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Salivary Gland Surgery Before Radiation Therapy in Preventing Radiation-Caused Xerostomia in Patients With Head and Neck Cancer

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ClinicalTrials.gov Identifier: NCT00068237
Recruitment Status : Completed
First Posted : September 11, 2003
Results First Posted : January 31, 2014
Last Update Posted : February 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Brief Summary:

RATIONALE: Moving a salivary gland out of the area that will undergo radiation therapy may protect the gland from side effects of radiation therapy and may prevent xerostomia (dry mouth).

PURPOSE: Phase II trial to study the effectiveness of salivary gland surgery in preventing xerostomia in patients who are undergoing radiation therapy for head and neck cancer.


Condition or disease Intervention/treatment Phase
Head and Neck Cancer Radiation Toxicity Xerostomia Procedure: salivary gland transfer Radiation: Post-operative radiation therapy Phase 2

Detailed Description:

OBJECTIVES:

  • Determine the reproducibility of the surgical technique of submandibular salivary gland transfer in patients with head and neck cancer.
  • Determine the rate and severity of radiation-induced xerostomia after this surgery in these patients.
  • Determine the pattern of recurrence, disease-free survival, and overall survival of patients treated with this surgery followed by radiotherapy.
  • Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients undergo surgical transfer of the submandibular salivary gland to the submental space.

Within 4-6 weeks after surgery, patients undergo radiotherapy once daily, 5 days a week for 5 ½ to 7 weeks in the absence of disease progression or unacceptable toxicity.

Salivary scans are performed before surgery, at 2-3 weeks after surgery, and then at 6 months from the start of radiotherapy.

Quality of life is assessed at baseline and at 3, 6, and 12 months from the start of radiotherapy.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years and then annually.

PROJECTED ACCRUAL: A total of 11-48 patients will be accrued for this study within 1.6 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Phase II Study Of Submandibular Salivary Gland Transfer To The Submental Space Prior To Start Of Radiation Treatment For Prevention Of Radiation-Induced Xerostomia In Head And Neck Cancer Patients
Study Start Date : August 2003
Actual Primary Completion Date : January 2008
Actual Study Completion Date : December 2016


Arm Intervention/treatment
Experimental: Surgery + Transfer + Radiation
Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Procedure: salivary gland transfer
Seikaly and Jha method of submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes on Day 1

Radiation: Post-operative radiation therapy
Dose ranging from 54-70 Gy over 5.5-7 weeks, at 2.0 Gy/fraction. Starts within 4-6 weeks of surgery.




Primary Outcome Measures :
  1. Number of Patients Scored as Having the Surgical Technique of Submandibular Salivary Gland Transfer Performed "Per Protocol" [ Time Frame: At the time of the submandibular salivary gland transfer ]
    Surgery will be scored as "per protocol prescription" if scored as such by both central reviewers- the Study Chair and the Radiation Therapy Oncology Group Head and Neck Committee Surgical Chair. If 21 or more of 43 subjects are scored as having surgery "per protocol prescription", then the technique will be considered reproducible with 80% power and 5% type I error using Simon's two stage design with unacceptable/acceptable rates set at 60%/80%.


Secondary Outcome Measures :
  1. Percentage of Patients With Acute Xerostomia [ Time Frame: From start of treatment to 90 days ]
    The proportion of patients who experience grade 2 or higher xerostomia or start amifostine and/or pilocarpine within 90 days of the start of radiation therapy. A proportion less than or equal to 51% would be considered acceptable based on the results of the U.S. Bioscience phase III amifostine trial (this trial preceded FDAAA requirements).

  2. Percentage of Patients With Normal Functioning Transferred Submandibular Gland [ Time Frame: Pre-surgery, post-surgery (4-6 weeks), post radiation therapy (10-13 weeks) ]
    Salivary gland functioning classified as "Non-functioning", "Minimal function", "Well-functioning but some impairment", "Normal functioning", or "Other" is determined by central review of scintigraphy scans using sodium pertechnetate (Na-99mTcO4-) with a sialagogue (lemon juice) administered halfway through the study to determine if secretory function is maintained.

  3. Change From Baseline to One Year in Total Score on the Modified University of Washington Head and Neck Symptom Questionnaire [ Time Frame: Baseline and one year ]
    The University of Washington Head and Neck Symptom Questionnaire, also referred to as the University of Washington Health Related Quality of Life tool (UW-QOL) was modified for use by the Radiation Therapy Oncology Group (RTOG). The resulting UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The UW-QOL-RTOG modification consists of 15 items with response options ranging from 10-50, in multiples of 10. That is, the lowest symptom burden is rated as 10, while the highest symptom burden is rated as 50. The individual item scores are averaged to obtain the final score which also ranges from 10 to 50. This scoring results in a lower score indicating greater HR-QOL; and conversely, higher scores indicating lower health-related quality of life (HR-QOL). Change = baseline score - one year score, such that a positive change score indicates improvement.

  4. Percentage of Patients Experiencing Facial Edema Following Surgery [ Time Frame: From surgery to 30 days after surgery ]
    Facial edema was noted as present or absent following surgery.

  5. Percentage of Patients Experiencing Acute Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy or Chemotherapy [ Time Frame: From start of radiation therapy to 90 days ]
    Adverse events are graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) v2.0. Grade refers to the severity of the toxicity by assigning Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. "Acute" refers to toxicities occurring less than or equal to 90 days from the start of radiation therapy.

  6. Percentage of Patients Experiencing Late Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy [ Time Frame: From 91 days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 5.6 years. ]
    Adverse events are graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) v2.0. Grade refers to the severity of the toxicity by assigning Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. "Late" refers to toxicities occurring at least 91 days from the start of radiation therapy.

  7. Disease-free Survival Rate at 2 Years [ Time Frame: From registration to two years ]
    Failure was defined as local, regional, or distant recurrence/progression, second primary tumor, or death due to any cause. Disease-free survival time is defined as time from registration to the the date of failure or last known follow-up (censored). Disease-free survival rate is estimated using the kaplan-meier method.

  8. Overall Survival Rate at 2 Years [ Time Frame: From registration to two years ]
    Failure was defined as death due to any cause. Survival time is defined as time from registration to the the date of failure or last known follow-up (censored). Survival rate is estimated using the kaplan-meier method.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Histologically confirmed, previously untreated squamous cell carcinoma of the oropharynx, hypopharynx, or larynx
    • Head and neck cancer of unknown primary with unilateral metastases to the neck nodes
  • No N3 disease
  • No carcinoma of the oral cavity or nasopharynx
  • No bilateral neck node involvement
  • No suspicious neck node on the contralateral neck or the side chosen for salivary gland transfer by CT scan or MRI
  • No pre-epiglottic space involvement
  • No involvement of level 1 nodes on either side of the neck
  • No salivary gland malignancy
  • No recurrent disease

PATIENT CHARACTERISTICS:

Age

  • At least 18 years old

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Hemoglobin at least 10 g/dL

Hepatic

  • Not specified

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No salivary gland disease (e.g., Sjögren's syndrome)
  • No other malignancy within the past 3 years except basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • More than 3 years since prior chemotherapy
  • No prior or concurrent neoadjuvant chemotherapy
  • Concurrent adjuvant chemoradiotherapy (in addition to study radiotherapy) allowed

Endocrine therapy

  • Not specified

Radiotherapy

  • See Chemotherapy
  • No prior radiotherapy to the head and neck
  • No concurrent intensity-modulated radiotherapy

Surgery

  • Not specified

Other

  • No concurrent cholinergic drugs
  • No concurrent anti-cholinergic drugs
  • No concurrent tricyclic drugs
  • No concurrent prophylactic amifostine or pilocarpine during and for at least 3 months after completion of study radiotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00068237


Locations
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United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
United States, Illinois
Cancer Institute at St. John's Hospital
Springfield, Illinois, United States, 62702
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Veterans Affairs Medical Center - Milwaukee
Milwaukee, Wisconsin, United States, 53295
Canada, Alberta
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Newfoundland and Labrador
Doctor H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Quebec
Centre Hospitalier Universitaire de Quebec
Quebec City, Quebec, Canada, G1R 2J6
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: Naresh Jha, MBBS Cross Cancer Institute at University of Alberta

Publications of Results:
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Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00068237     History of Changes
Other Study ID Numbers: RTOG-0244
CDR0000287213
First Posted: September 11, 2003    Key Record Dates
Results First Posted: January 31, 2014
Last Update Posted: February 5, 2019
Last Verified: January 2019

Keywords provided by Radiation Therapy Oncology Group:
xerostomia
stage II squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the oropharynx
stage I squamous cell carcinoma of the hypopharynx
stage II squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
untreated metastatic squamous neck cancer with occult primary
stage IV squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the oropharynx
radiation toxicity

Additional relevant MeSH terms:
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Head and Neck Neoplasms
Xerostomia
Radiation Injuries
Neoplasms by Site
Neoplasms
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Wounds and Injuries