Clinical trial NCT00503776: Chemo/XRT +/- Amifostine to Assess Outcomes Related to Xerostomia, Mucositis, & Dysphagia
Official title: Randomized Pilot Trial of Chemoradiation Plus or Minus Amifostine to Assess Potential Nutritional, Inflammatory and Physical Outcomes Related to Xerostomia, Mucositis and Dysphagia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Dysphagia
Head and Neck Cancer
Mucositis
Xerostomia
Keywords: xerostomia
mucositis
dysphagia
radiation toxicity
chemotherapeutic agent toxicity
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage III verrucous carcinoma of the oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV verrucous carcinoma of the oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent verrucous carcinoma of the oral cavity
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
salivary gland squamous cell carcinoma
stage III salivary gland cancer
stage IV salivary gland cancer
recurrent salivary gland cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-07-19
Enrollment: 41
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Amifostine may decrease the side effects caused by chemotherapy and radiation therapy. It is not yet known whether chemotherapy and radiation therapy are more effective with or without amifostine in treating head and neck cancer.

PURPOSE: This randomized phase II trial is studying amifostine to see how well it works compared with standard care in reducing side effects in patients undergoing chemotherapy and radiation therapy for stage III or stage IV head and neck cancer.

Detailed description: OBJECTIVES:

Primary

* To compare the incidence and severity of acute and chronic swallowing dysfunction in stage III or IV head and neck cancer patients receiving concurrent chemoradiation with or without amifostine

Secondary

* To assess the relative incidence and severity of acute and chronic xerostomia in stage III or IV head and neck cancer patients receiving chemoradiation with or without amifostine.
* To assess the relative incidence and severity of mucositis and mucositis-related inflammation in stage III or IV head and neck cancer patients receiving chemoradiation with or without amifostine.
* To assess the effects of dysphagia, xerostomia, and mucositis-related inflammation on nutritional, physical, and functional status

OUTLINE: Patients undergo intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy comprising carboplatin and paclitaxel weekly.

Patients are randomized to 1 of 2 treatment arms.

* Arm I (standard of care): Patients are further divided into 1A or 1B.

  * Arm IA: Standard of care plus standardized nutrition therapy (SNT)
  * Arm IB: Standard of care plus standardized nutrition therapy plus low weight resistance training (LWRT).
* Arm II (amifostine): Patients are further divided into 2A or 2B.

  * Arm IIA: Amifostine 500mg diluted in 2.9 ml injected 30-60 minutes prior to each radiation dose plus standardized nutrition therapy
  * Arm IIB: Amifostine 500mg diluted in 2.9 ml injected 30-60 minutes prior to each radiation dose plus standardized nutrition therapy plus low weight resistance training

In all arms, patients undergo swallowing function, dietary, body composition, muscle, and physical and functional performance measurements at baseline and at 1, 3, and 6 months post-therapy. Quality of life, salivary production, fatigue, and symptoms (including swallowing/eating foods, appetite, weight loss/nutrition, pain, and speech/communication) are assessed at baseline and at 1, 3, and 6 months post-therapy. Anthropometric measurements are also performed at the above time points and at mid-therapy.

Blood samples and buccal rinses are collected at baseline and at 1, 3, and 6 months post-therapy for biomarker studies and for proteomic and genomic analysis by liquid chromatography and tandem mass spectrometry.

After completion of study treatment, patients are followed at 1, 3, and 6 months.

Eligibility criteria: Inclusion Criteria

* Age greater than 21
* Biopsy proven stage 3 or 4 squamous cell carcinoma of the larynx, pharynx, oral cavity or salivary glands
* No prior history of active cancer within three years other than non-melanoma skin cancer, early stage prostate or early stage cervical cancer
* controlled co-morbid disease
* ECOG PS of 0-3
* Plan for definitive or post-operative CCR within 4 weeks
* Written informed consent
* Working telephone
* May have received prior induction chemotherapy
* Agree to use only study supplied liquid nutrition supplements or dietary supplements, for per os or feeding tube intake

Exclusion Criteria

* Diagnosed HIV or AIDS
* History of ETOH or drug abuse within 3 months
* Pregnant or lactating
* On steroid medication or prescribed NSAIDs
* Consuming specialty nutrition supplements containing additional amounts of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)
* On orexigenic (appetite stimulant) medication.
* Uncontrolled comorbid disease defined as: a) severe cardiac disease Class III or greater; b) blood pressure \> 160/95; c) uncontrolled pain
* Does not have working telephone.

Primary outcomes:
measure: Number of Patients With Each Degree of Swallowing Dysfunction
timeFrame: 6 months after concurrent chemotherapy and radiation
Secondary outcomes:
measure: Stimulated and Unstimulated Salivary Production
timeFrame: 6 months after concurrent chemotherapy and radiation
measure: Number of Patients With Oral Mucositis by Grade
timeFrame: 6 months after concurrent chemotherapy and radiation
measure: Changes in the Amount and Texture of Food Consumed
timeFrame: at baseline, at 1 month, 3 months and 6 months post-chemoradiation
measure: Changes in the Frequency and Types of Dietary Intakes
timeFrame: at baseline, at 1 month, 3 months and 6 months post-chemoradiation
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Barbara A. Murphy, MD
role: STUDY_CHAIR
References: