Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
Condition: Squamous Cell Carcinoma; Head and Neck Cancer
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms
Intervention: Talimogene Laherparepvec; Radiation; Cisplatin
Intervention description: Administered by intratumoral injection; 70 grays of radiation administered in 35 fractions over 7 weeks; Administered by intravenous infusion
Intervention MeSH terms: Talimogene laherparepvec
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: squamous cell; OncoVEX^GM-CSF; Oncovex; chemoradiation; Cisplatin

Summary:

      This study is being conducted to learn about the safety and risks of using talimogene
      laherparepvec to treat patients with head and neck cancer and to see if talimogene
      laherparepvec and chemoradiation together can destroy the tumours versus the use of
      chemoradiation alone. This study may provide information on the usefulness of talimogene
      laherparepvec combined with chemoradiation as a future treatment for head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female ≥ 18 years

          2. Eastern Co-Operative Oncology Group (ECOG) Performance Status ≤ 1

          3. Histological evidence (from the primary lesion and/or lymph nodes) of squamous cell
             carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx

          4. Stage III or IV disease (T2N2-3M0, T3-4N1-3M0)

          5. No evidence of distant metastases by computed tomography (CT) or positron emission
             tomography (PET)/CT scan

          6. Life expectancy > 4 months

          7. Neutrophil count ≥ 2,000/mm^3

          8. Platelet count ≥ 100,000/mm^3

          9. Hemoglobin ≥ 10 g/dL

         10. Bilirubin ≤ 1.5 times upper limit of normal (ULN)

         11. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN

         12. Alkaline phosphatase ≤ 2.5 times ULN

         13. Creatinine clearance ≥ 60 mL/min

         14. Female patients of child-bearing potential (i.e. not surgically sterile, or not having
             spontaneous amenorrhea for at least 12 months) must agree to use an effective form of
             contraception during the treatment phase of the study.

         15. Male patients must agree to use a condom with spermicide or their female partner must
             use an effective method of birth control.

         16. Provide written informed consent in accordance with all applicable regulations and
             follow the study procedures. Patients must be capable of understanding the
             investigational nature, potential risks and benefits of the study.

        Exclusion Criteria:

          1. Prior treatment for locally advanced SCCHN (No prior surgery for SCCHN except nodal
             sampling or biopsy for study disease).

          2. Patients with T1-2N1 or T1N2-3.

          3. Pre-existing peripheral neuropathy ≥ Grade 2 (motor or sensory).

          4. Weight loss > 20% of body weight within 3 months of screening (unless purposeful).

          5. Surgery ≤ 28 days before randomization with the exception of feeding tube placement,
             dental extractions, central venous catheter placement, biopsies and nodal sampling.

          6. Cancer of the nasopharynx, sinus, salivary gland or skin.

          7. Previous radical radiation therapy (RT) to the head and neck region, excluding
             superficial RT for a non-melanomatous skin cancer.

          8. Prior cancers, except: those diagnosed > 5 years ago with no evidence of disease
             recurrence and clinical expectation of recurrence of less than 5%; or successfully
             treated non-melanoma skin cancer; or carcinoma in situ of the cervix.

          9. Significant intercurrent illness that will interfere with the chemotherapy or
             radiation therapy such as human immunodeficiency (HIV) infection, cardiac failure,
             pulmonary compromise (chronic obstructive pulmonary disease, pneumonia or respiratory
             decompensation) resulting in hospitalization within 12 months of screening, or active
             infection.

         10. Any significant cardiac disease (e.g., New York Heart Association (NYHA) Class 3 or 4;
             myocardial infarction within the past 6 months; unstable angina; coronary angioplasty
             or coronary artery bypass graft (CABG) within the past 6 months; or uncontrolled
             atrial or ventricular cardiac arrhythmias..

         11. High risk for poor compliance with therapy or follow up as assessed by the
             investigator.

         12. Active herpes labialis, other lesions due to herpes simplex virus type I (HSV1) or
             dermatoses involving or within 50 cm of the lesions to be injected; active HSV1
             lesions must have resolved before talimogene laherparepvec is injected.

         13. Prior systemic chemotherapy for any type of cancer.

         14. Patients for whom radiation therapy is contraindicated.

         15. Pregnant or breast-feeding female. Confirmation that women of child-bearing potential
             are not pregnant. A negative serum β- human chorionic gonadotropin (β-hCG) pregnancy
             test result must be obtained during the screening period.

         16. Currently enrolled and receiving an investigational agent in a clinical research study
             or received an investigational agent for any reason within 4 weeks prior to screening.

         17. Require intermittent or chronic treatment with an anti-herpetic drug (e.g.,
             acyclovir), other than intermittent topical use.