E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
squamous non small cell lung cancer |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001254 |
E.1.2 | Term | Adenosquamous cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001253 |
E.1.2 | Term | Adenosquamous cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the MTD/RP2D of buparlisib when administered orally in combination with every-3-week carboplatin and paclitaxel to adult patients with previously untreated Stage IIIb (with malignant pleural or pericardial effusion) or Stage IV NSCLC of
squamous histology |
|
E.2.2 | Secondary objectives of the trial |
- Assess safety and tolerability
- Assess preliminary activity |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-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 archival or fresh tumor tissue for the exploratory
analysis of biomarkers related to sensitivity to PI3K
inhibitors.
- Tumor is Stage IV or Stage IIIb (with malignant pleural or pericardial effusion) at the time of signed informed consent (UICC/AJCC version 7)
-Patient has measurable or non-measurable disease according to
RECIST v1.1 criteria (for the Phase II portion, the patient must have measurable disease according to RECIST 1.1 criteria)
- Patient has an Eastern Cooperative Oncology
Group (ECOG) performance status ≤ 1 that the investigator
believes is stable at the time of screening
- Patient has adequate bone marrow and organ function |
|
E.4 | Principal exclusion criteria |
- Patient has received any prior systemic therapies for metastatic NSCLC. Study treatment in this clinical trial must be the patient’s first systemic treatment for metastatic NSCLC. Patients are eligible if they received neo-adjuvant or adjuvant systemic therapy followed by a disease-free interval exceeding 12 months.
- Patient has symptomatic CNS metastases [patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS
metastases ≥ 28 days prior to the start of study treatment
(including radiotherapy and/or surgery, or ≥14 days for
stereotactic radiosurgery)].
- Patient is currently receiving warfarin or other coumadin derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
- Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to
randomization is allowed.
- 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 (e.g. risk of doing harm to self or others) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients
with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug
- Patient has ≥ CTCAE grade 3 anxiety
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL) -Patient who does not apply highly effective
contraception during the study and through the duration as
defined below after the final dose of study treatment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Number of Total Dose-limiting Toxicity (DLT) during dose escalation to determine Maximum Tolerated Dose (MTD)
- Progression Free Survival (PFS) as measured using RECIST 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint for DLT: Cycle 1 (21 days)
Timepoint for PFS: at randomization, every 6 weeks to the date of first document progression for up to 3 years |
|
E.5.2 | Secondary end point(s) |
1. Number of participants with best overall response rate (ORR) according to RECIST
2. Overall Survival Time
3. Time to overall response
4. Overall Safety and Tolerability of buparlisib (BKM120)
5. Change from baseline in QoL measured bu the functional assessment of EORTC QLQ-C-30 and lung cancer module (QLQ-LC-13)
6. Time to deterioration by the functional assessment of EORTC QLQ-C-30 and lung cancer module (QLQ-LC-13)
7. Buparlisib concentrations
8. Duration of overall response |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints 1, 2, 3 and 8: every 6 weeks from randomization until first documented progression for up to 3 years
Endpoint 4: untill 30 days after last dose
Endpoints 5 and 6: screening, every 6 weeks until disease progression for up to 3 years
Endpoint 7: cycle 1 day 8 and day 15, cycle 2 day 1, cycle 7-cycle n day 1 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
dose finding phase Ib study |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Colombia |
Czech Republic |
Finland |
France |
Germany |
Hungary |
Italy |
Japan |
Netherlands |
Norway |
Peru |
Russian Federation |
South Africa |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
If the Phase II part is not initiated, the study will end when all patients have discontinued treatment and completed the safety follow up.
If the Phase II part is initiated, the study will end when terminated early or at the latest occurence of:
• at least 1 year since the data cut-off date for the primary analysis and all patients have completed the safety follow-up period
• at least 75% of deaths |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |