hours after the administration of BKM120. Temozolomide in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg capsules will be administered in combination with the investigational drug BKM120.

BKM120 + Temozolomide (Concomitant Phase)

BKM120 +temozolomide with/without radiotherapy DRUG

The investigational drug, BKM120, will be supplied as 10-mg and 50-mg hard gelatin capsules. BKM120 will be administered on a continuous once daily dosing schedule at a dose of 40 mg, or 60 mg, or 80 mg, or 100 mg (p.o.), in combination with the approved dosing of temozolomide and SoC delivery of cranial irradiation for GBM. The patient will be dosed with BKM120 on a flat scale of mg/day and the dose of BKM120 will not be adjusted to body weight or body surface area. Patients should not eat for 2 hours after the administration of BKM120. Temozolomide in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg capsules will be administered in combination with the investigational drug BKM120.

BKM120 + temozolomide with/without radiotherapy

Eligibility Criteria

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

You may qualify if:

• Patient is ≥ 18 years of age on the day of consent signature
• Patient with histologically demonstrated, previously untreated glioblastoma
• Patient may have received initial treatment for GBM as follows:
• For patients enrolled into Stage I, they must have received at least 75% of planned radiotherapy (60 Gy) with temozolomide treatment during the concomitant phase have documentation that the patient's absolute neutrophil count (ANC) is ≥ 1.5 x 109/L, platelet count is ≥ 100 x 109/L, and there was no CTC grade 2 or above nonhematological toxicity (except for alopecia, nausea, vomiting) during the concomitant phase treatment be within ≥ 4 weeks but ≤ 6 weeks following the completion of temozolomide in the concomitant phase
• For patients enrolled into Stage II, they must be within ≥ 2 weeks but ≤ 6 weeks after primary GBM resection/biopsy The patient must have recovered from the definitive surgical procedure for GBM
• Patient is able to be assessed by periodic dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scan
• Patient has Karnofsky performance status \>= 60
• Patient has adequate bone marrow and organ function

You may not qualify if:

• Patient has any tumor progression after definitive GBM resection/ biopsy, except for the transformation from previous low grade glioma. Patient with a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer)
• Patient has any of the following baseline mood disorders (not attributable to GBM) as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 12 in the PHQ- 9 or a cut-off of ≥ 15 in the GAD-7 mood scale for reasons not attributable to GBM; or selects a positive response of '1, 2, 3' to question number 9 regarding potential for suicidal thoughts or ideation in the PHQ-9 (independent of the total score of the PHQ-9)
• 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 (immediate risk of doing harm to others)
• Active severe personality disorders (defined according to DSM-IV). Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
• ≥ CTCAE grade 3 anxiety
• Patient who is concurrently using any other approved or investigational anti-neoplastic agent
• Patient who has undergone the following invasive procedures: Major surgical procedure, open biopsy or significant traumatic injury \< 14 days prior to starting study drug or has not recovered from side effects of such therapy, anticipation of need for invasive surgical procedure during the course of the study, biopsy within 7 days prior to starting study drug
• Patient has poorly controlled diabetes mellitus (HbA1c \> 8%)
• Patient is currently receiving increasing or chronic treatment with corticosteroids or another immunosuppressive agent
• Patient is currently receiving an enzyme inducing anti-epileptic drug. The patient must have discontinued EIAED therapy for at least two weeks prior to starting study drug. Non-enzyme inducing anti-epileptic medication is allowed, except those listed in the protocol

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Highlands Oncology Group Highlands Oncology

Fayetteville, Arkansas, 72703, United States

Location

Dana Farber Cancer Institute SC (1)

Boston, Massachusetts, 02215, United States

Location

University of Texas/MD Anderson Cancer Center MD Anderson DeGrout

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Hamilton, Ontario, L8V 5C2, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1Z6, Canada

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Related Publications (1)

• Wen PY, Rodon JA, Mason W, Beck JT, DeGroot J, Donnet V, Mills D, El-Hashimy M, Rosenthal M. Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. ESMO Open. 2020 Jul;5(4):e000673. doi: 10.1136/esmoopen-2020-000673.

  PMID: 32661186 DERIVED

Related Links

• Results for CBKM120E2101 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Glioblastoma

Interventions

NVP-BKM120; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: November 17, 2011
• Study Start: December 30, 2011
• Primary Completion: May 17, 2017
• Study Completion: May 17, 2017
• Last Updated: December 9, 2020

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); CA (2); US (3); AU (1)