Efficacy Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Platinum-Refractory Head and Neck Cancers

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Squamous Cell of the Head and Neck
• Intervention / Treatment: Drug: Placebo; Drug: Carboplatin; Drug: Paclitaxel; Biological: REOLYSIN

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.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
    • ZNA Middelheim
  • Edegem, Belgium
    • University Hospital Antwerp
  • Jette, Belgium, 1090
    • Universitair Ziekenhuis Brussel
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Center
    • London, Ontario, Canada, N6A 4L6
      • London Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Hôpital Notre-Dame
• France
  • Bordeaux, France, 33075
    • Hopital Saint-André / Service d'Oncologie-Radiothérapie
  • Nice, France, 06189
    • Centre Antoine Lacassagne / Oncologie Médicale
  • Paris, France, 75248
    • Institut Curie / Département d'Oncologie Médicale
• Germany
  • Hamburg, Germany
    • UKE Hamburg
• Greece
  • Athens, Greece
    • Attikon University Hospital
• Hungary
  • Budapest, Hungary
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary
    • Fövárosi Önkormányzat uzsoki utcai Kórház
  • Pecs, Hungary
    • Pecsi Tudomanyegyetem
  • Szegedi, Hungary
    • Szegedi Tudomanyegyetem
  • Szombathely, Hungary
    • Markusovszky Korhaz
• Italy
  • Cuneo, Italy
    • Ufficio Sperimentazioni Cliniche c/o S.C. Oncologia Medica
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale del Tumori
  • Milan, Italy
    • Ospedale San Paolo - Oncologia Medica
  • Modena, Italy
    • University Hospital in Modena
• Poland
  • Krakow, Poland
    • Centrum Onkologii - Instytyt im.M.Skłodowskiej-Curie
  • Olsztyn, Poland
    • Szpital MSWiA - Centrum Onkologi
  • Poznań, Poland
    • Wielkopolskie Centrum Onkologii
  • Łódź, Poland
    • Wojewodzki Szpital Specjalistyczny im. M.Kopernika
• Russian Federation
  • Arkhangelsk, Russian Federation
    • State Health Care Institution "Arkhangelsk Regional Clinical Oncology Dispensary"
  • Belgorod, Russian Federation
    • Regional State Health Care Institution "Belgorod Oncology Dispensary"
  • Chelyabinsk, Russian Federation
    • State Health Care Institution "Chelyabinsk Regional Oncology Dispensary"
  • Kazan, Russian Federation
    • State Health Care Institution "Republican Clinical Oncology Dispensary of Ministry of Health of the Republic of Tatarstan"
  • Krasnodar, Russian Federation
    • State Budgetary Health Care Institution "Clinical Oncology Dispensary #1" of Krasnodar Region Health Care Department
  • Kursk, Russian Federation
    • Regional Budgetary Health Care Institution "Kursk Regional Oncology Dispensary" of Health Care Committee of Kursk region
  • Obninsk, Russian Federation
    • Federal State Budgetary Institution "Medical Research Radiology Center" of Ministry of Public Health and Social Development of Russian Federation, Obninsk
  • Saint Petersburg, Russian Federation
    • Federal State Budgetary Institution "Russian Research Centre of Radiology and Surgery technologies" of Ministry of Public Health and Social Development of the Russian Federation
  • Saint-Petersburg, Russian Federation
    • Federal State Budgetary Institution "N. N. Petrov Oncology Research Institute" of Ministry of Public Health and Social Development of the Russian Federation
  • Saint-Petersburg, Russian Federation
    • St.Petersburg State Health Care Institution City Clinical Oncology Dispensary"
  • Sochi, Russian Federation
    • State Health Care Institution "Oncology Dispensary №2" of Krasnodar Region Health Care Department
  • Tula, Russian Federation
    • State Health Care Institution "Tula Regional Oncology Dispensary"
  • Ufa, Russian Federation
    • State Budgetary Healthcare Institution "Republic Clinical Oncology Dispensary Ministry of Health of Bashkortostan"
  • Yaroslavl, Russian Federation
    • State Budgetary Health Care Institution of the Yaroslavl region "Regional Clinical Oncological Hospital"
• Slovenia
  • Ljubljana, Slovenia
    • Institute of Oncology Ljubljana
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08908
    • Instituto Catlan de Oncologia (ICO) - Hospital Duran i Reynals
  • Barcelona, Spain
    • Instituto Catlan de Oncologia (ICO) - Hospital Germans Trias I Pujol
  • Bilbao, Spain
    • Hospital de Basurto
  • Pamplona, Spain
    • Hospital de Navarra
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Center
  • Guildford, United Kingdom, GU2 7WG
    • Royal Surrey County Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St. James's University Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's and St. Thomas Hospital
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Cancer Center, Fulham Road branch
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Cancer Center, Sutton Branch
  • Taunton, United Kingdom, TA1 5DA
    • Musgrove Park Hospital
  • Whitchurch, United Kingdom, CF14 2TL
    • The Velindre Hospital
  • Wirral, United Kingdom, CH634JY
    • Clatterbridge Centre for Oncology NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Arizona Oncology Associates
  • California
    • Burbank, California, United States, 91505
      • Providence Health and Services
    • Corona, California, United States, 92879
      • Wilshire Oncology Medical Group
    • Orange, California, United States, 92868
      • BMS Physician Practice, A Medical Corporation DBA Medical Oncology Care Associates
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Florida
    • New Port Richey, Florida, United States, 34652
      • Pasco Hernando Oncology Associates, PA
  • Georgia
    • Altanta, Georgia, United States, 30322
      • Emory University - Winship Cancer Institute
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Hospital Network
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkinds Cancer Center - Baton Rouge
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Nevada
    • Las Vegas, Nevada, United States, 59169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Comprehensive Cancer Center, University Hospitals Case Medical Center
    • Toledo, Ohio, United States, 43623
      • Mercy Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology- Sammons Cancer Center
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center at UTHSCSA
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Washington
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology and Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: REOLYSIN, paclitaxel, carboplatin	Drug: Carboplatin; 5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle; Drug: Paclitaxel; 175 mg/m2, 3 hour intravenous infusion, given on Day 1 of a 21 day cycle; Biological: REOLYSIN; 3E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle; Other Names: reovirus serotype 3 Dearing Strain
Placebo Comparator: placebo, paclitaxel, carboplatin	Drug: Placebo; Placebo; Drug: Carboplatin; 5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle; Drug: Paclitaxel; 175 mg/m2, 3 hour intravenous infusion, given on Day 1 of a 21 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	every 3 months until death.

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Assessed every 6 weeks until disease progression or death.
Objective response (complete response (CR) + partial response (PR)) rate and duration	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.
Number of participants with adverse events as a measure of safety and tolerability of REOLYSIN when administered in combination with paclitaxel and carboplatin.	Within 30 days of the last dose of REOLYSIN.
Compare Best % Tumor Specific Response in loco-regional disease and/or metastatic disease for the treatment regimens in the study population	Assessed every 6 weeks until disease progression or death.

Collaborators and Investigators

• Sponsor: Oncolytics Biotech
• Investigators: Principal Investigator: James A Bonner, MD, University of Alabama at Birmingham, Birmingham, AB, US; Principal Investigator: Kevin Harrington, MBBS MRCP FRCR, The Royal Marsden Hospital, London, UK; Principal Investigator: Jan Vermorken, MD, PhD, University Hospital, Antwerp, Belgium

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: July 13, 2010
• First Submitted That Met QC Criteria: July 19, 2010
• First Posted (Estimate): July 21, 2010

Study Record Updates

• Last Update Posted (Estimate): November 5, 2014
• Last Update Submitted That Met QC Criteria: November 3, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: chemotherapy; carcinoma; Carboplatin; metastatic; Paclitaxel; head; neck; recurrent; squamous cell; REOLYSIN (Reovirus Type 3 Dearing)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: REO 018