The BURAN Study of Buparlisib (AN2025) In Combination with Paclitaxel Compared to Paclitaxel Alone, in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Primary Objectives The primary objective of this study is to assess the OS of buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with recurrent or metastatic HNSCC. Secondary Objectives * To evaluate additional efficacy parameters including progression free survival (PFS), overall response rate (ORR), and duration of response (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 healthrelated 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.
Chemotherapy (NOS); Therapy (NOS)
BKM120 (Buparlisib); Buparlisib (); Taxol (paclitaxel); paclitaxel ()
- Able to provide informed consent
- Patient has histologically and/or cytologically-confirmed HNSCC
- Patient has archival or new tumor tissue for the analysis of biomarkers and confirmation of HPV status (if unknown). One tumor block (preferred) or a recommended minimum of 5 unstained 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 (5 slides for HPV testing plus 5 slides needed 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
- Patient has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease
- Patient 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)
- 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.
- Patient has adequate bone marrow function and organ function
- 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
- 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.
- Patient received treatment with a taxane as part of prior treatment for metastatic disease.
- 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.
- Patient has received wide field radiotherapy > Patient has grade > 2 neuropathy, colitis, pneumonitis, , and uncontrolled endocrinopathies (e.g., hypothyroidism, diabetes with hemoglobin A1c > 8%) from previous treatment
- Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.
- 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 premedication for paclitaxel, topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops, or local injections (e.g., intra-articular), or > Patient is being treated at start of study treatment with any of the following drugs: Drugs known to be strong or moderate inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4) including herbal medications; Drugs with a known risk of inducing Torsades de Pointes
- Patient is currently receiving warfarin or other coumarin-derived anti-coagulant, for treatment, prophylaxis, or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), fondaparinux or new oral anticoagulants (NOACs) is allowed.
- Patient has a known hypersensitivity and/or contraindication to paclitaxel, standard premedication for paclitaxel, or other products containing Cremophor
- Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the Investigator's judgment, contraindicate patient participation in the clinical study (e.g., active or uncontrolled severe infection, chronic active hepatitis, immunocompromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc).
- Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory).
- Patient has cardiac abnormalities defined in protocol
- Patient has impairment of gastrointestinal (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 (e.g., risk of doing harm to self or others), or active severe personality disorders (defined according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition [DSM-V]) are not eligible.
- Additional criteria will apply
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