Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects

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

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

Study Overview

• Status: Terminated
• Conditions: Oral Mucositis
• Intervention / Treatment: Biological: ALD518; Drug: 0.9% saline

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.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royale Brisbane and Women's Hospital
    • Woolloongabba, Queensland, Australia
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
    • Adelaide, South Australia, Australia, 5037
      • Adelaide Radiotherapy Centre
• Austria
  • Graz, Austria
    • LKH Graz, HNO Ambulanz
  • Salzburg, Austria, 5020
    • Univ. Klinik fur Innere Medizin III
  • Vienna, Austria, 1140
    • Hanusch Krankenhaus
• Canada
  • Quebec, Canada, G1R 2J6
    • CHUQ-L'Hotel-Dieu de Quebec
  • Ontario
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
• Germany
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg
  • Homburg, Germany, 66424
    • University Medical School, Saarland
  • Koln, Germany, 50924
    • Uniklinik Koln
• Italy
  • Milan, Italy, 20142
    • A.O. San Paolo - Polo Universitario
  • Milan, Italy
    • Istituto Nazionale dei tumari
  • Udine, Italy, 33100
    • Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
• United States
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Mease Health Care
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Center
    • Farmington Hills, Michigan, United States, 48336
      • Detroit Clinical Research Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
  • Texas
    • Corpus Christi, Texas, United States, 78412
      • Cancer Specialists of Southern Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care Syatem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: 0.9% saline; IV Infusion
Experimental: Open Label ALD518	Biological: ALD518; IV
Experimental: ALD518 Dose 1	Biological: ALD518; IV
Experimental: ALD518 Dose 2	Biological: ALD518; IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Up to 12 weeks
Number of Participants With All Grades of OM at a Radiation Dose of 55 Gy	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	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)	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	Up to 12 weeks
Number of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)	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	Up to 12 weeks
Percent of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)	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	Measured from onset of OM through Week 12
Number of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)	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	Up to 12 weeks
Duration of Ulcerative and Severe OM		Up to 12 weeks
Time to Onset of Ulcerative and Severe OM		Up to 12 weeks
ALD518 Plasma Concentration at Varying Weeks		Baseline and up to 12 weeks
Oral Mucositis Daily Questionnaire (OMDQ) Overall Health Score at Varying Cumulative Radiation Doses (Gy)	Scored on a scale from 0 (worst possible overall health) to 10 (perfect overall health). Higher scores represent better overall health.	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)	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.	Baseline and up to 12 weeks
Functional Assessment of Chronic Illness Therapy - Fatigue Questionnaire (FACIT-F) Score at Varying Cumulative Radiation Doses (Gy)	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.	Baseline and up to 12 weeks
Mean Change From Baseline in C-reactive Protein (CRP) Values at Varying Weeks	The level of C-reactive protein (CRP), which can be measured in your blood, increases when there's inflammation in your body.	Baseline and up to 12 weeks

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Jeffrey Smith, MD FRCP, Alder Biopharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: July 25, 2011
• First Submitted That Met QC Criteria: July 25, 2011
• First Posted (Estimate): July 27, 2011

Study Record Updates

• Last Update Posted (Actual): May 11, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Oral mucositis; head and neck cancer; chemotherapy; radiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Head and Neck Neoplasms; Mucositis; Stomatitis
• Other Study ID Numbers: ALD518-CLIN-009