Clinical trial NCT01161498: Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
Official title: A Phase 3 Randomized Trial of Concurrent Cisplatin & Radiotherapy With Or Without ONCOVEX^GM-CSF In Previously Untreated Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Squamous Cell Carcinoma
Head and Neck Cancer
Keywords: squamous cell
OncoVEX^GM-CSF
Oncovex
chemoradiation
Cisplatin
Lead sponsor: BioVex Limited
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2010-07-13
Enrollment: 5
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: 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.

Detailed description: The objective is to evaluate the efficacy and safety of treatment with chemoradiation (CRT) plus talimogene laherparepvec compared to CRT alone in previously untreated patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) for which surgical resection is not clinical indicated. The efficacy endpoints of the study aim to demonstrate overall clinical benefit for patients treated with talimogene laherparepvec as compared to CRT alone.

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.

Primary outcomes:
measure: 2-year Event-free Survival
timeFrame: 2 years
Secondary outcomes:
measure: Clinical Objective Response (cOR)
timeFrame: End of trial; the maximum time on study was 20 weeks.
measure: Metabolic Complete Response (mCR)
timeFrame: End of study; the maximum time on study was 20 weeks.
measure: Pathologic Complete Response (mCR)
timeFrame: Up to Week 20
measure: Time to Locoregional Failure
timeFrame: Up to 27 months
measure: Time to Distant Failure
timeFrame: Up to 27 months
measure: Time to Any Failure
timeFrame: Up to 27 months
measure: Overall Survival
timeFrame: Up to 5 years after chemoradiotherapy
measure: Disease-specific Survival
timeFrame: Up to 5 years after chemoradiotherapy
measure: Participants With N1-2 Disease at Baseline Requiring Neck Dissection
timeFrame: Weeks 19 - 21
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Investigative Clinical Research of Indiana
state: Indiana
city: Louisville
country: United States
facility: James Graham Brown Cancer Center, University of Louisville
state: Kentucky
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Charleston
country: United States
facility: Medical Univesity of South Carolina
state: South Carolina
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Royal Marsden, UK
name: Kevin Harrington, MD
role: PRINCIPAL_INVESTIGATOR
References: