Study of Efficacy and Safety of Buparlisib (BKM120) Plus Paclitaxel Versus Placebo Plus Paclitaxel in Recurrent or Metastatic Head and Neck Cancer Previously Pre-treated With a Platinum Therapy

NCT01852292 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CBKM120H22012013-000744-26
• Study Type: interventional
• Target: 157
• Locations: 18 countries
• Sites: 58

Brief Summary

Phase II Study of efficacy and safety of buparlisib (BKM120) plus paclitaxel versus placebo plus paclitaxel in recurrent or metastatic Head and Neck cancer previously pre-treated with a platinum therapy.The primary endpoint was PFS and the key secondary endpoint was Overall Survival.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

platinum pre-treated recurrent or metastatic; Head and neck squamous cell carcinoma; recurrent; metastatic; BKM120

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Per Investigator Assessment

  PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression per RECIST v. 1.1 or death due to any cause. If a patient has not progressed or died at the analysis cut-off date or when the patient receives further anti-neoplastic therapy, PFS was censored on the date of the last adequate tumor assessment before the earlier of the cut-off date or start of the further anti-neoplastic therapy date.

  4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Secondary Outcomes (11)

• Overall Survival (OS)

  4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

• Overall Response Rate (ORR) as Per Local Radiological Assessment

  4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

• Time to Response (TTR) as Per Local Radiological Assessment

  4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

• Disease Control Rate (DCR) as Per Local Radiological Assessment

  4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

• Duration of Response (DoR) as Per Local Investigator

  4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Study Arms (2)

Buparlisib + weekly Paclitaxel

EXPERIMENTAL

Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m\^2 weekly.

Drug: Buparlisib; Drug: Paclitaxel

Buparlisib matching placebo + Paclitaxel

PLACEBO COMPARATOR

Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m\^2 weekly.

Drug: Buparlisib matching Placebo; Drug: Paclitaxel

Interventions

Buparlisib DRUG

Buparlisib comes in gelatin capsules and is taken orally at a dose of 100 mg/day.

Also known as: BKM120

Buparlisib + weekly Paclitaxel

Buparlisib matching Placebo DRUG

Buparlisib matching placebo comes in gelatin capsules and is taken orally at a dose of 100 mg/day.

Buparlisib matching placebo + Paclitaxel

Paclitaxel DRUG

Paclitaxel is an intravenous infusion that is given once every week in 80 mg/m\^2.

Buparlisib + weekly Paclitaxel; Buparlisib matching placebo + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has histologically/cytologically-confirmed HNSCC.
• Patient has archival or fresh tumor tissue for the analysis of PI3K-related biomarkers. One tumor block (preferred) or a minimum of 12 unstained slides to be provided. Enrollment in the study is contingent on confirmation of an adequate amount of tumor tissue.
• Patients with recurrent or metastatic disease resistant to platinum-based chemotherapy (defined as progression while on platinum-based chemotherapy given in the recurrent/metastatic setting). Pretreatment with cetuximab is allowed
• Measurable disease as determined by per RECIST criteria v1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a 4 week period since radiotherapy completion is required
• Adequate bone marrow function and organ function
• ECOG Performance Status ≤ 1

You may not qualify if:

• Patient has received previous treatment with any AKT, mTOR inhibitors or PI3K pathway inhibitors;
• Patient treated with more than one prior chemotherapy regimen for recurrent/metastatic disease
• Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have stable low dose of corticosteroid therapy;
• Patient has not recovered to ≤ grade 1 (except alopecia) from related side effects of any prior antineoplastic therapy
• Patient has any of the following cardiac abnormalities:symptomatic congestive heart failure, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO); myocardial infarction ≤ 6 months prior to enrolment, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, QTcF \> 480 msec on the screening ECG (using the QTcF formula);

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (58)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Dana Farber Cancer Institute IRB

Boston, Massachusetts, 02215, United States

Location

Washington U School of Medicine Center for Clinical Studies SC - BKM120H2201

St Louis, Missouri, 63110, United States

Location

The Mount Sinai Hospital Dept of Oncology

New York, New York, 10029, United States

Location

University of N.C. at Chapel Hill Lineberger Comp. Cancer Ctr.

Chapel Hill, North Carolina, 27599-7600, United States

Location

University Hospitals Case Medical Center Univ. Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

UPMC Cancer Centers BKM120H2201

Pittsburgh, Pennsylvania, 15232, United States

Location

Novartis Investigative Site

St Leonards, New South Wales, 2065, Australia

Location

Novartis Investigative Site

Hamilton, Ontario, L8V 5C2, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2L 4M1, Canada

Location

Novartis Investigative Site

Saint-Herblain, 44805, France

Location

Novartis Investigative Site

Berlin, 12203, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Budapest, 1082, Hungary

Location

Novartis Investigative Site

Budapest, H-1115, Hungary

Location

Novartis Investigative Site

Budapest, H-1122, Hungary

Location

Novartis Investigative Site

Nyíregyháza, 4400, Hungary

Location

Novartis Investigative Site

Nashik, Maharashtra, 422 004, India

Location

Novartis Investigative Site

Dehli, New Delhi, 110005, India

Location

Novartis Investigative Site

Jaipur, Rajasthan, 302017, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700160, India

Location

Novartis Investigative Site

Kerala, 695 011, India

Location

Novartis Investigative Site

Mumbai, 400 012, India

Location

Novartis Investigative Site

Dublin, Ireland

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Milan, MI, 20142, Italy

Location

Novartis Investigative Site

Palermo, PA, 90127, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Salerno, SA, 84131, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Venezia, VE, 30174, Italy

Location

Novartis Investigative Site

Kashiwa, Chiba, 277-8577, Japan

Location

Novartis Investigative Site

Koto-ku, Tokyo, 135 8550, Japan

Location

Novartis Investigative Site

Minato-ku, Tokyo, 105-8471, Japan

Location

Novartis Investigative Site

Warsaw, 02-781, Poland

Location

Novartis Investigative Site

Leningrad Region, Russia, 188663, Russia

Location

Novartis Investigative Site

Nizhny Novgorod, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197758, Russia

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, Seocho-gu, 06591, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

Novartis Investigative Site

Tainan, Taiwan ROC, 70421, Taiwan

Location

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

Location

Novartis Investigative Site

Taichung, 407, Taiwan

Location

Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Novartis Investigative Site

London, NW1 2PJ, United Kingdom

Location

Novartis Investigative Site

London, SE1 9RT, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 9BX, United Kingdom

Location

Related Publications (2)

• Desilets A, Lucas J, Licitra LF, Lu S, Tse A, Tang T, Dreyer K, He N, Birgerson LE, Faivre S, Soulieres D. Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study. Target Oncol. 2025 Mar;20(2):299-310. doi: 10.1007/s11523-024-01126-0. Epub 2025 Jan 14.

  PMID: 39808408 DERIVED

• Soulieres D, Faivre S, Mesia R, Remenar E, Li SH, Karpenko A, Dechaphunkul A, Ochsenreither S, Kiss LA, Lin JC, Nagarkar R, Tamas L, Kim SB, Erfan J, Alyasova A, Kasper S, Barone C, Turri S, Chakravartty A, Chol M, Aimone P, Hirawat S, Licitra L. Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Oncol. 2017 Mar;18(3):323-335. doi: 10.1016/S1470-2045(17)30064-5. Epub 2017 Jan 26.

  PMID: 28131786 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis; Recurrence

Interventions

NVP-BKM120; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 13, 2013
• Study Start: October 1, 2013
• Primary Completion: March 30, 2017
• Study Completion: March 30, 2017
• Last Updated: July 24, 2018
• Results First Posted: June 26, 2018

Record last verified: 2018-06

Locations

ES (3); JP (3); TH (3); KR (2); US (7); HU (4); PL (1); DE (3); TW (3); AU (1); CA (2); IT (9); FR (1); IE (1); RU (3); IN (6); CH (2); GB (4)