Clinical trial NCT01166542: Efficacy Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Platinum-Refractory Head and Neck Cancers
Official title: Randomized, Double-blind, Multicenter Two-Stage Adaptive Phase 3 Study of Intravenous Administration of REOLYSIN (Reovirus Type 3 Dearing) in Combination With Paclitaxel and Carboplatin Versus the Chemotherapy Alone in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck Who Have Progressed on or After Prior Platinum-Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Squamous Cell of the Head and Neck
Keywords: carcinoma
squamous cell
head
neck
REOLYSIN (Reovirus Type 3 Dearing)
chemotherapy
Carboplatin
Paclitaxel
metastatic
recurrent
Lead sponsor: Oncolytics Biotech
Sponsor class: INDUSTRY
First posted: 2010-07-21
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this Phase 3 study is to evaluate overall survival and progression free survival following intravenous administration of REOLYSIN (Reovirus Serotype 3 Dearing) in combination with paclitaxel and carboplatin versus chemotherapy treatment alone, in patients with metastatic or recurrent Squamous Cell Carcinoma of the Head and Neck.

Detailed description: Squamous cell carcinoma of the head and neck is the sixth most common cancer in the world. More than 50% of patients diagnosed with advanced regional disease will relapse locally or at distant sites. Initial therapeutic options include irradiation, surgery and chemotherapy. The most commonly used agents are cisplatin and carboplatin, generally in combination with 5-FU or a taxane. Erbitux has been approved for use in first-line with radiation and in second-line as monotherapy. Only about a third of the patients will respond to first-line platinum-based therapy and the median overall survival is about 6-9 months.

Preliminary assessment of a Phase 1-2 study conducted in the UK investigating the combination of REOLYSIN, carboplatin and paclitaxel suggested that patients with head and neck carcinomas may represent a group of patients in whom this treatment combination is active. Studies have also shown that paclitaxel and carboplatin combination therapy may be effective in head and neck cancers, even in heavily pretreated patients and those resistant to previous treatment. These results strongly support the utility of the carboplatin/paclitaxel combination as a control arm for salvage therapy in platinum refractory patients, a patient group with few and poor treatment options and with no gold standard therapy.

This Phase 3 study is designed to compare response rates following intravenous administration of REOLYSIN (Reovirus Type 3 Dearing) in combination with paclitaxel and carboplatin versus chemotherapy treatment alone, in patients with metastatic or recurrent Squamous Cell Carcinoma of the Head and Neck.

Overall survival is a primary endpoint of this trial. Patients will be clinically evaluated after each course of treatment and radiologically every 6 weeks on and after treatment. The safety of the paclitaxel and carboplatin with intravenous blinded placebo or intravenous blinded REOLYSIN will also be assessed.

Eligibility criteria: Inclusion Criteria: Each patient MUST:

* have recurrent or metastatic (R/M) histologically confirmed squamous cell carcinoma (SCC) of the head and neck (oropharynx, oral cavity, larynx, hypopharynx) or squamous cell nasopharynx cancer (NPC) with distal metastasis(es) and no secondary cancers (Patients with NPC without distal metastasis(es) or with undifferentiated NPC are not eligible).
* have at least one lesion that is measurable by computed tomography or magnetic resonance imaging (Lesions persisting in previously treated radiation fields are considered not evaluable for response except if representing a relapse in a mucosal or nodal lesion that previously demonstrated a complete response. Any new lesion within the previous radiation fields is acceptable for determination of response and/or progression).
* have completed first line chemotherapy for R/M SCCHN which progressed on or within 190 days following the completion of platinum or platinum-based chemotherapy.
* have no continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures. Any surgery involving the SCC for which the patient is being treated (except biopsies) must have occurred at least 28 days prior to study enrollment.
* have received no chemotherapy, radiotherapy, immunotherapy or hormonal therapy within 28 days.
* have ECOG Performance Score of ≤ 2.
* have life expectancy of at least 3 months.
* absolute neutrophil count (ANC)≥ 1.5 x 10\^9/L ; platelets ≥100 x 10\^9/L\]; hemoglobin ≥9.0 g/dL; serum creatinine ≤1.5 xULN; bilirubin ≤1.5 x ULN; AST/ALT ≤2.5 x ULN.
* negative pregnancy test for females with childbearing potential.
* Be wiling and able to comply with scheduled visits, the treatment plan, and laboratory tests.

Exclusion Criteria: No patient may:

* receive concurrent therapy with any other investigational anticancer agent while on study.
* have been treated with a taxane for SCCHN.
* have current -- or with a history of -- brain metastases because of their poor prognosis and because of the frequent development of progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* be on chronic immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
* be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, be surgically sterile, or be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception.
* have clinically significant cardiac disease (New York Heart Association, Class III or IV) including, but not limited to, pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year prior to study entry.
* have dementia or any altered mental status that would prohibit informed consent.
* have any other acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.

Primary outcomes:
measure: Overall survival
timeFrame: every 3 months until death.
Secondary outcomes:
measure: Progression-free survival
timeFrame: Assessed every 6 weeks until disease progression or death.
measure: Objective response (complete response (CR) + partial response (PR)) rate and duration
timeFrame: Evaluation of response is conducted every 6 weeks on and after study. Duration of objective response is measured from the time measurement criteria are first met for CR or PR until recurrent or progressive disease is objectively documented.
measure: Number of participants with adverse events as a measure of safety and tolerability of REOLYSIN when administered in combination with paclitaxel and carboplatin.
timeFrame: Within 30 days of the last dose of REOLYSIN.
measure: Compare Best % Tumor Specific Response in loco-regional disease and/or metastatic disease for the treatment regimens in the study population
timeFrame: Assessed every 6 weeks until disease progression or death.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Burbank
country: United States
facility: Providence Health and Services
state: California
city: Corona
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Orange
country: United States
facility: BMS Physician Practice, A Medical Corporation DBA Medical Oncology Care Associates
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Port Richey
country: United States
facility: Pasco Hernando Oncology Associates, PA
state: Florida
city: Altanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Elk Grove Village
country: United States
facility: Alexian Brothers Hospital Network
state: Illinois
city: Baton Rouge
country: United States
facility: Mary Bird Perkinds Cancer Center - Baton Rouge
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center, University Hospitals Case Medical Center
state: Ohio
city: Toledo
country: United States
facility: Mercy Cancer Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Texas Oncology- Sammons Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center at UTHSCSA
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology
state: Washington
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame
state: Quebec
city: Bordeaux
country: France
facility: Hopital Saint-André / Service d'Oncologie-Radiothérapie
city: Nice
country: France
facility: Centre Antoine Lacassagne / Oncologie Médicale
city: Paris
country: France
facility: Institut Curie / Département d'Oncologie Médicale
city: Hamburg
country: Germany
facility: UKE Hamburg
city: Athens
country: Greece
facility: Attikon University Hospital
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Uzsoki Utcai Kórház
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem
city: Szegedi
country: Hungary
facility: Szegedi Tudományegyetem
city: Szombathely
country: Hungary
facility: Markusovszky Korhaz
city: Cuneo
country: Italy
facility: Ufficio Sperimentazioni Cliniche c/o S.C. Oncologia Medica
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale del Tumori
city: Milan
country: Italy
facility: Ospedale San Paolo - Oncologia Medica
city: Modena
country: Italy
facility: University Hospital in Modena
city: Krakow
country: Poland
facility: Centrum Onkologii - Instytyt im.M.Skłodowskiej-Curie
city: Olsztyn
country: Poland
facility: Szpital MSWiA - Centrum Onkologi
city: Poznań
country: Poland
facility: Wielkopolskie Centrum Onkologii
city: Łódź
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. M.Kopernika
city: Arkhangelsk
country: Russian Federation
facility: State Health Care Institution "Arkhangelsk Regional Clinical Oncology Dispensary"
city: Belgorod
country: Russian Federation
facility: Regional State Health Care Institution "Belgorod Oncology Dispensary"
city: Chelyabinsk
country: Russian Federation
facility: State Health Care Institution "Chelyabinsk Regional Oncology Dispensary"
city: Kazan
country: Russian Federation
facility: State Health Care Institution "Republican Clinical Oncology Dispensary of Ministry of Health of the Republic of Tatarstan"
city: Krasnodar
country: Russian Federation
facility: State Budgetary Health Care Institution "Clinical Oncology Dispensary #1" of Krasnodar Region Health Care Department
city: Kursk
country: Russian Federation
facility: Regional Budgetary Health Care Institution "Kursk Regional Oncology Dispensary" of Health Care Committee of Kursk region
city: Obninsk
country: Russian Federation
facility: Federal State Budgetary Institution "Medical Research Radiology Center" of Ministry of Public Health and Social Development of Russian Federation, Obninsk
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "Russian Research Centre of Radiology and Surgery technologies" of Ministry of Public Health and Social Development of the Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "N. N. Petrov Oncology Research Institute" of Ministry of Public Health and Social Development of the Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: St.Petersburg State Health Care Institution City Clinical Oncology Dispensary"
city: Sochi
country: Russian Federation
facility: State Health Care Institution "Oncology Dispensary №2" of Krasnodar Region Health Care Department
city: Tula
country: Russian Federation
facility: State Health Care Institution "Tula Regional Oncology Dispensary"
city: Ufa
country: Russian Federation
facility: State Budgetary Healthcare Institution "Republic Clinical Oncology Dispensary Ministry of Health of Bashkortostan"
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Health Care Institution of the Yaroslavl region "Regional Clinical Oncological Hospital"
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Barcelona
country: Spain
facility: Instituto Catlan de Oncologia (ICO) - Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Instituto Catlan de Oncologia (ICO) - Hospital Germans Trias I Pujol
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Center
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Leeds
country: United Kingdom
facility: St. James's University Hospital
city: London
country: United Kingdom
facility: Guy's and St. Thomas Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Cancer Center, Fulham Road branch
city: Sutton
country: United Kingdom
facility: The Royal Marsden Cancer Center, Sutton Branch
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
city: Whitchurch
country: United Kingdom
facility: The Velindre Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Foundation Trust
Study officials:
affiliation: University of Alabama at Birmingham, Birmingham, AB, US
name: James A Bonner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Royal Marsden Hospital, London, UK
name: Kevin Harrington, MBBS MRCP FRCR
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Antwerp, Belgium
name: Jan Vermorken, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: