Safety and Efficacy of Buparlisib (BKM120) in Patients With Untreated Squamous Non-small Cell Lung Cancer

NCT01820325 | Terminated Phase 1 DMC

• 2 other identifiers: CBKM120D22042012-005541-21
• Study Type: interventional
• Target: 6
• Locations: 5 countries
• Sites: 7

Brief Summary

The Phase Ib part of the study aimed to determine the maximum tolerated dose/recommended Phase II dose (MTD/RP2D) of once daily buparlisib in combination with every-three-week carboplatin and paclitaxel in patients with previously untreated metastatic squamous NSCLC. The purpose of the Phase II portion of the study was to assess the treatment effect of adding buparlisib versus buparlisib-matching placebo to every-three-week carboplatin and paclitaxel on progression free survival (PFS) in patients with previously untreated metastatic squamous NSCLC.

Conditions

Non-Small Cell Lunch Cancer

Keywords

Squamous non-small cell lung cancer; NSCLC; stage IV; BKM120

Outcome Measures

Primary Outcomes (2)

• Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)

  Determine the MTD and/or RP2D of daily buparlisib in combination with paclitaxel and carboplatin in patients with advanced or metastatic squamous NSCLC.

  Cycle 1 (21 days)

• Progression Free Survival (PFS) as measured using RECIST 1.1

  Progression-free survival is defined as the time from randomization to the date of the first documented progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was contructed.

  Randomization, every 6 weeks to the date of first document progression for up to 3 years

Secondary Outcomes (9)

• Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)

  Every 6 weeks from randomization until first documented progression for up to 3 years

• Overall Survival Time

  Every 6 weeks from randomization until first documented progression for up to 3 years

• Time to overall response

  Every 6 weeks from randomization until first documented progression for up to 3 years

• The Overall Safety and Tolerability of buparlisib (BKM120)

  Screening, Until 30 days after last dose

• Change From Baseline in Quality of Life Measured by the Functional Assessment of EORTC QLQ- C-30 and lung cancer module (QLQ-LC-13)

  Screening, Every 6 weeks until disease progression for up to 3 years

Study Arms (2)

Buparlisib + Carboplatin + Paclitaxel

EXPERIMENTAL

Carboplatin and paclitaxel plus buparlisib for up to 6 cycles, followed by blinded buparlisib maintenance

Drug: Buparlisib; Drug: Carboplatin; Drug: Paclitaxel

Placebo + Carboplatin + Paclitaxel

PLACEBO COMPARATOR

Carboplatin and paclitaxel plus buparlisib-matching placebo for up to 6 cycles, followed by blinded placebo maintenance

Drug: Buparlisib placebo; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Buparlisib DRUG

Also known as: BKM120

Buparlisib + Carboplatin + Paclitaxel

Buparlisib placebo DRUG

Placebo + Carboplatin + Paclitaxel

Placebo + Carboplatin + Paclitaxel

Carboplatin DRUG

Buparlisib + Carboplatin + Paclitaxel; Placebo + Carboplatin + Paclitaxel

Paclitaxel DRUG

Buparlisib + Carboplatin + Paclitaxel; Placebo + Carboplatin + Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Patient has histologically and/or cytologically confirmed diagnosis of squamous NSCLC. Diagnosis of mixed squamous with a squamous component will be acceptable for enrollment.
• Patient has archival or new tumor tissue for the analysis of PI3K biomarkers
• Tumor is Stage IV at the time of signed informed consent (UICC/AJCC version 7)
• Patient has measurable or non-measurable disease according to RECIST v1.1 criteria
• For the Phase II portion, the patient must have measurable disease according to RECIST 1.1 criteria
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 that the investigator believes is stable at the time of screening
• Patient has adequate bone marrow and organ function

You may not qualify if:

• Patient has received any prior systemic therapies for metastatic NSCLC. Study treatment in this clinical trial must be the patient's first systemic treatment for metastatic NSCLC. Patients are eligible if they received neo-adjuvant or adjuvant systemic therapy followed by a disease-free interval exceeding 12 months.
• Patient has symptomatic CNS metastases
• Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery, or ≥14 days for stereotactic radiosurgery).
• Patient is currently receiving warfarin or other coumadin derived anticoagulant 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 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 has a 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) are not eligible. 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
• Patient has ≥ CTCAE grade 3 anxiety
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL)
• Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Northwest Cancer Specialists Compass Oncology -BKM

Portland, Oregon, 97210, United States

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1Z6, Canada

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Related Publications (1)

• Vansteenkiste JF, Canon JL, De Braud F, Grossi F, De Pas T, Gray JE, Su WC, Felip E, Yoshioka H, Gridelli C, Dy GK, Thongprasert S, Reck M, Aimone P, Vidam GA, Roussou P, Wang YA, Di Tomaso E, Soria JC. Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study. J Thorac Oncol. 2015 Sep;10(9):1319-1327. doi: 10.1097/JTO.0000000000000607.

  PMID: 26098748 DERIVED

MeSH Terms

Interventions

NVP-BKM120; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: March 28, 2013
• Study Start: September 9, 2013
• Primary Completion: June 18, 2014
• Study Completion: June 18, 2014
• Last Updated: October 11, 2018

Record last verified: 2018-10

Locations

CA (1); US (2); ES (2); DE (1); IT (1)