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

Squamous Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01911325
• Other study ID #: CBKM120D2205
• Secondary ID: 2013-000833-11
• Status: Terminated
• Phase: Phase 1
• Start date: October 2013
• Est. completion date: August 2015

Study information

• Verified date: August 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Squamous Non-small Cell Lung Cancer

Intervention

Drug:
• Buparlisib

• Buparlisib matching placebo

• Docetaxel

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Mons
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Saint Herblain cedex
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Mainz
Italy	Novartis Investigative Site	Monza	MB
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Spain	Novartis Investigative Site	Barcelona	Catalunya
Sweden	Novartis Investigative Site	Stockholm
United States	Highlands Oncology Group SC-1	Fayetteville	Arkansas
United States	Virginia Oncology Associates Virginia Oncology Assoc. (2)	Norfolk	Virginia
United States	H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt	Tampa	Florida
United States	Reliant Medical Group Reliant Medical Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Number of patients with at least one adverse event.		Up to 30 days after the last dose
Secondary	Number of patients with laboratory abnormalities.		Up to 30 days after the last dose
Secondary	Overall Survival (OS)	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)	Treatment start (phase Ib)/randomization (phase II), every 6 weeks to the date of first document progression for up to 3 years
Secondary	Overall response rate (ORR)	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.	Every 6 weeks from randomization until first documented progression for up to 3 years
Secondary	Time to response (ToR)	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.	Every 6 weeks from randomization until first documented progression for up to 3 years
Secondary	Duration of response (DR)	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.	Every 6 weeks from randomization until first documented progression for up to 3 years
Secondary	Change in electrocardiogram (ECG) and cardiac imaging		Up to 30 days after the last dose
Secondary	Changes in vital signs		Up to 30 days after the last dose
Secondary	Shift in ECOG performance status	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	Baseline, worst post-baseline result at day 1 of every cycle and at end of study treatment (3 years)
Secondary	Change in Mood scales		Up to 30 days after the last dose
Secondary	Time to definitive 10% deterioration in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30	Date of event is defined as at least 10% relative to baseline worsening of the corresponding scale score or death due to any cause	Baseline, Every 6 weeks until disease progression for up to 3 years
Secondary	Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30	Change in the domain scores	Baseline, Every 6 weeks until disease progression for up to 3 years
Secondary	Docetaxel and buparlisib plasma concentrations		Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1
Secondary	PFS Phase Ib	PFS as per RECIST 1.1	at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years