Cobiprostone for the Prevention of Oral Mucositis in Subjects With Head and Neck Cancer Receiving Concurrent Radiation and Chemotherapy

Study Overview
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Brief Summary
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Treatment for head and neck cancer often involves a combination of chemotherapy and radiation. One of the unfortunate consequences of standard care for head and neck cancer is the development of painful mouth sores, known as oral mucositis. This study will evaluate the use of cobiprostone spray to prevent oral mucositis, when given for the duration of radiation and chemotherapy (RT/CT) standard care.

Official Title
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A Multicenter, Randomized, Placebo-controlled, Double-blinded Study of the Efficacy, Safety, and Pharmacokinetics of Cobiprostone for the Prevention of Severe Oral Mucositis in Subjects With Head and Neck Cancer (HNC)

Conditions
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Oral Mucositis

Intervention / Treatment
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* Drug: Cobiprostone
* Drug: Placebo
* Drug: Standard Care - Chemotherapy
* Radiation: Standard Care - Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recently-diagnosed (within the last 6 months), histologically-documented, non-metastatic squamous cell carcinoma of the oral cavity and/or oropharynx amenable to radiotherapy with concurrent chemotherapy as the definitive treatment modality. Clinical treatment plan calls for a minimum of 50 Gy cumulative radiation dose administered via continuous course of external beam irradiation to the oral cavity and/or oropharynx via intensity-modulated radiation therapy (IMRT) and/or image-guided radiation therapy (IGRT), combined with conventional or weekly/tri-weekly cisplatin or carboplatin chemotherapy regimen. Exclusion Criteria: Subject has received prior radiation to the head and neck region (+/- chemotherapy). Subject has had any other prior invasive malignancy, unless disease-free for a minimum of 3 years. Subject has metastatic disease (M1) Stage IV-C. Subject has a presence of mucosal ulceration or oral mucositis at screening or develops this prior to randomization, and/or has unhealed wounds remaining from surgical resection and/or excisional biopsy procedure. Subject is using a pre-existing feeding tube for nutritional support at study entry.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cobiprostone 30 mcg four times daily<br>Cobiprostone oral spray, four times daily, in addition to standard care radiation and chemotherapy | Drug: Cobiprostone<br>* Cobiprostone 30 mcg oral spray<br>* Other names: SPI-8811;Drug: Standard Care - Chemotherapy<br>* Chemotherapy, as given with radiation as standard care for patients with head and neck cancer.<br>* Other names: Chemotherapy;Radiation: Standard Care - Radiation<br>* Radiation, as given with chemotherapy as standard care for patients with head and neck cancer.<br>* Other names: Radiation;|
| Placebo Comparator: Placebo 0 mcg four times daily<br>Matching placebo oral spray, four times daily, in addition to standard care radiation and chemotherapy | Drug: Placebo<br>* Matching placebo oral spray<br>* Other names: Placebo comparator;Drug: Standard Care - Chemotherapy<br>* Chemotherapy, as given with radiation as standard care for patients with head and neck cancer.<br>* Other names: Chemotherapy;Radiation: Standard Care - Radiation<br>* Radiation, as given with chemotherapy as standard care for patients with head and neck cancer.<br>* Other names: Radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a diagnosis of severe oral mucositis during the course of receiving up to 50 Gray (Gy) cumulative radiation dose administration with concurrent chemotherapy |  | 50 Gray (Gy), up to 12 weeks | 
| Overall mean Area Under the Curve (AUC) of oral mucositis severity over time |  | 50 Gray (Gy), up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-onset of severe [World Health Organization (WHO) grade 3 or 4] oral mucositis following initiation of RT/CT |  | 50 Gray (Gy), up to 12 weeks | 
| Duration of severe (World Health Organization [WHO] grade 3 or 4) oral mucositis |  | 50 Gray (Gy), up to 12 weeks | 
| Weekly Quality of Life assessment [MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN)] |  | 50 Gray (Gy), up to 12 weeks | 
| Mean cumulative radiation dose at time of severe (WHO grade 3 or 4) oral mucositis onset |  | 50 Gray (Gy), up to 12 weeks |