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
Overview
- Phase
- Phase 3
- Intervention
- Radiation
- Conditions
- Squamous Cell Carcinoma
- Sponsor
- BioVex Limited
- Enrollment
- 5
- Locations
- 6
- Primary Endpoint
- 2-year Event-free Survival
- Status
- Terminated
- Last Updated
- 10 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female ≥ 18 years
- •Eastern Co-Operative Oncology Group (ECOG) Performance Status ≤ 1
- •Histological evidence (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
- •Stage III or IV disease (T2N2-3M0, T3-4N1-3M0)
- •No evidence of distant metastases by computed tomography (CT) or positron emission tomography (PET)/CT scan
- •Life expectancy \> 4 months
- •Neutrophil count ≥ 2,000/mm\^3
- •Platelet count ≥ 100,000/mm\^3
- •Hemoglobin ≥ 10 g/dL
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Exclusion Criteria
- •Prior treatment for locally advanced SCCHN (No prior surgery for SCCHN except nodal sampling or biopsy for study disease).
- •Patients with T1-2N1 or T1N2-
- •Pre-existing peripheral neuropathy ≥ Grade 2 (motor or sensory).
- •Weight loss \> 20% of body weight within 3 months of screening (unless purposeful).
- •Surgery ≤ 28 days before randomization with the exception of feeding tube placement, dental extractions, central venous catheter placement, biopsies and nodal sampling.
- •Cancer of the nasopharynx, sinus, salivary gland or skin.
- •Previous radical radiation therapy (RT) to the head and neck region, excluding superficial RT for a non-melanomatous skin cancer.
- •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.
- •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.
- •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..
Arms & Interventions
Radiation/Cisplatin
Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
Intervention: Radiation
Radiation/Cisplatin
Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
Intervention: Cisplatin
Talimogene Laherparepvec + Radiation/Cisplatin
The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Intervention: Talimogene Laherparepvec
Talimogene Laherparepvec + Radiation/Cisplatin
The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Intervention: Radiation
Talimogene Laherparepvec + Radiation/Cisplatin
The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Intervention: Cisplatin
Outcomes
Primary Outcomes
2-year Event-free Survival
Time Frame: 2 years
Event-free survival is defined as the time from randomization until the first evidence of relapse, disease progression (local, regional, metastatic, or second primary), or death from any cause. Because this study was terminated with only 5 participants enrolled, and the study was terminated in the first year, this endpoint was not analyzed.
Secondary Outcomes
- Clinical Objective Response (cOR)(End of trial; the maximum time on study was 20 weeks.)
- Metabolic Complete Response (mCR)(End of study; the maximum time on study was 20 weeks.)
- Pathologic Complete Response (mCR)(Up to Week 20)
- Time to Distant Failure(Up to 27 months)
- Time to Any Failure(Up to 27 months)
- Overall Survival(Up to 5 years after chemoradiotherapy)
- Disease-specific Survival(Up to 5 years after chemoradiotherapy)
- Time to Locoregional Failure(Up to 27 months)
- Participants With N1-2 Disease at Baseline Requiring Neck Dissection(Weeks 19 - 21)