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.
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.
Brief Title
Phase II Study of Buparlisib + Docetaxel in Advanced or Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) Patients
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Squamous Non-small Cell Lung Cancer
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Squamous non-small cell lung cancer
NSCLC
Docetaxel
Buparlisib
BKM120
Metastatic
Stage IIIb
Stage IV
PI3K inhibitor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01911325
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CBKM120D2205
Overall Status
Terminated
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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
Outcome Measure
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
Outcome Time Frame
Day 21
Outcome Description
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.
Outcome Measure
Phase II: Progression Free Survival (PFS)
Outcome Time Frame
After 70 PFS events have been observed at 9 months after patient enrollment
Secondary Ids
Secondary Id
2013-000833-11
Secondary Outcomes
Outcome Time Frame
Up to 30 days after the last dose
Outcome Measure
Number of patients with at least one adverse event.
Outcome Time Frame
Up to 30 days after the last dose
Outcome Measure
Number of patients with laboratory abnormalities.
Outcome Description
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)
Outcome Time Frame
Treatment start (phase Ib)/randomization (phase II), every 6 weeks to the date of first document progression for up to 3 years
Outcome Measure
Overall Survival (OS)
Outcome Description
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.
Outcome Time Frame
Every 6 weeks from randomization until first documented progression for up to 3 years
Outcome Measure
Overall response rate (ORR)
Outcome Description
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.
Outcome Time Frame
Every 6 weeks from randomization until first documented progression for up to 3 years
Outcome Measure
Time to response (ToR)
Outcome Description
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.
Outcome Time Frame
Every 6 weeks from randomization until first documented progression for up to 3 years
Outcome Measure
Duration of response (DR)
Outcome Time Frame
Up to 30 days after the last dose
Outcome Measure
Change in electrocardiogram (ECG) and cardiac imaging
Outcome Time Frame
Up to 30 days after the last dose
Outcome Measure
Changes in vital signs
Outcome Description
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
Outcome Time Frame
Baseline, worst post-baseline result at day 1 of every cycle and at end of study treatment (3 years)
Outcome Measure
Shift in ECOG performance status
Outcome Time Frame
Up to 30 days after the last dose
Outcome Measure
Change in Mood scales
Outcome Description
Date of event is defined as at least 10% relative to baseline worsening of the corresponding scale score or death due to any cause
Outcome Time Frame
Baseline, Every 6 weeks until disease progression for up to 3 years
Outcome Measure
Time to definitive 10% deterioration in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
Outcome Description
Change in the domain scores
Outcome Time Frame
Baseline, Every 6 weeks until disease progression for up to 3 years
Outcome Measure
Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
Outcome Time Frame
Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1
Outcome Measure
Docetaxel and buparlisib plasma concentrations
Outcome Description
PFS as per RECIST 1.1
Outcome Time Frame
at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years
Outcome Measure
PFS Phase Ib
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Missak Haingentz
Investigator Email
Investigator Phone