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

NCT01161498 | Terminated Phase 3 Results DMC

• 2 other identifiers: 006/0920110130
• Study Type: interventional
• Target: 5
• Locations: 2 countries
• Sites: 6

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.

Conditions

Squamous Cell Carcinoma; Head and Neck Cancer

Keywords

squamous cell; OncoVEX^GM-CSF; Oncovex; chemoradiation; Cisplatin

Outcome Measures

Primary Outcomes (1)

• 2-year Event-free Survival

  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.

  2 years

Secondary Outcomes (9)

• 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 Locoregional Failure

  Up to 27 months

• Time to Distant Failure

  Up to 27 months

Study Arms (2)

Radiation/Cisplatin

ACTIVE COMPARATOR

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.

Radiation: Radiation; Drug: Cisplatin

Talimogene Laherparepvec + Radiation/Cisplatin

EXPERIMENTAL

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.

Biological: Talimogene Laherparepvec; Radiation: Radiation; Drug: Cisplatin

Interventions

Talimogene Laherparepvec BIOLOGICAL

Administered by intratumoral injection

Also known as: OncoVEX^GM-CSF, IMLYGIC

Talimogene Laherparepvec + Radiation/Cisplatin

Radiation RADIATION

70 grays of radiation administered in 35 fractions over 7 weeks

Radiation/Cisplatin; Talimogene Laherparepvec + Radiation/Cisplatin

Cisplatin DRUG

Administered by intravenous infusion

Radiation/Cisplatin; Talimogene Laherparepvec + Radiation/Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine clearance ≥ 60 mL/min
• 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.
• Male patients must agree to use a condom with spermicide or their female partner must use an effective method of birth control.

You may not qualify if:

• Prior treatment for locally advanced SCCHN (No prior surgery for SCCHN except nodal sampling or biopsy for study disease).
• Patients with T1-2N1 or T1N2-3.
• 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..
• High risk for poor compliance with therapy or follow up as assessed by the investigator.
• 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.
• Prior systemic chemotherapy for any type of cancer.
• Patients for whom radiation therapy is contraindicated.
• 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.

Sponsors & Collaborators

• BioVex Limited: lead
• Amgen: collaborator

Study Sites (6)

Investigative Clinical Research of Indiana

Indianapolis, Indiana, 46260, United States

Location

James Graham Brown Cancer Center, University of Louisville

Louisville, Kentucky, 40202, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Medical Univesity of South Carolina

Charleston, South Carolina, 29425, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

The Royal Marsden Hospital

London, London, SE1 7EH, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Head and Neck Neoplasms

Interventions

talimogene laherparepvec; Radiation; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Physical Phenomena; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen, Inc.

866-572-6436

Study Officials

• Kevin Harrington, MD

  Royal Marsden, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2010
• First Posted: July 13, 2010
• Study Start: February 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: February 8, 2016
• Results First Posted: December 17, 2015

Record last verified: 2016-01

Locations

GB (1); US (5)