Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects
- Conditions
- Oral Mucositis
- Interventions
- Biological: ALD518Drug: 0.9% saline
- Registration Number
- NCT01403064
- Lead Sponsor
- CSL Behring
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of ALD518 in modifying the course of oral mucositis in subjects with head and neck cancer receiving concomitant chemotherapy and radiotherapy
- Detailed Description
This was a Phase 2, placebo-controlled, double-blind study in subjects newly diagnosed with head and neck cancer (who had not received previous treatment for oral mucositis) and who were receiving concomitant chemotherapy and radiotherapy. Subject eligibility, including tumor staging, was assessed during the screening period, which was to occur within 30 days prior to the initiation of radiation therapy. The radiation therapy treatment period was approximately 7 weeks, depending on the subject's prescribed radiation plan. Prior to the randomized portion of the trial, the first 7 subjects enrolled in the study entered a safety run-in evaluation and received a total of 2 doses of open-label clazakizumab 160 mg IV, 4 weeks apart (Day 0 and Week 4 of radiation); these subjects were not eligible for the randomized portion of the study. Subsequent to completion of the safety run-in, eligible subjects were randomized 1:1:1 to treatment with 2 doses of clazakizumab 160 mg, or clazakizumab 320 mg, or placebo, administered IV 3 weeks apart (Day 0 and Week 3 of radiation therapy). All subjects were to be followed for 4 weeks post last day of radiotherapy treatment for the primary efficacy and safety assessments and then for up to an additional 12 months of long-term follow-up.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 76
- Have recently diagnosed (< than 6 months prior to screening visit date), pathologically confirmed, non-metastatic SCC of the oral cavity, oropharynx, hypopharynx or larynx that will be treated with CRT as first-line treatment; subjects with a history of surgical management (approximately 4-6 weeks before RT with sufficient time for post-surgical healing) are eligible
- Have a plan to receive a continuous course of conventional external beam irradiation delivered by intensity-modulated radiotherapy (IMRT) as single daily fractions of 2.0 to 2.2 Gy, with a cumulative radiation dose between 55 and 72 Gy.
- Have a plan to receive a standard cisplatin CT regimen administered tri-weekly (80 to 100 mg/m2, on Days 0, 21, and 42) or weekly (30 to 40 mg/m2) or a standard carboplatin regimen administered weekly (100 mg/m2)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- CRP < 80 mg/L
- Have adequate hematopoietic, hepatic, and renal function at the screening visit
- Tumor of the lips, sinuses, salivary glands, nasopharynx or unknown primary tumor
- Metastatic disease (M1) Stage IV C
- Any prior history of head and neck cancer
- Prior radiation to the head and neck
- Have had a major surgical procedure, other than for HNC, or significant traumatic injury within 4 weeks prior to the initiation of RT; or anticipation of need for a major surgical procedure during the clinical trial
- Active infectious disease, excluding oral candidiasis
- Have OM at the screening visit
- Have a history of hypersensitivity to monoclonal antibody
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open Label ALD518 ALD518 - ALD518 Dose 1 ALD518 - Placebo 0.9% saline - ALD518 Dose 2 ALD518 -
- Primary Outcome Measures
Name Time Method Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities Up to 15 months Number of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities Up to 15 months Percent of Participants With All Grades of Oral Mucositis (OM) at a Radiation Dose of 55 Gy Up to 12 weeks Gray (Gy) is used as a unit of the radiation quantity absorbed dose that measures the energy deposited by ionizing radiation in a unit mass of matter being irradiated, and is used for measuring the delivered dose of ionizing radiation in applications such as radiotherapy. The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy
Number of Participants With All Grades of OM at a Radiation Dose of 55 Gy Up to 12 weeks The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy
- Secondary Outcome Measures
Name Time Method Time to Onset of Ulcerative and Severe OM Up to 12 weeks Percent of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy) Up to 12 weeks The ulcerative OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy
Percent of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy) Measured from onset of OM through Week 12 The severe OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first severe OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy
Number of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy) Up to 12 weeks The severe OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first severe OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy
Number of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy) Up to 12 weeks The ulcerative OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy
Duration of Ulcerative and Severe OM Up to 12 weeks ALD518 Plasma Concentration at Varying Weeks Baseline and up to 12 weeks Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN) Questionnaire Overall Assessment Score at Varying Cumulative Radiation Doses (Gy) Baseline and up to 12 weeks The FACT-HN consists of 28 general + 11 head and neck specific items, each rated on a 0 (not at all) to 4 (very much) Likert type scale. The total score ranges from 0 to 148. Higher scores represent better quality of life.
Functional Assessment of Chronic Illness Therapy - Fatigue Questionnaire (FACIT-F) Score at Varying Cumulative Radiation Doses (Gy) Baseline and up to 12 weeks The responses to the 13 items on the FACIT-F questionnaire are each measured on a 5-point Likert scale from 0 (not at all fatigued) to 4 (very much fatigued). The total score ranges from 0 to 52. Higher scores represent less fatigue.
Oral Mucositis Daily Questionnaire (OMDQ) Overall Health Score at Varying Cumulative Radiation Doses (Gy) Baseline and up to 12 weeks Scored on a scale from 0 (worst possible overall health) to 10 (perfect overall health). Higher scores represent better overall health.
Mean Change From Baseline in C-reactive Protein (CRP) Values at Varying Weeks Baseline and up to 12 weeks The level of C-reactive protein (CRP), which can be measured in your blood, increases when there's inflammation in your body.
Trial Locations
- Locations (31)
Morton Plant Mease Health Care
🇺🇸Clearwater, Florida, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Cancer Specialists of Southern Texas
🇺🇸Corpus Christi, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Adelaide Radiotherapy Centre
🇦🇺Adelaide, South Australia, Australia
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
VA Puget Sound Health Care Syatem
🇺🇸Seattle, Washington, United States
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Univ. Klinik fur Innere Medizin III
🇦🇹Salzburg, Austria
Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
CHUQ-L'Hotel-Dieu de Quebec
🇨🇦Quebec, Canada
LKH Graz, HNO Ambulanz
🇦🇹Graz, Austria
Detroit Clinical Research Center
🇺🇸Farmington Hills, Michigan, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
St. Vincent's Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Hanusch Krankenhaus
🇦🇹Vienna, Austria
Royale Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Cancer Centre of Southeastern Ontario
🇨🇦Kingston, Ontario, Canada
Maisonneuve-Rosemont Hospital
🇨🇦Montreal, Quebec, Canada
Uniklinik Koln
🇩🇪Koln, Germany
Universitatsklinikum Freiburg
🇩🇪Freiburg, Germany
A.O. San Paolo - Polo Universitario
🇮🇹Milan, Italy
University Medical School, Saarland
🇩🇪Homburg, Germany
Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
🇮🇹Udine, Italy
Istituto Nazionale dei tumari
🇮🇹Milan, Italy