Clinical trial NCT01403064: Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects
Official title: A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of ALD518 in the Reduction of Oral Mucositis in Subjects With Head and Neck Cancer Receiving Concomitant Chemotherapy and Radiotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Oral Mucositis
Keywords: Oral mucositis; head and neck cancer; chemotherapy; radiotherapy
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2011-07-27
Enrollment: 76
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: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities
timeFrame: Up to 15 months
measure: Number of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities
timeFrame: Up to 15 months
measure: Percent of Participants With All Grades of Oral Mucositis (OM) at a Radiation Dose of 55 Gy
timeFrame: Up to 12 weeks
measure: Number of Participants With All Grades of OM at a Radiation Dose of 55 Gy
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Percent of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)
timeFrame: Up to 12 weeks
measure: Number of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)
timeFrame: Up to 12 weeks
measure: Percent of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)
timeFrame: Measured from onset of OM through Week 12
measure: Number of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)
timeFrame: Up to 12 weeks
measure: Duration of Ulcerative and Severe OM
timeFrame: Up to 12 weeks
measure: Time to Onset of Ulcerative and Severe OM
timeFrame: Up to 12 weeks
measure: ALD518 Plasma Concentration at Varying Weeks
timeFrame: Baseline and up to 12 weeks
measure: Oral Mucositis Daily Questionnaire (OMDQ) Overall Health Score at Varying Cumulative Radiation Doses (Gy)
timeFrame: Baseline and up to 12 weeks
measure: Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN) Questionnaire Overall Assessment Score at Varying Cumulative Radiation Doses (Gy)
timeFrame: Baseline and up to 12 weeks
measure: Functional Assessment of Chronic Illness Therapy - Fatigue Questionnaire (FACIT-F) Score at Varying Cumulative Radiation Doses (Gy)
timeFrame: Baseline and up to 12 weeks
measure: Mean Change From Baseline in C-reactive Protein (CRP) Values at Varying Weeks
timeFrame: Baseline and up to 12 weeks
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Morton Plant Mease Health Care
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Corpus Christi
country: United States
facility: Cancer Specialists of Southern Texas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: VA Puget Sound Health Care Syatem
state: Washington
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Herston
country: Australia
facility: Royale Brisbane and Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Adelaide Radiotherapy Centre
state: South Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Graz
country: Austria
facility: LKH Graz, HNO Ambulanz
city: Salzburg
country: Austria
facility: Univ. Klinik fur Innere Medizin III
city: Vienna
country: Austria
facility: Hanusch Krankenhaus
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Quebec
country: Canada
facility: CHUQ-L'Hotel-Dieu de Quebec
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Homburg
country: Germany
facility: University Medical School, Saarland
city: Koln
country: Germany
facility: Uniklinik Koln
city: Milan
country: Italy
facility: A.O. San Paolo - Polo Universitario
city: Milan
country: Italy
facility: Istituto Nazionale dei tumari
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
Study officials:
affiliation: Alder Biopharmaceuticals, Inc.
name: Jeffrey Smith, MD FRCP
role: STUDY_DIRECTOR
References: