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

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ClinicalTrials.gov Identifier: NCT04338399
Recruitment Status : Recruiting
First Posted : April 8, 2020
Last Update Posted : January 7, 2021
Sponsor:
Information provided by (Responsible Party):
Adlai Nortye Biopharma Co., Ltd.

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 platinum-based therapy with or without prior anti PD 1/anti PD L1 therapy.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Drug: Buparlisib & Paclitaxel Phase 3

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 who have failed cisplatin based treatment or cisplatin based treatment and anti-PD1 based treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 483 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 12, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
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.

Drug: Buparlisib & Paclitaxel
Investigation drug plus paclitaxel
Other Name: AN2025

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.
Drug: Buparlisib & Paclitaxel
Investigation drug plus paclitaxel
Other Name: AN2025




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.


  5. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. One 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 (optional).
  5. Patient has either:

    1. refractory disease defined as progression or recurrence within six months after the last dose of platinum based chemotherapy in combination with radiation therapy for locally advanced disease given with a curative intent or
    2. disease progression after platinum based chemotherapy for recurrent or metastatic disease or
    3. recurrent or metastatic disease after platinum based chemotherapy and anti PD 1/anti PD L1 treatment (defined as progression after one month from the last dose of anti PD 1/anti PD L1 therapy). Pretreatment with cetuximab as part of chemoradiation, first-line therapy or maintenance is allowed.
  6. Patient has received no more than two prior lines of treatment for HNSCC.
  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. 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.
    7. 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.
    8. Serum creatinine ≤1.5 x ULN or calculated or directly measured creatinine clearance (CrCL) >30 mL/min.
    9. 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 only received anti-PD 1/anti PD L1 monotherapy for HNSCC.
  4. 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.
  5. Patient has received wide field radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study treatment or who have not recovered to grade 1 or better from related side effects of such therapy (except alopecia).
  6. Patient has grade ≥2 neuropathy, colitis, pneumonitis, elevated HbA1C, and uncontrolled endocrinopathies (e.g., hypothyroidism) from previous treatment.
  7. Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.
  8. 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 being treated at start of study treatment with any of the following drugs:

    1. Drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4) including herbal medications.
    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.
  10. 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.
  11. Patient has a known hypersensitivity and/or contraindication to paclitaxel, standard premedication for paclitaxel, or other products containing Cremophor®.
  12. 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).
  13. Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory).
  14. Patient has any of the following cardiac abnormalities:

    1. Symptomatic congestive heart failure.
    2. History of documented congestive heart failure (New York Heart Association functional classification III-IV) or documented cardiomyopathy.
    3. Left ventricular ejection fraction (LVEF) <50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
    4. Myocardial infarction ≤six months prior to enrollment.
    5. Unstable angina pectoris.
    6. Serious uncontrolled cardiac arrhythmia.
    7. Symptomatic pericarditis.
    8. QT interval corrected according to the formula of Fridericia (QTcF) >450 msec for males and >470 msec for females, on the screening electrocardiogram (ECG).
    9. 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.
  15. 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).
  16. 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.
  17. 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.
  18. Patient has a history of non-compliance to any medical regimen or inability to grant consent.
  19. Patient is concurrently using other approved or investigational cancer agent.
  20. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04338399


Contacts
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Contact: Doug Project Manager +1 919 926 5650 douglas.brott@syneoshealth.com

Locations
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United States, New Jersey
Hope Cancer Center Recruiting
North Brunswick, New Jersey, United States, 08902
Contact: Jenny Collins, RN         
Sponsors and Collaborators
Adlai Nortye Biopharma Co., Ltd.
Investigators
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Study Director: Senior Director, Global Operations Adlai Nortye
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Responsible Party: Adlai Nortye Biopharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT04338399    
Other Study ID Numbers: AN2025H0301
First Posted: April 8, 2020    Key Record Dates
Last Update Posted: January 7, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Adlai Nortye Biopharma Co., Ltd.:
Buparlisib
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action