E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
recurrent or metastatic head and neck cancer squamous cell carcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
recurrent or metastatic head and neck cancer squamous cell carcinoma |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 estimate the efficacy of buparlisib in combination with paclitaxel |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of buparlisib in combination with paclitaxel in this patient population
To evaluate additional efficacy parameters
To assess the effect of buparlisib in combination with paclitaxel on patient's symptoms and health-related qualoty of life (HRQoL)
To characterize the pharmacokinetics of buparlisib BKM120 given in combination with paclitaxel |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patient has histologically/cytologically-confirmed HNSCC.
•Patient has archival or fresh new tumor tissue for the analysis of PI3K-related biomarkers. One tumor block (preferred) or a minimum of 15 12 (15 recommended) unstained slides to be provided. Enrollment in the study is contingent on confirmation the central laboratory confirming receipt of an adequate amount of tumor tissue.
•Patients with recurrent or metastatic disease resistant to platinum-based chemotherapy (defined as progression while on or after a platinum-based chemotherapy given in the recurrent/metastatic setting). Pretreatment with cetuximab is allowed
•Measurable disease as determined by per RECIST criteria v1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a 4 week period since radiotherapy completion is required
•Adequate bone marrow function and organ function
•ECOG Performance Status ≤ 1
see protocol for other criteria |
|
E.4 | Principal exclusion criteria |
•Patient has received previous treatment with any AKT, mTOR inhibitors or PI3K pathway inhibitors;
•Patient treated with more than one prior chemotherapy regimen for recurrent/metastatic disease
•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) and must have stable low dose of corticosteroid therapy;
•Patient has not recovered to ≤ grade 1 (except alopecia) from related side effects of any prior antineoplastic therapy
•Patient has any of the following cardiac abnormalities:symptomatic congestive heart failure, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO); myocardial infarction ≤ 6 months prior to enrolment, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, QTcF > 480 msec on the screening ECG (using the QTcF formula);
see protocol for other criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at 4 weeks after study treatment start and every 6 weeks afterwards |
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E.5.2 | Secondary end point(s) |
1: Overall Survival
2: Safety and Tolerability
3: Overall Response Rate (ORR)
4: Time to Response (TTR)
5: Disease Control Rate (DCR)
6: Duration of Response (DoR)
7 : PK parameters including Cmax, AUCtau
8: Change from baseline in the global health status/QOL and pain scale scores of the EORTC QLQ-C30 and QLQ-HN35
9: Time to definitive 10% deterioration in the global health status/QOL (quality of life)
10: Pain scale scores of the EORTC QLQ-C30 and QLQ-HN35 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For endpoint 1: every 3 months for 2 years
For endpoint 2: on an ongoing basis for a maximum of 2 years
For endpoints 3, 4, 5 & 6: at 4 weeks after study treatment start and every 6 weeks afterwards until 2 years
For endpoint 7 : depending on full PK and sparse PK (fore details see protocol)
For endpoints 8, 9 & 10: baseline and every 6 weeks after randomization for 2 years |
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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 | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | No |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Australia |
Canada |
France |
Germany |
Hungary |
India |
Ireland |
Italy |
Japan |
Korea, Republic of |
Poland |
Russian Federation |
Spain |
Switzerland |
Taiwan |
Thailand |
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
|
End of Study will be declared when the study is terminated early or at the latest occurrence of:
• All patients have completed the safety follow-up period (30 days after treatment discontinuation) or
• At least 112 deaths have been observed.
|
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 23 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 23 |