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

Head and Neck Cancer Clinical Trial

— BURAN  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04338399
• Other study ID #: AN2025H0301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 12, 2020
• Est. completion date: June 30, 2026

Study information

• Verified date: October 2023
• Source: Adlai Nortye Biopharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 483
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• Buparlisib & Paclitaxel
Investigation drug plus paclitaxel

Locations

Country	Name	City	State
Argentina	Centro de Investigacion Pergamino SA - Clinica Pergamino S.A.	Buenos Aires
Argentina	Fundacion Cenit para la Investigacion en Neurociencias	Buenos Aires
Argentina	Instituto de Investigaciones Metabólicas (IDIM) // Instituto de Investigaciones Metabólicas S.A.	Ciudad Autonoma de Buenos Aire
Argentina	IONC SRL- Instituto Oncológico de Córdoba	Córdoba
Argentina	Fundacion CORI para la Investigacion y Prevencion del Cáncer	La Rioja
Argentina	Centro para la Atencion Integral del Paciente Oncologico - CAIPO	Tucuman
Australia	Princess Alexandra Hospital	Brisbane
Belgium	Universitair Ziekenhuis Gent UZ Gent	Ghent
Belgium	Universitair Ziekenhuis Brussel	Jette
Belgium	Clinique CHC MontLégia	Liege
Belgium	Clinique Saint-Pierre dOttignies CSPO	Ottignies
Canada	CHUM	Montreal
Canada	CancerCare Manitoba	Winnipeg
China	Beijing Tongren Hospital	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu
China	Hunan Cancer Hospital	Changsha
China	Xiangya Hospital Central South University	Changsha
China	Sichuan Cancer Hospital	Chengdu
China	Affiliated Cancer Hospital of Chongqing University	Chongqing
China	The First Affiliated Hospital of CQMU	Chongqing
China	Affiliated Cancer Hospital of Guangzhou Medical University	Guangzhou
China	Sun Yat-sen University Cancer Center	Guangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Anhui Provincial Cancer Hospital	Hefei
China	Shandong Provincial Tumor Hospital	Jinan
China	Yunnan Cancer Hospital	Kunming
China	Cancer Hospital affiliated to Guangxi Medical University	Naning
China	Shanghai Dongfang Hospital	Shanghai
China	Tianjin Cancer Hospital	Tianjin
China	Henan Cancer Hospital	Zhengzhou
China	The Fifth Affiliated Hospital of Sun Yat-sen University	Zhuhai
France	Centre hospitalier Universitaire de Bordeaux	Bordeaux
France	Centre Franois Baclesse	Caen
France	Centre Leon Berard	Lyon
France	Hopital de la Timone	Marseille
France	Institut regional du Cancer de Montpellier	Montpellier
France	LHopital prive du Confluent Nantes	Nantes
France	Clinique Hartmann	Neuilly Sur Seine
France	Hopital La Pitie Salpetriere	Paris
France	Hôpital St-Louis	Paris
France	Hopital Tenon	Paris
France	CHP Saint-Grégoire	Saint-Grégoire
France	Institut de cancerologie de Lorraine	Vandœuvre-lès-Nancy
Germany	Uniklinik RWTH Aachen	Aachen
Germany	Universitaetsklinikum Bonn	Bonn
Germany	University Hospital Essen	Essen
Germany	Franziskus Hospital	Georgsmarienhütte
Germany	HNO-Klinik des Universitats-Klinikums Giessen	Giessen
Germany	Universitatsmedizin Greifswald - KoR	Greifswald
Germany	Marienkrankenhaus Hamburg	Hamburg
Germany	Universitatsklinikum Hamburg Eppendorf	Hamburg
Germany	Hannover Medical School	Hannover
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	UNIVERSITÄTSMEDIZIN Mainz III. Klinik/Poliklinik	Mainz
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	University of Pecs Department of Oncotherapy	Pécs
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszárd
Italy	Azienda Ospedaliera Universitaria S.Orsola-Malpighi	Bologna
Italy	ASST Spedali Civili Brescia	Brescia
Italy	Istituto di Candiolo IRCCS	Candiolo
Italy	IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori	Cesena
Italy	A.O. S. Croce e Carle	Cuneo
Italy	Azienda Ospedaliero Universitaria Careggi - Firenze	Firenze
Italy	Istituto Nazionale dei Tumori	Milan
Italy	Azienda Ospedaliera San Paolo Polo Universitario	Milano
Italy	INT IRCCS Fondazione G.Pascale	Napoli
Italy	A.O.U. "Maggiore della Carita"- S.C.D.U Oncologiac	Novara
Italy	Azienda Ospedaliero Universitaria Policlinico "Paolo Giaccone" U.O.C. Oncologia Medica	Palermo
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	IRCCS Maugeri Pavia	Pavia
Italy	IRCCS Istituto Clinico Humanitas	Rozzano
Italy	AOU San Giovanni di Dio e Ruggi D'Aragona, Università degli Studi di Salerno	Salerno
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena
Italy	ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio	Sondrio
Italy	AO Card. G. Panico	Tricase
Italy	Azienda Sanitaria Universitaria Integrata di Udine	Udine
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona
Japan	Hyogo Cancer Center	Akashi-shi
Japan	National Cancer Center Hospital	Chuo Ku
Japan	Kyushu University Hospital	Fukuoka shi
Japan	Saitama Medical University International Medical Center	Hidaka
Japan	Kagawa University Hospital	Kita-gun
Japan	Kobe University Hospital	Kobe
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama
Japan	Aichi Cancer Center	Nagoya
Japan	Kindai University Hospital	Osaka Sayama-shi
Japan	Hokkaido University Hospital	Sapporo
Japan	National University Corporation Tohoku University, Tohoku University Hospital	Sendai
Japan	Showa University Hospital	Shinagawa-Ku
Japan	Shizuoka Cancer Center	Shizuoka
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul ST. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie	Gliwice
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie	Warszawa
Spain	Fundacion Oncologico de Galicia Jos Antonio Quiroga y Pieyro	A Coruña
Spain	Institut Catala d Oncologia Badalona	Badalona
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Vall dHebron Institute of Oncology (VHIO)	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital Reina Sofia	Córdoba
Spain	Hospital Duran i Reynals - Institut Catala dOncologia ICO	Hospitalet de Llobregat
Spain	Complejo Hospitalario de Jaen	Jaén
Spain	Hospital Universitario Severo Ochoa	Leganés
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	Madrid
Spain	Hospital General Universitario Gregorio Maran	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Puerta de Hierro- Majadahonda	Majadahonda
Spain	Hospital Regional de Malaga	Málaga
Spain	Hospital de Navarra	Pamplona
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario Santiago de Compostela	Santiago De Compostela
Spain	Valme Hospital Medical Oncology Department	Sevilla
Spain	Hospital Clinico Universitario Valencia - INCLIVA	Valencia
Spain	Instituto Valenciano de Oncologia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Chang Gung Memorial Hospital-KaohSiung	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi Mei Medical Center Liouying	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital-LinKou	Taoyuan
United Kingdom	Edinburgh Cancer Center	Edinburgh
United Kingdom	Beatson Oncology Centre	Glasgow
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	University College London Hospitals	London
United Kingdom	The Royal Marsden NHS Foundation Trust - Sutton	Sutton
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Montefiore Medical Center	Bronx	New York
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati Cancer Center	Cincinnati	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	West Cancer Center	Germantown	Tennessee
United States	University of Kentucky	Lexington	Kentucky
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Yale University, Yale Cancer Center	New Haven	Connecticut
United States	NYU Langone	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Hope Cancer Center, UT Health East Texas	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Adlai Nortye Biopharma Co., Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  China,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	To assess the OS of buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with recurrent or metastatic HNSCC	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.
Secondary	Progression free survival	Defined as the time from randomization date until tumor progression or death from any cause.	PFS will be assessed up to 24 months after all patients are randomized
Secondary	Overall Response Rate	Defined at the proportion of patients with a complete or partial response	ORR will be assessed for all patients 6 months after randomization is complete.
Secondary	Health Related Quality of Life (QoL): Time to Definitive deterioration of Quality of Life as assessed by EORTC C30 questionnaire	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.	Assessments will be made from randomization until treatment discontinuation
Secondary	Safety and Tolerability of Buparlisib in combination with Paclitaxel compared with Paclitaxel alone as Measured by Number of Participants Experiencing Adverse Events (AEs).	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.	From screening until 4 weeks following treatment discontinuation
Secondary	Pharmacokinetics of Buparlisib: plasma concentration-time profile of Buparlisib during 15 days of treatment	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.	Day 0 to Day 15 sparse sampling