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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00068237
• Other study ID #: RTOG-0244
• Secondary ID: CDR0000287213
• Status: Completed
• Phase: Phase 2
• Start date: August 2003
• Est. completion date: December 2016

Study information

• Verified date: January 2019
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2016
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Radiation Injuries
• Radiation Toxicity
• Xerostomia

Intervention

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.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 Radia — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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%.	At the time of the submandibular salivary gland transfer
Secondary	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).	From start of treatment to 90 days
Secondary	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.	Pre-surgery, post-surgery (4-6 weeks), post radiation therapy (10-13 weeks)
Secondary	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.	Baseline and one year
Secondary	Percentage of Patients Experiencing Facial Edema Following Surgery	Facial edema was noted as present or absent following surgery.	From surgery to 30 days after surgery
Secondary	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.	From start of radiation therapy to 90 days
Secondary	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.	From 91 days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 5.6 years.
Secondary	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.	From registration to two years
Secondary	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.	From registration to two years