Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer

NCT ID: NCT01161498

Last Updated: 2016-02-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2011-10-31

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.

Conditions

Squamous Cell Carcinoma; Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Radiation

Intervention Type: RADIATION

70 grays of radiation administered in 35 fractions over 7 weeks

Cisplatin

Intervention Type: DRUG

Administered by intravenous infusion

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.

Group Type: EXPERIMENTAL

Talimogene Laherparepvec

Intervention Type: BIOLOGICAL

Administered by intratumoral injection

Radiation

Intervention Type: RADIATION

70 grays of radiation administered in 35 fractions over 7 weeks

Cisplatin

Intervention Type: DRUG

Administered by intravenous infusion

Interventions

Talimogene Laherparepvec

Administered by intratumoral injection

Intervention Type: BIOLOGICAL

Radiation

70 grays of radiation administered in 35 fractions over 7 weeks

Intervention Type: RADIATION

Cisplatin

Administered by intravenous infusion

Intervention Type: DRUG

Other Intervention Names

OncoVEX^GM-CSF; IMLYGIC

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

BioVex Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Harrington, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden, UK

Locations

Investigative Clinical Research of Indiana

Indianapolis, Indiana, United States

James Graham Brown Cancer Center, University of Louisville

Louisville, Kentucky, United States

Gabrail Cancer Center

Canton, Ohio, United States

Medical Univesity of South Carolina

Charleston, South Carolina, United States

VCU Massey Cancer Center

Richmond, Virginia, United States

The Royal Marsden Hospital

London, London, United Kingdom

Countries

United States; United Kingdom

Other Identifiers

20110130

Identifier Type: OTHER

Identifier Source: secondary_id

006/09

Identifier Type: -

Identifier Source: org_study_id