Head and neck squamous cell carcinoma
Conditions
Interventions
arm A:Daily buparlisib (100 mg) in combination with weekly paclitaxel (80 mg/m2)
arm B:Weekly paclitaxel (80 mg/m2) alone
Sponsors
Kanmuri Kazuhiro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged >=18 years old. 2. Able to provide informed consent obtained before any study related activities and according to local guidelines. 3. Patient has histologically and/or cytologically-confirmed HNSCC. 4. Patient has archival or new tumor tissue for the analysis of biomarkers and confirmation of HPV status (if unknown). A recommended minimum of 5 slides for patients with known HPV status (for tumor DNA characterization) or a recommended minimum of 10 slides for patients whose HPV status is unknown (i.e. 5 slides for HPV testing and 5 slides for biomarker testing). Enrollment in the study is contingent on confirmation of the availability of an adequate amount of tumor tissue, except in rare special circumstances, which must be reviewed and approved by the sponsor. The quantity of slides to be provided is a recommendation; more slides may be requested to ensure testing can be complete. For sites in China, it is recommended a minimum of 7 unstained slides for patients with known HPV status (for tumor DNA characterization) or a minimum of 10 slides for patients whose HPV status is unknown (3 slides for HPV testing plus 7 slides, for biomarker testing. 5. Patient has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease: a. PDL1/PD1 therapy alone for metastatic or recurrent (monotherapy) disease b. PDL1/PD1 in combination with chemotherapy for metastatic or recurrent disease c. PDL1/PD1 used for metastatic disease, after or prior to receiving a platinum agent for locally advanced or metastatic disease. 6. Patient has received no more than two prior lines of systemic treatment for recurrent or metastatic HNSCC (single agent chemotherapy used as a radiosensitizer is not counted as a prior line of therapy). 7. Patient 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. 8. Patient has adequate bone marrow function and organ function as shown by the following: a. Absolute neutrophil count (ANC) >= 1.5 x 109/L. b. Hemoglobin >= 9 g/dL (which may be reached by transfusion). c. Platelets >= 100 x 109/L (which may be reached by transfusion). d. International normalized ratio (INR) <=1.5. e. Calcium (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. f. Normal potassium and magnesium levels or clinically acceptable levels as per investigators judgement and confirmation. For China only: Normal potassium and magnesium levels or <= grade 1 severity according to NCI-CTCAE version 5.0 if judged clinically not significant by the Investigator. g. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) <= 1.5 x upper limit of normal (ULN) or < 3.0 x ULN if liver metastases are present. h. Total serum bilirubin <= ULN or <= 1.5 x ULN if liver metastases are present; or total bilirubin <= 3.0 x ULN with direct bilirubin below or within normal range in patients with well documented Gilberts Syndrome. Gilberts syndrome is defined as presence of episodes of unconjugated hyperbilirubinemia with normal results from cells blood count (including normal reticulocyte count and
Exclusion criteria
Exclusion criteria: 1. Patient has received previous treatment with any protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR) inhibitors, or phosphatidylinositol 3 kinase (PI3K) pathway inhibitors. 2. Patient received treatment with a taxane as part of prior treatment for recurrent or metastatic disease. 3. Patient has symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases may participate in this study. Patient must have completed any prior local treatment for CNS metastases >= 28 days prior to the start of study treatment (including radiotherapy) and must be on a stable low dose of corticosteroid therapy. Radiosurgery must have been completed at least 14 days prior to start of study treatment. 4. Patient has received wide field radiotherapy = 2 neuropathy, colitis, pneumonitis, and uncontrolled endocrinopathies (e.g., hypothyroidism, diabetes with hemoglobin A1c > 8%) from previous treatment. 6. Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects. 7. Patient is currently receiving increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent. The following uses of corticosteroids are permitted: single doses; standard diseases), eye drops, or local injections (e.g., intra-articular), or 450 msec for males and > 470 msec for females, on the screening el
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the OS of buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with recurrent or metastatic HNSCC. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To evaluate additional efficacy parameters: progression free survival (PFS), ORR, and DoR, by the Investigator and Independent Radiological Review Committee (IRRC). 2. To evaluate efficacy parameters in subgroups of patients defined by the randomization strata. 3. To assess the effect of buparlisib in combination with paclitaxel on patients symptoms and health-related quality of life (HRQoL). 4. To assess the pharmacokinetics (PK) of buparlisib in combination with paclitaxel. | — |
Countries
Asia, Australia, Canada, Europe, Japan, United States
Contacts
Public ContactKazuhiro Kanmuri
PharmaLex Japan Inc.
Outcome results
None listed