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    Summary
    EudraCT Number:2019-000790-23
    Sponsor's Protocol Code Number:AN2025H0301
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-07-29
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2019-000790-23
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The BURAN Study of Buparlisib (AN2025) In Combination with Paclitaxel Compared to Paclitaxel Alone in patients with head and neck cancer
    A.3.2Name or abbreviated title of the trial where available
    The BURAN Study
    A.4.1Sponsor's protocol code numberAN2025H0301
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04338399
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAdlai Nortye USA Inc.,
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAdlai Nortye USA Inc.,
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAdlai Nortye USA Inc.,
    B.5.2Functional name of contact pointKevin Dreyer
    B.5.3 Address:
    B.5.3.1Street Address685 US-1,
    B.5.3.2Town/ cityNorth Brunswick Township, NJ
    B.5.3.3Post code08902
    B.5.3.4CountryUnited States
    B.5.6E-mailKevin.Dreyer@adlainortye.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBuparlisib
    D.3.2Product code AN2025 (BKM120)
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBUPARLISIB
    D.3.9.1CAS number 944396-07-0
    D.3.9.2Current sponsor codeAN2025
    D.3.9.3Other descriptive nameBUPARLISIB (BKM120)
    D.3.9.4EV Substance CodeSUB128477
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBuparlisib
    D.3.2Product code AN2025 (BKM120)
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBUPARLISIB
    D.3.9.1CAS number 944396-07-0
    D.3.9.2Current sponsor codeAN2025
    D.3.9.3Other descriptive nameBUPARLISIB (BKM120)
    D.3.9.4EV Substance CodeSUB128477
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Paclitaxel
    D.2.1.1.2Name of the Marketing Authorisation holderEbewe Pharma Ges.m.b.H. Nfg. KG
    D.2.1.2Country which granted the Marketing AuthorisationBulgaria
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePaclitaxel
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPaclitaxel
    D.3.9.1CAS number 33069-62-4
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number30 to 300
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBuparlisib
    D.3.2Product code AN2025 (BKM120)
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBuparlisib
    D.3.9.1CAS number 944396-07-0
    D.3.9.2Current sponsor codeAN2025
    D.3.9.3Other descriptive nameBUPARLISIB (BKM120)
    D.3.9.4EV Substance CodeSUB128477
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBuparlisib
    D.3.2Product code AN2025 (BKM120)
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBuparlisib
    D.3.9.1CAS number 944396-07-0
    D.3.9.2Current sponsor codeAN2025
    D.3.9.3Other descriptive nameBUPARLISIB (BKM120)
    D.3.9.4EV Substance CodeSUB128477
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Head and Neck Squamous Cell Carcinoma (HNSCC)
    E.1.1.1Medical condition in easily understood language
    Head and Neck Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    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 the pharmacokinetics (PK) of buparlisib in combination with paclitaxel.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must meet the following criteria to be eligible for enrollment into the study:
    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.
    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.
    d. For France patients only a specific inclusion criteria was added - please refer to PA5.01.
    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 investigator’s judgement and confirmation.
    For France patients only a specific inclusion criteria was added - please refer to PA5.01.
    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 Gilbert’s Syndrome. Gilbert’s syndrome is defined as presence of episodes of unconjugated hyperbilirubinemia with normal results from cells blood count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis.
    i. Serum creatinine ≤ 1.5 x ULN or calculated and directly measured creatinine clearance (CrCL) > 30 mL/min.
    j. HbA1c≤8%.
    9. Patient has Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
    10. 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. Female partners of male participants are to use highly effective contraception while the male participants are receiving treatment and for at least 90 days after their partner’s last buparlisib dose, or until at least 6 months after their partner’s last paclitaxel dose, whichever is longer. 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 90 days after the final dose of buparlisib or as specified in the local prescription guidelines for paclitaxel (e.g., for six months after final dose of paclitaxel according to the product insert/Summary of Product Characteristics [SmPC] from France & UK, whichever is longer.
    E.4Principal 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 ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study treatment or who have adverse events which have not recovered to grade 1 or better from previous chemotherapy treatment (except alopecia, autoimmune endocrine events must be stable and controlled).5.Patient has grade ≥ 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 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 < 10 mg prednisolone or equivalent.9.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.10.Patient has a known hypersensitivity and/or contraindication to paclitaxel, standard premedication for paclitaxel, or other products containing Cremophor®.11.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).12.Patient has a known history of HIV infection (testing not mandatory).13.Patient has any of the following cardiac abnormalities: a.Symptomatic congestive heart failure within 12 months of the screening period. b.History of documented congestive heart failure (New York Heart Association functional classification III-IV) or documented cardiomyopathy and left ventricular ejection fraction (LVEF) <50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO). c.Myocardial infarction ≤six months prior to enrollment. d.Unstable angina pectoris. e.Serious uncontrolled cardiac arrhythmia.f.Symptomatic pericarditis. g.QT interval corrected according to the formula of Fridericia (QTcF) > 450 msec for males and > 470 msec for females, on the screening electrocardiogram (ECG).14.Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug. 15.Patient has a medically documented history of mental disorders with poor control, including 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. For patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous six weeks prior to start of study drug. 20. Patient has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed. Non-live COVID vaccinations/boosters may be administered during a patient’s participation of the trial, however it is recommended this not occur within 30 days of study start (C1D1) or during Cycle 1 for those patients randomized to the buparlisib arm. Patients are not to be excluded if administration of the non-live COVID vaccinations or boosters occurs within 30 days of a patient’s C1D1 or during cycle1. For exclusion criteria 8, 16 to 19 please refer to the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is OS.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary statistical efficacy endpoint of the study is OS, defined as the time from randomization to death due to any cause. Patients who are not reported as having died at the time of analysis will be censored at the date when they were last known to be alive.
    E.5.2Secondary end point(s)
    The secondary endpoints of this study are as follows:
    Efficacy:
    • PFS as assessed by IRRC and by investigator
    • Overall response rate (ORR) as assessed by IRRC and by investigator
    • Duration of response (DoR) as assessed by IRRC and by investigator
    • OS, PFS, ORR and DoR in subgroups of patients defined by the randomization strata (HPV status)
    • 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

    Safety:
    • AEs
    • Clinical laboratory tests
    • PHQ-9
    • GAD-7
    E.5.2.1Timepoint(s) of evaluation of this end point
    N/A
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA75
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United Kingdom
    United States
    Belgium
    France
    Germany
    Hungary
    Italy
    Poland
    Spain
    E.8.7Trial 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
    Last visit of last subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 277
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 206
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 249
    F.4.2.2In the whole clinical trial 483
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients will revert to their normal standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-09-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-30
    P. End of Trial
    P.End of Trial StatusOngoing
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