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

This study has been terminated.
(funding became unavailable)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Barbara Murphy, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00503776
First received: July 17, 2007
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Dysphagia
Head and Neck Cancer
Mucositis
Xerostomia
Behavioral: exercise intervention
Drug: amifostine trihydrate
Procedure: therapeutic dietary intervention
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Number of Patients With Each Degree of Swallowing Dysfunction [ Time Frame: 6 months after concurrent chemotherapy and radiation ] [ Designated as safety issue: No ]
    Grade of swallowing dysfunction as measured by the modified barium swallow score: grade 1, normal; grade 2, within functional limits; grade 3, mild impairment; grade 4, mild to moderate impairment; grade 5, moderate impairment; grade 6, moderate to severe impairment; grade 7, severe impairment


Secondary Outcome Measures:
  • Stimulated and Unstimulated Salivary Production [ Time Frame: 6 months after concurrent chemotherapy and radiation ] [ Designated as safety issue: No ]
    Unstimulated and stimulated salivary production, measured in mL/minute. Unstimulated salivary production is determined by expectoration of passively accumulated secretions accumulated in three 2-minute periods. Stimulated salivary production is determined by chewing paraffin wax with expectoration of passively accumulated secretions accumulated in three 2-minute periods.

  • Number of Patients With Oral Mucositis by Grade [ Time Frame: 6 months after concurrent chemotherapy and radiation ] [ Designated as safety issue: Yes ]
    Measured by Common Toxicity Criteria (CTC) v. 3.00 = no mucositis (minimum score), 1 = mild mucositis, 2 = moderate mucositis, 3 = severe mucositis, 4 = life-threatening, disabling mucositis, 5 = death (worst score).

  • Changes in the Amount and Texture of Food Consumed [ Time Frame: at baseline, at 1 month, 3 months and 6 months post-chemoradiation ] [ Designated as safety issue: No ]
    Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24-hour dietary recalls.

  • Changes in the Frequency and Types of Dietary Intakes [ Time Frame: at baseline, at 1 month, 3 months and 6 months post-chemoradiation ] [ Designated as safety issue: No ]
    Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24 hour dietary recalls.


Enrollment: 42
Study Start Date: January 2006
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm IA
Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.
Procedure: therapeutic dietary intervention
Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.
Other Name: therapeutic dietary intervention
Active Comparator: Arm IB
Patients undergo SNT and low weight resistance training (LWRT).
Behavioral: exercise intervention
Patients undergo low weight resistance training.
Other Name: exercise intervention
Procedure: therapeutic dietary intervention
Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.
Other Name: therapeutic dietary intervention
Experimental: Arm IIA
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.
Drug: amifostine trihydrate
Given subcutaneously
Other Name: Ethyol
Procedure: therapeutic dietary intervention
Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.
Other Name: therapeutic dietary intervention
Experimental: Arm IIB
Patients receive amifostine SC 30-60 minutes prior to each dose of IMRT. Patients also undergo SNT and LWRT as in arm IB.
Behavioral: exercise intervention
Patients undergo low weight resistance training.
Other Name: exercise intervention
Drug: amifostine trihydrate
Given subcutaneously
Other Name: Ethyol
Procedure: therapeutic dietary intervention
Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.
Other Name: therapeutic dietary intervention

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00503776

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Study Chair: Barbara A. Murphy, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Barbara Murphy, MD, Professor of Medicine; Director, Cancer Supportive Care Program; Director, Head and Neck Research Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00503776     History of Changes
Other Study ID Numbers: VICC HN 0554, VU-VICC-HN-0554, VU-VICC-IRB-051068
Study First Received: July 17, 2007
Results First Received: November 3, 2011
Last Updated: October 23, 2012
Health Authority: United States: Federal Government

Keywords provided by Vanderbilt-Ingram Cancer Center:
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

Additional relevant MeSH terms:
Deglutition Disorders
Head and Neck Neoplasms
Xerostomia
Mucositis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Pharyngeal Diseases
Otorhinolaryngologic Diseases
Neoplasms by Site
Neoplasms
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Gastroenteritis
Amifostine
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014