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

Carcinoma, Squamous Cell of the Head and Neck Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01166542
• Other study ID #: REO 018
• Status: Completed
• Phase: Phase 3
• First received: July 13, 2010
• Last updated: November 3, 2014
• Start date: June 2010
• Est. completion date: May 2014

Study information

• Verified date: November 2014
• Source: Oncolytics Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyBelgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: May 2014
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Carcinoma, Squamous Cell of the Head and Neck

Intervention

Biological:
• REOLYSIN
3E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle

Drug:
• Carboplatin
5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle
• Paclitaxel
175 mg/m2, 3 hour intravenous infusion, given on Day 1 of a 21 day cycle
• Placebo
Placebo

Locations

Country	Name	City	State
Belgium	ZNA Middelheim	Antwerpen
Belgium	University Hospital Antwerp	Edegem
Belgium	Universitair Ziekenhuis Brussel	Jette
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Juravinski Cancer Center	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Hopital Notre-Dame	Montreal	Quebec
France	Hopital Saint-André / Service d'Oncologie-Radiothérapie	Bordeaux
France	Centre Antoine Lacassagne / Oncologie Médicale	Nice
France	Institut Curie / Département d'Oncologie Médicale	Paris
Germany	UKE Hamburg	Hamburg
Greece	Attikon University Hospital	Athens
Hungary	Fovarosi Onkormanyzat Uzsoki Utcai Kórház	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Pecsi Tudomanyegyetem	Pecs
Hungary	Szegedi Tudományegyetem	Szegedi
Hungary	Markusovszky Korhaz	Szombathely
Italy	Ufficio Sperimentazioni Cliniche c/o S.C. Oncologia Medica	Cuneo
Italy	Fondazione IRCCS Istituto Nazionale del Tumori	Milan
Italy	Ospedale San Paolo - Oncologia Medica	Milan
Italy	University Hospital in Modena	Modena
Poland	Centrum Onkologii - Instytyt im.M.Sklodowskiej-Curie	Krakow
Poland	Wojewódzki Szpital Specjalistyczny im. M.Kopernika	Lódz
Poland	Szpital MSWiA - Centrum Onkologi	Olsztyn
Poland	Wielkopolskie Centrum Onkologii	Poznan
Russian Federation	State Health Care Institution "Arkhangelsk Regional Clinical Oncology Dispensary"	Arkhangelsk
Russian Federation	Regional State Health Care Institution "Belgorod Oncology Dispensary"	Belgorod
Russian Federation	State Health Care Institution "Chelyabinsk Regional Oncology Dispensary"	Chelyabinsk
Russian Federation	State Health Care Institution "Republican Clinical Oncology Dispensary of Ministry of Health of the Republic of Tatarstan"	Kazan
Russian Federation	State Budgetary Health Care Institution "Clinical Oncology Dispensary #1" of Krasnodar Region Health Care Department	Krasnodar
Russian Federation	Regional Budgetary Health Care Institution "Kursk Regional Oncology Dispensary" of Health Care Committee of Kursk region	Kursk
Russian Federation	Federal State Budgetary Institution "Medical Research Radiology Center" of Ministry of Public Health and Social Development of Russian Federation, Obninsk	Obninsk
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"	Saint-Petersburg
Russian Federation	State Health Care Institution "Oncology Dispensary ?2" of Krasnodar Region Health Care Department	Sochi
Russian Federation	State Health Care Institution "Tula Regional Oncology Dispensary"	Tula
Russian Federation	State Budgetary Healthcare Institution "Republic Clinical Oncology Dispensary Ministry of Health of Bashkortostan"	Ufa
Russian Federation	State Budgetary Health Care Institution of the Yaroslavl region "Regional Clinical Oncological Hospital"	Yaroslavl
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Santa Creu I Sant Pau	Barcelona
Spain	Hospital Vall D'Hebron	Barcelona
Spain	Instituto Catlan de Oncologia (ICO) - Hospital Duran i Reynals	Barcelona
Spain	Instituto Catlan de Oncologia (ICO) - Hospital Germans Trias I Pujol	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	Hospital de Navarra	Pamplona
United Kingdom	Beatson West of Scotland Cancer Center	Glasgow
United Kingdom	Royal Surrey County Hospital	Guildford
United Kingdom	St. James's University Hospital	Leeds
United Kingdom	Guy's and St. Thomas Hospital	London
United Kingdom	The Royal Marsden Cancer Center, Fulham Road branch	London
United Kingdom	The Royal Marsden Cancer Center, Sutton Branch	Sutton
United Kingdom	Musgrove Park Hospital	Taunton
United Kingdom	The Velindre Hospital	Whitchurch
United Kingdom	Clatterbridge Centre for Oncology NHS Foundation Trust	Wirral
United States	Emory University - Winship Cancer Institute	Altanta	Georgia
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Mary Bird Perkinds Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Providence Health and Services	Burbank	California
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Case Comprehensive Cancer Center, University Hospitals Case Medical Center	Cleveland	Ohio
United States	Wilshire Oncology Medical Group	Corona	California
United States	Texas Oncology- Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Alexian Brothers Hospital Network	Elk Grove Village	Illinois
United States	Columbia Basin Hematology and Oncology	Kennewick	Washington
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Pasco Hernando Oncology Associates, PA	New Port Richey	Florida
United States	BMS Physician Practice, A Medical Corporation DBA Medical Oncology Care Associates	Orange	California
United States	Cancer Therapy and Research Center at UTHSCSA	San Antonio	Texas
United States	Mercy Cancer Center	Toledo	Ohio
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Oncolytics Biotech

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Greece,  Hungary,  Italy,  Poland,  Russian Federation,  Slovenia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		every 3 months until death.	No
Secondary	Progression-free survival		Assessed every 6 weeks until disease progression or death.	No
Secondary	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.	No
Secondary	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.	Yes
Secondary	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.	No