NCT04338399

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
487

participants targeted

Target at P75+ for phase_3 head-and-neck-cancer

Timeline
Completed

Started Dec 2020

Geographic Reach
17 countries

162 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 18, 2020

Completed
21 days until next milestone

First Posted

Study publicly available on registry

April 8, 2020

Completed
8 months until next milestone

Study Start

First participant enrolled

December 12, 2020

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 2, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 2, 2025

Completed
Last Updated

November 17, 2025

Status Verified

November 1, 2025

Enrollment Period

4.9 years

First QC Date

March 18, 2020

Last Update Submit

November 14, 2025

Conditions

Keywords

BuparlisibPD1PDL1

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (5)

  • Progression free survival

    PFS will be assessed up to 24 months after all patients are randomized

  • Overall Response Rate

    ORR will be assessed for all patients 6 months after randomization is complete.

  • Health Related Quality of Life (QoL): Time to Definitive deterioration of Quality of Life as assessed by EORTC C30 questionnaire

    Assessments will be made from randomization until treatment discontinuation

  • Safety and Tolerability of Buparlisib in combination with Paclitaxel compared with Paclitaxel alone as Measured by Number of Participants Experiencing Adverse Events (AEs).

    From screening until 4 weeks following treatment discontinuation

  • Pharmacokinetics of Buparlisib: plasma concentration-time profile of Buparlisib during 15 days of treatment

    Day 0 to Day 15 sparse sampling

Study Arms (2)

Buparlisib & Weekly Paclitaxel

EXPERIMENTAL

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.

Weekly Paclitaxel

ACTIVE COMPARATOR

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

Interventions

Investigation drug plus paclitaxel

Also known as: AN2025
Weekly Paclitaxel

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged ≥18 years old.
  • Able to provide informed consent obtained before any trial related activities and according to local guidelines.
  • 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:
  • PDLl/PD1 therapy alone for metastatic (monotherapy) disease
  • PDL1/PD1 in combination with chemotherapy for metastatic and recurrent disease
  • PDL1/PD1 used for metastatic disease, after or prior to receiving a platinum agent for locally advanced 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 as shown by the following:
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L.
  • Hemoglobin ≥9 g/dL (which may be reached by transfusion).
  • Platelets ≥100 x 109/L (which may be reached by transfusion).
  • International normalized ratio (INR) ≤1.5.
  • +10 more criteria

You may not qualify if:

  • Patients meeting any of the following criteria will not be eligible for participation in the study:
  • 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 ≤ 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).
  • 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 \< 10 mg prednisolone or equivalent.
  • 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 (see Table 16).
  • 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.
  • 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).
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (162)

City of Hope

Duarte, California, 91010, United States

Location

Yale University, Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63130, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45219, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Hope Cancer Center, UT Health East Texas

Tyler, Texas, 75701, United States

Location

Fundacion Cenit para la Investigacion en Neurociencias

Buenos Aires, 1125, Argentina

Location

Centro de Investigacion Pergamino SA - Clinica Pergamino S.A.

Buenos Aires, B2700CPM, Argentina

Location

Instituto de Investigaciones Metabólicas (IDIM) // Instituto de Investigaciones Metabólicas S.A.

Ciudad Autonoma de Buenos Aire, C1012AAR, Argentina

Location

IONC SRL- Instituto Oncológico de Córdoba

Córdoba, X5002HWE, Argentina

Location

Fundacion CORI para la Investigacion y Prevencion del Cáncer

La Rioja, F5300COE, Argentina

Location

Centro para la Atencion Integral del Paciente Oncologico - CAIPO

San Miguel de Tucumán, T4000GTB, Argentina

Location

Princess Alexandra Hospital

Brisbane, 4102, Australia

Location

Universitair Ziekenhuis Gent UZ Gent

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Brussel

Jette, 1090, Belgium

Location

Clinique CHC MontLégia

Liège, 4000, Belgium

Location

Clinique Saint-Pierre dOttignies CSPO

Ottignies, 1340, Belgium

Location

CHUM

Montreal, H2X 0C2, Canada

Location

CancerCare Manitoba

Winnipeg, R3E 0V9, Canada

Location

Beijing Tongren Hospital

Beijing, 100176, China

Location

The First Affiliated Hospital of Bengbu Medical College

Bengbu, 233004, China

Location

Hunan Cancer Hospital

Changsha, 410000, China

Location

Xiangya Hospital Central South University

Changsha, 410000, China

Location

Sichuan Cancer Hospital

Chengdu, 610042, China

Location

Affiliated Cancer Hospital of Chongqing University

Chongqing, 400000, China

Location

The First Affiliated Hospital of CQMU

Chongqing, 400042, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, 510000, China

Location

Affiliated Cancer Hospital of Guangzhou Medical University

Guangzhou, 510095, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Anhui Provincial Cancer Hospital

Hefei, 230031, China

Location

Shandong Provincial Tumor Hospital

Jinan, 250000, China

Location

Yunnan Cancer Hospital

Kunming, 650000, China

Location

Cancer Hospital affiliated to Guangxi Medical University

Naning, 530021, China

Location

Shanghai Dongfang Hospital

Shanghai, 310115, China

Location

Tianjin Cancer Hospital

Tianjin, 300202, China

Location

Henan Cancer Hospital

Zhengzhou, 450000, China

Location

The Fifth Affiliated Hospital of Sun Yat-sen University

Zhuhai, 519000, China

Location

Centre hospitalier Universitaire de Bordeaux

Bordeaux, 33075, France

Location

Centre Franois Baclesse

Caen, 14000, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Hopital de la Timone

Marseille, 13005, France

Location

Institut regional du Cancer de Montpellier

Montpellier, 34298, France

Location

LHopital prive du Confluent Nantes

Nantes, 44277, France

Location

Clinique Hartmann

Neuilly-sur-Seine, 92200, France

Location

Hôpital St-Louis

Paris, 75010, France

Location

Hopital La Pitie Salpetriere

Paris, 75013, France

Location

Hopital Tenon

Paris, 75970, France

Location

CHP Saint-Grégoire

Saint-Grégoire, 35760, France

Location

Institut de cancerologie de Lorraine

Vandœuvre-lès-Nancy, 54500, France

Location

Uniklinik RWTH Aachen

Aachen, 52074, Germany

Location

Universitaetsklinikum Bonn

Bonn, 53127, Germany

Location

University Hospital Essen

Essen, 45147, Germany

Location

Franziskus Hospital

Georgsmarienhütte, 49124, Germany

Location

HNO-Klinik des Universitats-Klinikums Giessen

Giessen, 35392, Germany

Location

Universitatsmedizin Greifswald - KoR

Greifswald, 17489, Germany

Location

Universitatsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Marienkrankenhaus Hamburg

Hamburg, 22045, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

UNIVERSITÄTSMEDIZIN Mainz III. Klinik/Poliklinik

Mainz, 55131, Germany

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

University of Pecs Department of Oncotherapy

Pécs, 7624, Hungary

Location

Tolna Megyei Balassa Janos Korhaz

Szekszárd, 7100, Hungary

Location

Azienda Ospedaliera Universitaria S.Orsola-Malpighi

Bologna, 40138, Italy

Location

ASST Spedali Civili Brescia

Brescia, 25123, Italy

Location

Istituto di Candiolo IRCCS

Candiolo, 10060, Italy

Location

IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori

Cesena, Italy

Location

A.O. S. Croce e Carle

Cuneo, 12100, Italy

Location

Azienda Ospedaliero Universitaria Careggi - Firenze

Florence, 50134, Italy

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Ospedaliera San Paolo Polo Universitario

Milan, 20142, Italy

Location

INT IRCCS Fondazione G.Pascale

Napoli, 80131, Italy

Location

A.O.U. "Maggiore della Carita"- S.C.D.U Oncologiac

Novara, 28100, Italy

Location

Azienda Ospedaliero Universitaria Policlinico "Paolo Giaccone" U.O.C. Oncologia Medica

Palermo, 90127, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, 43126, Italy

Location

IRCCS Maugeri Pavia

Pavia, 27100, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

AOU San Giovanni di Dio e Ruggi D'Aragona, Università degli Studi di Salerno

Salerno, 84131, Italy

Location

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, 53100, Italy

Location

ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio

Sondrio, 23100, Italy

Location

AO Card. G. Panico

Tricase, 73039, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine

Udine, 33100, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126, Italy

Location

Hyogo Cancer Center

Akashi-shi, 673-8558, Japan

Location

National Cancer Center Hospital

Chūōku, 104-0045, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Saitama Medical University International Medical Center

Hidaka, 350-1298, Japan

Location

Kagawa University Hospital

Kita-gun, 761-0793, Japan

Location

Kobe University Hospital

Kobe, 650-0017, Japan

Location

The Cancer Institute Hospital of JFCR

Kōtoku, 135-8550, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, 791-0280, Japan

Location

Aichi Cancer Center

Nagoya, 464-8681, Japan

Location

Kindai University Hospital

Osaka Sayama-shi, 589-8511, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

National University Corporation Tohoku University, Tohoku University Hospital

Sendai, 980-8574, Japan

Location

Showa University Hospital

Shinagawa-Ku, 142-8666, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie

Gliwice, 44-102, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie

Warsaw, 02-781, Poland

Location

Kosin University Gospel Hospital

Busan, 49267, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 2841, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

The Catholic University of Korea Seoul ST. Mary's Hospital

Seoul, 6591, South Korea

Location

Korea University Guro Hospital

Seoul, 8308, South Korea

Location

Ajou University Hospital

Suwon, 16499, South Korea

Location

Fundacion Oncologico de Galicia Jos Antonio Quiroga y Pieyro

A Coruña, 15009, Spain

Location

Institut Catala d Oncologia Badalona

Badalona, 08916, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Vall dHebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital Reina Sofia

Córdoba, 14004, Spain

Location

Complejo Hospitalario de Jaen

Jaén, 23007, Spain

Location

Hospital Duran i Reynals - Institut Catala dOncologia ICO

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario Severo Ochoa

Leganés, 28911, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Clinico Universitario Virgen de la Arrixaca

Madrid, 30120, Spain

Location

Hospital General Universitario Gregorio Maran

Madrid, Spain

Location

Hospital Puerta de Hierro- Majadahonda

Majadahonda, 28220, Spain

Location

Hospital Regional de Malaga

Málaga, 29010, Spain

Location

Hospital de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Valme Hospital Medical Oncology Department

Seville, 41014, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario Valencia - INCLIVA

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Chang Gung Memorial Hospital-KaohSiung

Kaohsiung City, 833, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704017, Taiwan

Location

Chi Mei Medical Center Liouying

Tainan, 73657, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital-LinKou

Taoyuan District, 33342, Taiwan

Location

Edinburgh Cancer Center

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson Oncology Centre

Glasgow, G12 0YN, United Kingdom

Location

University College London Hospitals

London, NW1 2BU, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Royal Marsden NHS Foundation Trust - Sutton

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

NVP-BKM120Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasms

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Officials

  • Senior Director, Global Operations

    Adlai Nortye USA Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 18, 2020

First Posted

April 8, 2020

Study Start

December 12, 2020

Primary Completion

November 2, 2025

Study Completion

November 2, 2025

Last Updated

November 17, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will not share

Locations