Head and Neck Squamous Cell Carcinoma (HNSCC) MedDRA version: 21.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Buparlisib
Product Code: [NA]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: buparlisib
CAS Number: 944396-07-0
Current Sponsor code: AN2925
Concentration unit: mg milligram(s)
Sponsors
Adlai Nortye USA Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Aged =18yo. Able to provide ICFobtained before any study related activities. PT has histologically and/or cytologically-confirmed HNSCC. Patient has archival or new tumor tissue for the analysis of biomarkers. A tumor block (preferred) or a minimum of 12 (15 recommended) unstained slides to be provided. Enrollment in the study is contingent on confirmation of an adequate amount of tumor tissue. Patients progressing following treatment with an anti PD 1/anti PD L1 therapy are encouraged to have a new tumor biopsy for biomarker analysis. PT has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease: PDLl/PD1 therapy alone for metastatic (monotherapy) disease PDL1/PD1 in combination with chemotherapy for metastatic and recurrent disease PDL1/PD1 used for metastatic disease, after or prior to receiving a platinum agent for locally advanced or metastatic disease. PT has received no more than two prior lines of systemic treatment for HNSCC (single agent chemotherapy used as a radiosensitizer is not counted as a prior line of therapy). PT has measurable disease as determined per RECIST version 1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a four-week period since radiotherapy completion is required. PT has adequate bone marrow function and organ function as shown by the following: ANC=1.5x109/L. Hemoglobin=9g/dL (which may be reached by transfusion). Platelets=100x109/L (which may be reached by transfusion). International normalized ratio (INR) = 1.5. Ca(corrected for serum albumin) within normal limits (WNL) or = grade 1 severity according to NCI-CTCAE version 5.0 if judged clinically not significant by the Investigator. Patients concomitantly taking bisphosphonates or denosumab for calcium correction are eligible. AST and ALT=1.5 xULNor 30 mL/min. I. Haemoglobin A1c (glycosylated hemoglobin; HbA1c) =8%. Patient has Eastern Cooperative Oncology Group (ECOG) performance status =1. Patient is able to swallow and retain oral medication. Patients able to swallow oral medication but mostly self-nourished through gastric or jejunal feeding tube are eligible. Patients must apply highly effective contraception during and throughout the study, as well after the final dose of study treatment, as detailed below: Men should use an effective method of contraception and not father a child during the study and for the six-month period after treatment. Men are recommended to seek advice on conservation of sperm prior to treatment with paclitaxel as per product label. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use a highly effective contraceptive during the study and for at least four weeks after the final dose of study treatmen
Exclusion criteria
Exclusion criteria: Pt has received previous treatment with any PKB/AKT, mammalian target of rapamycin (mTOR) inhibitors, or PI3K pathway inhibitors.Pt received treatment with taxane as part prior treatment for metastatic disease. Pt has symptomatic CNS metastases.Pts with asymptomatic CNS metastases may participate in study. Pt must have completed any prior local treat for CNS metastases=28 d prior to start study treatment (including radiotherapy) and must be on a stable low dose corticosteroid therapy. Radiosurgery must have been completed at least 14 d prior to start study treatment. Pt has received wide field radiotherapy=4w or limited field radiation for palliation=2 w prior to starting study treatment or who have AE which have not recovered to grade1 or better from previous chemotherapy treat. Pt has grade=2 neuropathy, colitis, pneumonitis, elevated HbA1C, and uncontrolled endocrinopathies from previous treatment. Pt has had major surgery within 14 d prior to starting treatment or has not recovered from major side effects. Pt is currently receiving increasing or chronic treatment (>5d) with corticosteroids or immunosuppressive agent. following uses of corticosteroids are permitted: single doses; standard premedication for paclitaxel, topical applications, inhaled sprays, eye drops,local injections,or450 msec for males and 470 msec for females, on the screening ECG, Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment. Pt has impairment of GI function or GI disease that may significantly alter the absorption of study treatment. 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 active severe personality disorders are not eligible. Pt has other prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, early gastric or GI cancer resected completely by endoscopy procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is as follows: • To assess the overall survival (OS) of buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with refractory, recurrent, or metastatic HNSCC.;Secondary Objective: The secondary objectives of the study are as follows: • To evaluate additional efficacy parameters: progression free survival (PFS), ORR, and DoR, by the Investigator and Independent Radiological Review Committee (IRRC). • To evaluate efficacy parameters in subgroups of patients defined by the randomization strata. • To assess the effect of buparlisib in combination with paclitaxel on patient's symptoms and health-related quality of life (HRQoL). • To assess biomarkers of response to buparlisib in combination with paclitaxel. • To assess the pharmacokinetics (PK) of buparlisib in combination with paclitaxel.;Primary end point(s): The primary endpoint of this study is OS for the entire (Intent-to-Treat [ITT]) population of patients. The interim endpoint of the study is ORR on a subset of patients with at least six months follow up at the time the last patient is enrolled;Timepoint(s) of evaluation of this end point: The primary statistical analysis of the study will be based on OS data from all patients once 383 events (deaths) have occurred. This analysis is expected to occur when all patients have either discontinued from the study or been followed for a minimum of 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are as follows: Efficacy: • PFS • Overall response rate (ORR) • Duration of response (DoR) • Change from baseline in the global health status/Quality of life (QOL) and pain scale scores of the EORTC QLQ-C30, respectively. • Time to definitive 10% deterioration in the global health status/QOL and pain scale scores of the EORTC QLQ-C30, respectively. • EQ-5D-5L • Biomarkers; Safety: • AEs • Clinical laboratory tests • PHQ-9 • GAD-7;Timepoint(s) of evaluation of this end point: All secondary analyses will be reported by treatment arm and analyses will be based on the ITT Population. PFS and DoR will be analyzed using the same methods as for the primary endpoint of OS. ORR will be analyzed using a Cochran-Mantel-Haenszel chi-square test with randomization factors as the strata. Safety summaries and analyses will be performed on the Safety population. Descriptive statistics will be presented to summarize the safety data.; All secondary analyses will be reported by treatment arm and analyses will be based on the ITT Population. PFS and DoR will be analyzed using the same methods as for the primary endpoint of OS. ORR will be analyzed using a Cochran-Mantel-Haenszel chi-square test with randomization factors as the strata. Safety summaries and analyses will be perfor | — |
Countries
Australia, Belgium, Canada, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactKevin Dreyer
Adlai Nortye USA Inc.,
Outcome results
None listed