Chemo/XRT +/- Amifostine to Assess Outcomes Related to Xerostomia, Mucositis, & Dysphagia

Vanderbilt University Medical Center

Status and phase: Terminated; Phase 2

Conditions: Xerostomia; Dysphagia; Mucositis; Head and Neck Cancer

Treatments: Drug: amifostine trihydrate; Procedure: therapeutic dietary intervention; Behavioral: exercise intervention

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00503776

VICC HN 0554

VU-VICC-HN-0554

VU-VICC-IRB-051068

Details and patient eligibility

About

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.

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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41 participants in 4 patient groups

Arm IA

Active Comparator group

Description:

Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.

Treatment:

Procedure: therapeutic dietary intervention

Arm IB

Active Comparator group

Description:

Patients undergo SNT and low weight resistance training (LWRT).

Treatment:

Behavioral: exercise intervention

Procedure: therapeutic dietary intervention

Arm IIA

Experimental group

Description:

Patients receive amifostine subcutaneously (SC) 30-60 minutes prior to each dose of intensity-modulated radiotherapy (IMRT). Patients also undergo SNT as in arm IA.

Treatment:

Drug: amifostine trihydrate

Procedure: therapeutic dietary intervention

Arm IIB

Experimental group

Description:

Patients receive amifostine SC 30-60 minutes prior to each dose of IMRT. Patients also undergo SNT and LWRT as in arm IB.

Treatment:

Drug: amifostine trihydrate

Behavioral: exercise intervention

Procedure: therapeutic dietary intervention