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

NCT01911325 | Terminated Phase 1 DMC

• 2 other identifiers: CBKM120D22052013-000833-11
• Study Type: interventional
• Target: 27
• Locations: 8 countries
• Sites: 16

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.

Conditions

Squamous Non-small Cell Lung Cancer

Keywords

Squamous non-small cell lung cancer; NSCLC; Docetaxel; Buparlisib; BKM120; Metastatic; Stage IIIb; Stage IV; PI3K inhibitor

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1

  To determine the maximum tolerated dose/recommended phase ll dose (MTD/RP2D) of buparlisib in combination with docetaxel by assessing the incidence of DLTs in Cycle 1; Cycle 1 = 21 days

  Day 21

• Phase II: Progression Free Survival (PFS)

  PFS as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. To estimate the treatment effect of docetaxel and buparlisib or placebo on PFS in patients with advanced or metastatic squamous NSCLC.

  After 70 PFS events have been observed at 9 months after patient enrollment

Secondary Outcomes (14)

• Number of patients with at least one adverse event.

  Up to 30 days after the last dose

• Number of patients with laboratory abnormalities.

  Up to 30 days after the last dose

• Overall Survival (OS)

  Treatment start (phase Ib)/randomization (phase II), every 6 weeks to the date of first document progression for up to 3 years

• Overall response rate (ORR)

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

• Time to response (ToR)

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

Study Arms (3)

Phase Ib: Buparlisib + docetaxel

EXPERIMENTAL

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.

Drug: Buparlisib; Drug: Docetaxel

Phase II: Buparlisib + docetaxel

EXPERIMENTAL

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.

Drug: Buparlisib; Drug: Docetaxel

Phase II: Placebo + docetaxel

PLACEBO COMPARATOR

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.

Drug: Buparlisib matching placebo; Drug: Docetaxel

Interventions

Buparlisib DRUG

Also known as: BKM120

Phase II: Buparlisib + docetaxel; Phase Ib: Buparlisib + docetaxel

Buparlisib matching placebo DRUG

Phase II: Placebo + docetaxel

Docetaxel DRUG

Phase II: Buparlisib + docetaxel; Phase II: Placebo + docetaxel; Phase Ib: Buparlisib + docetaxel

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (16)

Highlands Oncology Group SC-1

Fayetteville, Arkansas, 72703, United States

Location

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

Tampa, Florida, 33612, United States

Location

Reliant Medical Group Reliant Medical Group

Worcester, Massachusetts, 01608, United States

Location

Virginia Oncology Associates Virginia Oncology Assoc. (2)

Norfolk, Virginia, 23502, United States

Location

Novartis Investigative Site

Charleroi, 6000, Belgium

Location

Novartis Investigative Site

Mons, 7000, Belgium

Location

Novartis Investigative Site

Créteil, 94000, France

Location

Novartis Investigative Site

Saint-Herblain, 44805, France

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Stockholm, 171 76, Sweden

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

NVP-BKM120; Docetaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: July 30, 2013
• Study Start: October 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 14, 2018

Record last verified: 2018-08

Locations

FR (2); IT (1); DE (3); US (4); BE (2); KR (2); ES (1); SE (1)