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

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ClinicalTrials.gov Identifier: NCT01911325
Recruitment Status : Terminated (Review of safety and preliminary efficacy data showed marginal anti-tumor activity.)
First Posted : July 30, 2013
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Squamous Non-small Cell Lung Cancer Drug: Buparlisib Drug: Buparlisib matching placebo Drug: Docetaxel Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of Docetaxel With or Without Buparlisib as Second Line Therapy for Patients With Advanced or Metastatic Squamous Non-small Cell Lung Cancer
Study Start Date : October 2013
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: 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.
Drug: Buparlisib
Other Name: BKM120

Drug: Docetaxel
Experimental: 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.
Drug: Buparlisib
Other Name: BKM120

Drug: Docetaxel
Placebo Comparator: 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.
Drug: Buparlisib matching placebo
Drug: Docetaxel



Primary Outcome Measures :
  1. Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 [ Time Frame: Day 21 ]
    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

  2. Phase II: Progression Free Survival (PFS) [ Time Frame: After 70 PFS events have been observed at 9 months after patient enrollment ]
    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.


Secondary Outcome Measures :
  1. Number of patients with at least one adverse event. [ Time Frame: Up to 30 days after the last dose ]
  2. Number of patients with laboratory abnormalities. [ Time Frame: Up to 30 days after the last dose ]
  3. Overall Survival (OS) [ Time Frame: Treatment start (phase Ib)/randomization (phase II), every 6 weeks to the date of first document progression for up to 3 years ]
    Overall survival (OS) time is measured from the start of study drug to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact. Data will be collected post treatment every 6 weeks until approximately 75% of patients have reached the survival endpoint (Phase I + Phase II)

  4. Overall response rate (ORR) [ Time Frame: Every 6 weeks from randomization until first documented progression for up to 3 years ]
    Overall response is the number of participants who had a complete response (CR) or a partial response (PR) based on local investigator's assessment of RECIST 1.1 criteria.

  5. Time to response (ToR) [ Time Frame: Every 6 weeks from randomization until first documented progression for up to 3 years ]
    Time to overall response is defined as the time from the date of first drug intake in Phase Ib and from the date of randomization in Phase II to the date of first documented response.

  6. Duration of response (DR) [ Time Frame: Every 6 weeks from randomization until first documented progression for up to 3 years ]
    Duration of overall response is defined as the elapsed time between the date of first documented response and the following date of event defined as the first documented progression or death due to underlying cancer.

  7. Change in electrocardiogram (ECG) and cardiac imaging [ Time Frame: Up to 30 days after the last dose ]
  8. Changes in vital signs [ Time Frame: Up to 30 days after the last dose ]
  9. Shift in ECOG performance status [ Time Frame: Baseline, worst post-baseline result at day 1 of every cycle and at end of study treatment (3 years) ]
    cycle = 21 days; end of treatment is defined as 15 days after treatment discontinuation; There is no treatment duration as patients continue to receive drug till toxicity or they withdraw consent

  10. Change in Mood scales [ Time Frame: Up to 30 days after the last dose ]
  11. Time to definitive 10% deterioration in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30 [ Time Frame: Baseline, Every 6 weeks until disease progression for up to 3 years ]
    Date of event is defined as at least 10% relative to baseline worsening of the corresponding scale score or death due to any cause

  12. Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30 [ Time Frame: Baseline, Every 6 weeks until disease progression for up to 3 years ]
    Change in the domain scores

  13. Docetaxel and buparlisib plasma concentrations [ Time Frame: Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1 ]
  14. PFS Phase Ib [ Time Frame: at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years ]
    PFS as per RECIST 1.1



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01911325


Locations
United States, Arkansas
Highlands Oncology Group SC-1
Fayetteville, Arkansas, United States, 72703
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt
Tampa, Florida, United States, 33612
United States, Massachusetts
Reliant Medical Group Reliant Medical Group
Worcester, Massachusetts, United States, 01608
United States, Virginia
Virginia Oncology Associates Virginia Oncology Assoc. (2)
Norfolk, Virginia, United States, 23502
Belgium
Novartis Investigative Site
Charleroi, Belgium, 6000
Novartis Investigative Site
Mons, Belgium, 7000
France
Novartis Investigative Site
Creteil, France, 94000
Novartis Investigative Site
Saint Herblain cedex, France, 44805
Germany
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Mainz, Germany, 55131
Italy
Novartis Investigative Site
Monza, MB, Italy, 20900
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 05505
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 06351
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Sweden
Novartis Investigative Site
Stockholm, Sweden, 171 76
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01911325     History of Changes
Other Study ID Numbers: CBKM120D2205
2013-000833-11 ( EudraCT Number )
First Posted: July 30, 2013    Key Record Dates
Last Update Posted: August 14, 2018
Last Verified: August 2018

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Squamous non-small cell lung cancer
NSCLC
Docetaxel
Buparlisib
BKM120
Metastatic
Stage IIIb
Stage IV
PI3K inhibitor

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action