Phase II Study of Buparlisib + Docetaxel in Advanced or Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) Patients

NCT ID: NCT01911325

Last Updated: 2018-08-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-08-31

Brief Summary

This is a multi-center, open-label Phase Ib dose escalation part followed by a randomized double-blinded placebo controlled Phase II part.

The Phase Ib part will determine the Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of buparlisib in combination with docetaxel. Subsequently the MTD/RP2D will be investigated in a Phase II randomized trial in patients with advanced or metastatic squamous NSCLC.

Detailed Description

Based on an overall review of safety and preliminary efficacy data done on 01-Dec-2014 showing marginal anti-tumor activity and newly emerged treatment options, a decision was taken to stop further development of this combination in patients with advanced or metastatic squamous NSCLC and Phase II of the study was not conducted.

Conditions

Squamous Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Phase Ib: Buparlisib + docetaxel

Buparlisib (BKM120) oral once daily: 80 mg and 100 mg dose levels to be tested in the dose escalation part of the trial in combination with docetaxel every three week intravenous (i.v.) infusion: 75 mg/m2 as per label.

Group Type: EXPERIMENTAL

Buparlisib

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Phase II: Buparlisib + docetaxel

Buparlisib oral once daily: MTD/RP2D mg to be tested in combination with docetaxel every three week i.v. infusion: 75 mg/m2 as per label.

Group Type: EXPERIMENTAL

Buparlisib

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Phase II: Placebo + docetaxel

Buparlisib matching placebo oral once daily to be tested in combination with docetaxel every three week i.v. infusion: 75 mg/m2 as per label.

Group Type: PLACEBO_COMPARATOR

Buparlisib matching placebo

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Interventions

Buparlisib

Intervention Type: DRUG

Buparlisib matching placebo

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Other Intervention Names

BKM120

Eligibility Criteria

Inclusion Criteria

• Patient is an adult ≥ 18 years old at the time of informed consent
• Patient has histologically and/or cytologically confirmed diagnosis of squamous NSCLC. Diagnosis of mixed squamous and non-squamous or adenosquamous NSCLC will be acceptable for enrollment.
• Patient has received one prior approved regimen of platinum-based chemotherapy (excluding a docetaxel-containing regimen) for advanced or metastatic (Stage IIIb or Stage IV) squamous NSCLC, followed by disease progression. A drug provided as maintenance therapy following cytotoxic chemotherapy will be considered to be part of that regimen.

Note: Patients who received paclitaxel therapy are eligible for this trial. •Patient has adequate tumor tissue (either archival or new tumor biopsy) for the analysis of PI3K-related biomarkers.

Enrollment in the Phase II part of the study is contingent on the central laboratory confirming receipt of an adequate amount of tissue including sufficient DNA for analysis.

•Patient has measurable or non-measurable disease according to RECIST version 1.1 criteria.

Phase II only: Patient must have at least one measurable lesion as per RECIST criteria.

• Patient has an ECOG performance status ≤ 1
• Patient has adequate bone marrow and organ function

Exclusion Criteria

• Patient has received previous treatment with a PI3K or AKT inhibitor
• Patient has symptomatic Central Nervous System (CNS) metastases Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed prior local treatment, if any, for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery, or ≥ 14 days for stereotactic radiosurgery).
• Patient has a score ≥ 12 on the PHQ-9 questionnaire.
• Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9).
• Patient has a GAD-7 mood scale score ≥ 15.
• 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 or patients with active severe personality disorders.
• Patient has ≥ CTCAE grade 3 anxiety

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Highlands Oncology Group SC-1

Fayetteville, Arkansas, United States

H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt

Tampa, Florida, United States

Reliant Medical Group Reliant Medical Group

Worcester, Massachusetts, United States

Virginia Oncology Associates Virginia Oncology Assoc. (2)

Norfolk, Virginia, United States

Novartis Investigative Site

Charleroi, , Belgium

Novartis Investigative Site

Mons, , Belgium

Novartis Investigative Site

Créteil, , France

Novartis Investigative Site

Saint-Herblain, , France

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Mainz, , Germany

Novartis Investigative Site

Monza, MB, Italy

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Stockholm, , Sweden

Countries

United States; Belgium; France; Germany; Italy; South Korea; Spain; Sweden

Other Identifiers

2013-000833-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBKM120D2205

Identifier Type: -

Identifier Source: org_study_id