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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Oncolytics Biotech
ClinicalTrials.gov Identifier:
NCT01166542
First received: July 13, 2010
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Carcinoma, Squamous Cell of the Head and Neck
Biological: REOLYSIN
Drug: Carboplatin
Drug: Paclitaxel
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Oncolytics Biotech:

Primary Outcome Measures:
  • Overall survival [ Time Frame: every 3 months until death. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Assessed every 6 weeks until disease progression or death. ] [ Designated as safety issue: No ]
  • Objective response (complete response (CR) + partial response (PR)) rate and duration [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • Number of participants with adverse events as a measure of safety and tolerability of REOLYSIN when administered in combination with paclitaxel and carboplatin. [ Time Frame: Within 30 days of the last dose of REOLYSIN. ] [ Designated as safety issue: Yes ]
  • Compare Best % Tumor Specific Response in loco-regional disease and/or metastatic disease for the treatment regimens in the study population [ Designated as safety issue: No ]

Estimated Enrollment: 280
Study Start Date: June 2010
Study Completion Date: May 2014
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: REOLYSIN, paclitaxel, carboplatin Biological: REOLYSIN
3E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle
Other Name: reovirus serotype 3 Dearing Strain
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
Placebo Comparator: placebo, 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
Drug: Placebo
Placebo

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01166542

  Show 77 Study Locations
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Oncolytics Biotech
ClinicalTrials.gov Identifier: NCT01166542     History of Changes
Other Study ID Numbers: REO 018
Study First Received: July 13, 2010
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Oncolytics Biotech:
carcinoma
squamous cell
head
neck
REOLYSIN (Reovirus Type 3 Dearing)
chemotherapy
Carboplatin
Paclitaxel
metastatic
recurrent

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014