Squamous Non-small Cell Lung CancerPhase 1NCT01911325
Phase II Study of Buparlisib + Docetaxel in Advanced or Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) Patients
A Phase 1 study testing Buparlisib and Docetaxel in people with Squamous Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 16 sites in 8 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Non-small Cell Lung Cancer
- What is being tested?
- Buparlisib and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 16 sitesin 8 countries
- Study dates
- Oct 2013to Aug 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 8 countries.
16 sites in 8 countries
United States4 sites
Highlands Oncology Group SC-1
Fayetteville, Arkansas, 72703
Virginia Oncology Associates Virginia Oncology Assoc. (2)
Norfolk, Virginia, 23502
H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt
Tampa, Florida, 33612
Reliant Medical Group Reliant Medical Group
Worcester, Massachusetts, 01608
Germany3 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Mainz, 55131
Belgium2 sites
Novartis Investigative Site
Charleroi, 6000
Novartis Investigative Site
Mons, 7000
France2 sites
Novartis Investigative Site
Créteil, 94000
Novartis Investigative Site
Saint-Herblain, 44805
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 05505
Novartis Investigative Site
Seoul, Korea, 06351
About this study
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
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.
Read the 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
- Being tested
- Buparlisib, Buparlisib matching placebo, Docetaxel
- Keywords
- Squamous non-small cell lung cancer, NSCLC, Docetaxel, Buparlisib, BKM120, Metastatic, Stage IIIb, Stage IV, PI3K inhibitor
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuparlisibDrug
Also called BKM120
Buparlisib matching placeboDrug
DocetaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Buparlisib matching placebo; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: Up to 30 days after the last dose
Number of patients with laboratory abnormalities.
Measured: Up to 30 days after the last dose
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)
Measured: 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)
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.
Measured: Every 6 weeks from randomization until first documented progression for up to 3 years
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.
Measured: Every 6 weeks from randomization until first documented progression for up to 3 years
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.
Measured: Every 6 weeks from randomization until first documented progression for up to 3 years
Change in electrocardiogram (ECG) and cardiac imaging
Measured: Up to 30 days after the last dose
Changes in vital signs
Measured: Up to 30 days after the last dose
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
Measured: Baseline, worst post-baseline result at day 1 of every cycle and at end of study treatment (3 years)
Change in Mood scales
Measured: Up to 30 days after the last dose
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
Measured: Baseline, Every 6 weeks until disease progression for up to 3 years
Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
Change in the domain scores
Measured: Baseline, Every 6 weeks until disease progression for up to 3 years
Docetaxel and buparlisib plasma concentrations
Measured: Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1
PFS Phase Ib
PFS as per RECIST 1.1
Measured: at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study startOct 2013
- Primary completionAug 2015
- Study completionAug 2015
Why it stopped: Review of safety and preliminary efficacy data showed marginal anti-tumor activity.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01911325
- Sponsor's protocol ID
- CBKM120D2205
- Other IDs
- 2013-000833-11
- Status last verified
- Aug 2018
- First submitted
- 16 May 2013
- Last updated
- 14 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01911325
- Acronym / sponsor ID
- CBKM120D2205
- Conditions
- Squamous Non-small Cell Lung Cancer
- Keywords
- Squamous non-small cell lung cancer, NSCLC, Docetaxel, Buparlisib, BKM120, Metastatic, Stage IIIb, Stage IV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Review of safety and preliminary efficacy data showed marginal anti-tumor activity.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 30 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase Ib: Buparlisib + docetaxel | Experimental | Drug: Buparlisib, Drug: DocetaxelBuparlisib (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. |
| Phase II: Buparlisib + docetaxel | Experimental | Drug: Buparlisib, Drug: DocetaxelBuparlisib 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. |
| Phase II: Placebo + docetaxel | Placebo comparator | Drug: Buparlisib matching placebo, Drug: DocetaxelBuparlisib matching placebo oral once daily to be tested in combination with docetaxel every three week i.v. infusion: 75 mg/m2 as per label. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BuparlisibAlso: BKM120 | Drug | 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 |
Primary outcome
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
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.
14 secondary outcomes
Number of patients with at least one adverse event.
Time frame: Up to 30 days after the last dose
Number of patients with laboratory abnormalities.
Time frame: Up to 30 days after the last dose
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 response rate (ORR)
Time frame: Every 6 weeks from randomization until first documented progression for up to 3 years
Time to response (ToR)
Time frame: Every 6 weeks from randomization until first documented progression for up to 3 years
Duration of response (DR)
Time frame: Every 6 weeks from randomization until first documented progression for up to 3 years
Change in electrocardiogram (ECG) and cardiac imaging
Time frame: Up to 30 days after the last dose
Changes in vital signs
Time frame: Up to 30 days after the last dose
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)
Change in Mood scales
Time frame: Up to 30 days after the last dose
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
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
Docetaxel and buparlisib plasma concentrations
Time frame: Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1
PFS Phase Ib
Time frame: at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years
Results and safety
The study was stopped early (reason given: Review of safety and preliminary efficacy data showed marginal anti-tumor activity.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
16 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Buparlisib and Docetaxel in people with Squamous Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 16 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Germany, Belgium, France, South Korea and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Review of safety and preliminary efficacy data showed marginal anti-tumor activity.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (time frame: Day 21). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2018.