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The BURAN Study of Buparlisib in Patients With Recurrent or Metastatic HNSCC (BURAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04338399
Recruitment Status : Recruiting
First Posted : April 8, 2020
Last Update Posted : January 20, 2022
Information provided by (Responsible Party):
Adlai Nortye Biopharma Co., Ltd.

Tracking Information
First Submitted Date  ICMJE March 18, 2020
First Posted Date  ICMJE April 8, 2020
Last Update Posted Date January 20, 2022
Actual Study Start Date  ICMJE December 12, 2020
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2020)
Overall Survival (OS) [ Time Frame: Overall survival will be measured from time of randomization until death from any cause. The analysis will occur when all patients have been randomized and followed for 12 months. ]
To assess the OS of buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with recurrent or metastatic HNSCC
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2020)
  • Progression free survival [ Time Frame: PFS will be assessed up to 24 months after all patients are randomized ]
    Defined as the time from randomization date until tumor progression or death from any cause.
  • Overall Response Rate [ Time Frame: ORR will be assessed for all patients 6 months after randomization is complete. ]
    Defined at the proportion of patients with a complete or partial response
  • Health Related Quality of Life (QoL): Time to Definitive deterioration of Quality of Life as assessed by EORTC C30 questionnaire [ Time Frame: Assessments will be made from randomization until treatment discontinuation ]
    A summary of EORTC-QLQ-C30 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment when definitive deterioration is seen. Definitive deterioration is defined as a decrease in the sub scale score by at least 10% compared with baseline.
  • Safety and Tolerability of Buparlisib in combination with Paclitaxel compared with Paclitaxel alone as Measured by Number of Participants Experiencing Adverse Events (AEs). [ Time Frame: From screening until 4 weeks following treatment discontinuation ]
    Treatment Emergent Adverse Events AEs will be assessed according to the NCI-CTCAE version 5.0 for severity and will be recorded and classified on the basis of MedDRA terminology. Anxiety score change from baseline taken at time of screening (General Anxiety Disorder 7 item scale) until end of treatment. Depression score change from baseline taken at time of screening (Patient Health Questionnaire 9) until end of treatment.
  • Pharmacokinetics of Buparlisib: plasma concentration-time profile of Buparlisib during 15 days of treatment [ Time Frame: Day 0 to Day 15 sparse sampling ]
    For Sparse PK sampling, blood samples will be collected on Treatment Cycle 1, Days 1, 8, and 15 at pre-dose, 1 (± 0.25), 2 ± (0.25) and 6 ± (0.5) hours post-dose. PK sampling will be collected only for those patients randomized to the buparlisib in combination with paclitaxel arm and pharmacokinetic profile of Buparlisib combined with paclitaxel in the study population will be compared with a simulated population PK model.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE The BURAN Study of Buparlisib in Patients With Recurrent or Metastatic HNSCC
Official Title  ICMJE 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
Brief Summary The BURAN study is a randomized, open-label phase III study to assess the treatment effect of once-daily buparlisib in combination with weekly paclitaxel compared to weekly paclitaxel alone in patients with refractory, recurrent, or metastatic head and neck squamous cell carcinoma (HNSCC) that have progressed after prior anti PD 1/anti PD L1 monotherapy; prior anti PD 1/anti PD L1 therapy in combination with platinum-based therapy; or after sequential treatment of anti PD 1/anti PD L1 therapy, either prior to or post, platinum-based therapy.
Detailed Description This study is to assess the impact on overall survival of the combination of Buparlisib and paclitaxel compared to paclitaxel alone in patients with prior anti PD 1/anti PD L1 monotherapy; prior anti PD 1/anti PD L1 therapy in combination with platinum-based therapy; or after sequential treatment of anti PD 1/anti PD L1 therapy, either prior to or post, platinum-based therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Cancer
Intervention  ICMJE Drug: Buparlisib & Paclitaxel
Investigation drug plus paclitaxel
Other Name: AN2025
Study Arms  ICMJE
  • Experimental: Buparlisib & Weekly Paclitaxel

    Drug: Patients will receive 100 mg (2 x 50 mg) buparlisib hard gel capsule administered orally, once daily starting on Day 1 of Treatment Cycle 1, Drug: Paclitaxel (80 mg/m2) administered intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle.

    Treatment will continue until disease progression, unacceptable toxicity, death or discontinuation for any other reason.

    Intervention: Drug: Buparlisib & Paclitaxel
  • Active Comparator: Weekly Paclitaxel
    Patients will receive weekly paclitaxel (80 mg/m2) administered intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle. Treatment will continue until disease progression, unacceptable toxicity, death or discontinuation for any other reason.
    Intervention: Drug: Buparlisib & Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 6, 2020)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Aged ≥18 years old.
  2. Able to provide informed consent obtained before any trial 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). 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.
  5. Patient has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease:

    1. PDLl/PD1 therapy alone for metastatic (monotherapy) disease
    2. PDL1/PD1 in combination with chemotherapy for metastatic and recurrent disease
    3. PDL1/PD1 used for metastatic disease, after or prior to receiving a platinum agent for locally advanced or metastatic disease.
  6. 6. 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).
  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:

    1. Absolute neutrophil count (ANC) ≥1.5 x 109/L.
    2. Hemoglobin ≥9 g/dL (which may be reached by transfusion).
    3. Platelets ≥100 x 109/L (which may be reached by transfusion).
    4. International normalized ratio (INR) ≤1.5.
    5. 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.

    6. Normal potassium and magnesium levels.
    7. 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.
    8. 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.
    9. Serum creatinine ≤ 1.5 x ULN or calculated and directly measured creatinine clearance (CrCL) > 30 mL/min.
    10. Haemoglobin A1c (glycosylated hemoglobin; HbA1c) ≤8%.
  9. Patient has Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
  10. 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.
  11. Patients must apply highly effective contraception during and throughout the study, as well after the final dose of study treatment

Exclusion Criteria:

Patients meeting any of the following criteria will not be eligible for participation in the study:

  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 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.
  8. Patient is being treated at start of study treatment with any of the following drugs:

    1. Drugs known to be strong or moderate inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4) including herbal medications (see Table 16).
    2. Drugs with a known risk of inducing Torsades de Pointes. Note: The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to starting study treatment is allowed.
  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 human immunodeficiency virus (HIV) infection (testing not mandatory).
  13. Patient has any of the following cardiac abnormalities:

    1. Symptomatic congestive heart failure within 12 months of the screening period.
    2. 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).
    3. Myocardial infarction ≤six months prior to enrollment.
    4. Unstable angina pectoris.
    5. Serious uncontrolled cardiac arrhythmia.
    6. Symptomatic pericarditis.
    7. QT interval corrected according to the formula of Fridericia (QTcF) > 450 msec for males and > 470 msec for females, on the screening electrocardiogram (ECG).
    8. 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.
  14. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  15. 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. Note: 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 treatment.
  16. Patient 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 or any other cancer from which the patient has been disease free for ≥ 3years.
  17. Patient has a history of non-compliance to any medical regimen or inability to grant consent.
  18. Patient is concurrently using or has used another approved or investigational cancer agent within 4 weeks of randomization.
  19. Patient is pregnant or nursing (lactating). Patients with elevated human chorionic gonadotrophin (hCG) at baseline that is judged to be related to the tumor are eligible if hCG levels do not show the expected doubling when repeated five to seven days later, or pregnancy has been ruled out by vaginal ultrasound.
  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 or boosters should not occur within 30 days of study start.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Namita Rao +91 988 608 1597
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04338399
Other Study ID Numbers  ICMJE AN2025H0301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Adlai Nortye Biopharma Co., Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Adlai Nortye Biopharma Co., Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Senior Director, Global Operations Adlai Nortye USA Inc.
PRS Account Adlai Nortye Biopharma Co., Ltd.
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP