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

Oral Mucositis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01403064
• Other study ID #: ALD518-CLIN-009
• Status: Terminated
• Phase: Phase 2
• Start date: July 2011
• Est. completion date: March 2014

Study information

• Verified date: April 2021
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Terminated
• Enrollment: 76
• Est. completion date: March 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Neoplasms
• Mucositis
• Oral Mucositis
• Stomatitis

Intervention

Biological:
• ALD518
IV

Drug:
• 0.9% saline
IV Infusion

Locations

Country	Name	City	State
Australia	Adelaide Radiotherapy Centre	Adelaide	South Australia
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	St. Vincent's Hospital	Darlinghurst	New South Wales
Australia	Royale Brisbane and Women's Hospital	Herston	Queensland
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	LKH Graz, HNO Ambulanz	Graz
Austria	Univ. Klinik fur Innere Medizin III	Salzburg
Austria	Hanusch Krankenhaus	Vienna
Canada	Cancer Centre of Southeastern Ontario	Kingston	Ontario
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	CHUQ-L'Hotel-Dieu de Quebec	Quebec
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	University Medical School, Saarland	Homburg
Germany	Uniklinik Koln	Koln
Italy	A.O. San Paolo - Polo Universitario	Milan
Italy	Istituto Nazionale dei tumari	Milan
Italy	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia	Udine
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Morton Plant Mease Health Care	Clearwater	Florida
United States	Cancer Specialists of Southern Texas	Corpus Christi	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Karmanos Cancer Center	Detroit	Michigan
United States	Detroit Clinical Research Center	Farmington Hills	Michigan
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Mount Sinai School of Medicine	New York	New York
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	VA Puget Sound Health Care Syatem	Seattle	Washington
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities		Up to 15 months
Primary	Number of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities		Up to 15 months
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of Ulcerative and Severe OM		Up to 12 weeks
Secondary	Time to Onset of Ulcerative and Severe OM		Up to 12 weeks
Secondary	ALD518 Plasma Concentration at Varying Weeks		Baseline and up to 12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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