search
Back to results

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

Primary Purpose

Head and Neck Cancer, Radiation Toxicity, Xerostomia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
salivary gland transfer
Post-operative radiation therapy
Sponsored by
Radiation Therapy Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Head and Neck Cancer focused on measuring xerostomia, radiation toxicity, 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Florida Shands Cancer Center
  • University of Miami Sylvester Comprehensive Cancer Center - Miami
  • Cancer Institute at St. John's Hospital
  • Josephine Ford Cancer Center at Henry Ford Hospital
  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
  • Hollings Cancer Center at Medical University of South Carolina
  • M. D. Anderson Cancer Center at University of Texas
  • Medical College of Wisconsin Cancer Center
  • Veterans Affairs Medical Center - Milwaukee
  • Cross Cancer Institute at University of Alberta
  • Doctor H. Bliss Murphy Cancer Centre
  • Centre Hospitalier Universitaire de Quebec

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Surgery + Transfer + Radiation

Arm Description

Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.

Outcomes

Primary Outcome Measures

Number of Patients Scored as Having the Surgical Technique of Submandibular Salivary Gland Transfer Performed "Per Protocol"
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

Percentage of Patients With Acute Xerostomia
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).
Percentage of Patients With Normal Functioning Transferred Submandibular Gland
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.
Change From Baseline to One Year in Total Score on the Modified University of Washington Head and Neck Symptom Questionnaire
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.
Percentage of Patients Experiencing Facial Edema Following Surgery
Facial edema was noted as present or absent following surgery.
Percentage of Patients Experiencing Acute Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy or Chemotherapy
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.
Percentage of Patients Experiencing Late Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy
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.
Disease-free Survival Rate at 2 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.
Overall Survival Rate at 2 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.

Full Information

First Posted
September 10, 2003
Last Updated
February 1, 2019
Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00068237
Brief Title
Salivary Gland Surgery Before Radiation Therapy in Preventing Radiation-Caused Xerostomia in Patients With Head and Neck Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
August 2003 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer, Radiation Toxicity, Xerostomia
Keywords
xerostomia, radiation toxicity, 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

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Surgery + Transfer + Radiation
Arm Type
Experimental
Arm Description
Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Intervention Type
Procedure
Intervention Name(s)
salivary gland transfer
Intervention Description
Seikaly and Jha method of submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes on Day 1
Intervention Type
Radiation
Intervention Name(s)
Post-operative radiation therapy
Intervention Description
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 Measure Information:
Title
Number of Patients Scored as Having the Surgical Technique of Submandibular Salivary Gland Transfer Performed "Per Protocol"
Description
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%.
Time Frame
At the time of the submandibular salivary gland transfer
Secondary Outcome Measure Information:
Title
Percentage of Patients With Acute Xerostomia
Description
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).
Time Frame
From start of treatment to 90 days
Title
Percentage of Patients With Normal Functioning Transferred Submandibular Gland
Description
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.
Time Frame
Pre-surgery, post-surgery (4-6 weeks), post radiation therapy (10-13 weeks)
Title
Change From Baseline to One Year in Total Score on the Modified University of Washington Head and Neck Symptom Questionnaire
Description
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.
Time Frame
Baseline and one year
Title
Percentage of Patients Experiencing Facial Edema Following Surgery
Description
Facial edema was noted as present or absent following surgery.
Time Frame
From surgery to 30 days after surgery
Title
Percentage of Patients Experiencing Acute Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy or Chemotherapy
Description
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.
Time Frame
From start of radiation therapy to 90 days
Title
Percentage of Patients Experiencing Late Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy
Description
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.
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.
Title
Disease-free Survival Rate at 2 Years
Description
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.
Time Frame
From registration to two years
Title
Overall Survival Rate at 2 Years
Description
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.
Time Frame
From registration to two years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naresh Jha, MBBS
Organizational Affiliation
Cross Cancer Institute at University of Alberta
Official's Role
Study Chair
Facility Information:
Facility Name
University of Florida Shands Cancer Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0232
Country
United States
Facility Name
University of Miami Sylvester Comprehensive Cancer Center - Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Cancer Institute at St. John's Hospital
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Josephine Ford Cancer Center at Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1240
Country
United States
Facility Name
Hollings Cancer Center at Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
M. D. Anderson Cancer Center at University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Medical College of Wisconsin Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Veterans Affairs Medical Center - Milwaukee
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53295
Country
United States
Facility Name
Cross Cancer Institute at University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Doctor H. Bliss Murphy Cancer Centre
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
Centre Hospitalier Universitaire de Quebec
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
22541957
Citation
Jha N, Harris J, Seikaly H, Jacobs JR, McEwan AJ, Robbins KT, Grecula J, Sharma AK, Ang KK. A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244). Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):437-42. doi: 10.1016/j.ijrobp.2012.02.034. Epub 2012 Apr 27.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs