Head and Neck Cancer, Xerostomia
Conditions
Keywords
hypopharyngeal cancer, laryngeal cancer, lip and oral cavity cancer, nasopharyngeal cancer, paranasal sinus and nasal cavity cancer, oropharyngeal cancer, salivary gland cancer, metastatic squamous neck cancer with occult primary, xerostomia, tongue cancer
Brief summary
RATIONALE: Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) and pilocarpine may help to relieve chronic xerostomia (dry mouth). It is not yet known which remedy is more effective in treating chronic dry mouth caused by radiation therapy in patients with head and neck cancer. PURPOSE: This randomized phase II/III trial is studying ALTENS to see how well it works compared with pilocarpine in treating chronic dry mouth caused by radiation therapy in patients with head and neck cancer.
Detailed description
OBJECTIVES: Primary * Determine the feasibility of successfully delivering acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) using the Codetron™ unit in a cooperative group setting in head and neck cancer patients with early radiotherapy-induced xerostomia. (phase II) * Compare the efficacy of ALTENS treatment vs pilocarpine hydrochloride in these patients in reducing overall xerostomia burden, as measured by the University of Michigan 15-item Xerostomia-Related Quality of Life Scale (XeQOLS) at 9 months after randomization. (phase III) Secondary * Evaluate the effect of ALTENS treatment on overall xerostomia burden at 6 months after study entry in these patients. (phase II) * Compare the efficacy of these treatments in these patients in reducing overall xerostomia burden at 4, 6, and 15 months after randomization. (phase III) * Compare the efficacy of these treatments in these patients in reducing symptom burden, as measured by the four domains of the XeQOLS (i.e., physical functioning, social functioning, personal/psychological functioning, and pain/discomfort) at 4, 6, 9, and 15 months after randomization. (phase III) * Compare the efficacy of these treatments in these patients in increasing stimulated (i.e., citric acid primed) whole salivary production (WSP), as measured by sialometry, at 4, 6, 9, and 15 months after randomization. (phase III) * Compare the efficacy of these treatments in these patients in increasing unstimulated (i.e., basal primed) WSP, as measured by sialometry at 4, 6, 9, and 15 months after randomization. (phase III) * Compare adverse events associated with these treatments in these patients. (phase III) OUTLINE: This is a phase II followed by a phase III multicenter study. * Phase II:Patients undergo placement of surface electrodes at the following acupuncture points: large intestine, spleen, stomach, and conception vessel. Patients then undergo acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) to each of these points using the Codetron™ unit for 20 minutes twice weekly for 12 weeks. No further treatment is given after 12 weeks. * Phase III:Patients are stratified according to prior use of pilocarpine (no vs yes) and length of time from completion of chemotherapy and/or radiotherapy (3-6 months vs 6-12 months vs \> 12 months). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral pilocarpine three times daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity. * Arm II: Patients undergo ALTENS treatment using the Codetron™ unit twice weekly for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo quality of life (QOL) assessment at baseline and at 6 months after registration in phase II. In phase III patients complete assessments for basal and stimulated whole salivary production, xerostomia burden, and QOL at baseline and at 4, 6, 9, and 15 months after study entry. After completion of study therapy, patients are followed at 3 months. PROJECTED ACCRUAL: A total of 45 patients will be accrued to the phase II portion and 144 patients to the phase III portion of this study.
Interventions
DRUGPilocarpine
5mg by mouth 3 times a day for 12 weeks
PROCEDUREALTENS
Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit
Sponsors
National Cancer Institute (NCI)
NRG Oncology
Radiation Therapy Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
One arm Phase II followed by a two-arm Phase III
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of head and neck cancer * No clinical evidence of disease recurrence by ear, nose, and throat exam with a nasopharyngeal scope, if indicated, 8 weeks prior to registration * Completed radiotherapy (i.e., standard or intensity-modulated radiotherapy) with or without chemotherapy ≥ 3 months and up to 2 years prior to study entry * Grade 1-2 radiotherapy-induced xerostomia according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v.3.0 and the dry mouth/salivary gland xerostomia scale * Must have evidence of residual salivary function with unstimulated (basal) whole salivary production ≥ 0.1 ml/min after having refrained from eating or drinking oral fluid for 2 hours * No patients with normal saliva production (i.e., no salivary gland changes or no xerostomia) * No history of serious adverse events after prior treatment with and discontinuation of pilocarpine * No chronic lymphocytic leukemia PATIENT CHARACTERISTICS: * See Disease Characteristics * Zubrod performance status of 0-2 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other invasive malignancy except non-melanomatous skin cancer or cancer from which the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix) * No concurrent contraindications to pilocarpine (e.g., uncontrolled asthma, miosis, or hypersensitivity) * No severe, active co-morbidity, including any of the following: * Unstable cardiac disease or requirement for a pacemaker in-situ * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months * Transmural myocardial infarction within the past 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * No Sjögren syndrome PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 2 weeks since prior pilocarpine or cevimeline and no concurrent use for ophthalmic or non-ophthalmic indications * No concurrent regular medications that induce xerostomia (e.g., tricyclic antidepressants, antihistamines with anticholinergic effects, or narcotics) * No concurrent oral stimulating agents or salivary gland medical stimulants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Treatment Compliance (Number of Compliant Patients) | Randomization to 12 weeks | Patients completing at least 19 out of 24 ALTENS therapy sessions were categorized as compliant. Fleming's two-stage was used, assuming a successful target compliance rate of 80%, statistical power of 0.87, and a type I error rate of 0.13. If fewer than 9 of the first 13 patients were compliant, then treatment delivery will be deemed not feasible. If there were between 9-12 compliant patients, the second stage analysis would be required to determine feasibility of treatment delivery. If all 13 patients are compliant, treatment delivery will immediately be deemed feasible. The second stage analysis required at least 31 compliant out of 39 overall patients for the treatment delivery to be deemed feasible. |
| Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months | Baseline (randomization) and 9 months | Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | Baseline, 4, 6, 9 and 15 months from randomization | Symptom burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning. The domain score is the average of all responses on a given domain and can range from 0 to 4, with higher scores indicating increased symptom burden. Change in symptom burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the symptom burden. |
| Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | Baseline, 4, 6, 9 and 15 months from randomization | Stimulated (citric acid primed) whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. Stimulation is elicited by asking patients to rinse 5 ml of 2% citric acid solution in the mouth for 15 seconds and then completely expectorating the citric acid. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected. |
| Phase II: Pecentage of Patients With Beneficial Treatment Response | Pre-treatment and 6 months from registration | This secondary objective was to evaluate the effect of ALTENS treatment on overall radiation-induced xerostomia burden by looking at treatment response. Treatment response was determined by a reduction of at least 20% from baseline to 6 months in the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4. Higher scores indicate increased xerostomia burden. This scale has high reproducibility and sensitivity. For the first and second stage analyses, 4 and 10 patients, respectively, must respond to treatment in order to proceed to the phase III component. |
| Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III | Baseline and 9 months from randomization. | The UWHNSS includes ten categories-pain, disfigurement, activity, recreation/entertainment, employment, eating, saliva, taste, speech, mucus/phlegm. Patient scores on the UWHNSS range from 0 to 100 with higher scores indicating declining quality of life. Change in total score was calculated by subtracting baseline from follow-up , thus a positive change score indicates a worsening while a negative change score indicates an improvement. |
| Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | Pre-treatment to 4, 6, 9 and 15 months from randomization | Basal whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected. |
| Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) | Baseline, 4, 6, and 15 months from randomization | Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ALTENS: Phase II Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit | 47 |
| Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks | 73 |
| ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit | 73 |
| Total | 193 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Incomplete treatment | 3 | 0 | 0 |
| Overall Study | Missing baseline form | 0 | 5 | 5 |
| Overall Study | Missing data | 0 | 11 | 9 |
| Overall Study | Protocol Violation | 1 | 0 | 2 |
| Overall Study | Treatment completed outside of timeframe | 0 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 11 | 4 |
Baseline characteristics
| Characteristic | ALTENS: Phase II | Pilocarpine: Phase III | ALTENS: Phase III | Total |
|---|---|---|---|---|
| Age, Continuous | 60 years | 59 years | 58 years | 58 years |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 11 Participants | 28 Participants |
| Sex: Female, Male Male | 40 Participants | 63 Participants | 62 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 47 | 51 / 73 | 27 / 72 |
| serious Total, serious adverse events | 1 / 47 | 0 / 73 | 1 / 72 |
Outcome results
Primary
Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months
Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden.
Time frame: Baseline (randomization) and 9 months
Population: Eligible randomized patients with both baseline and 9 month XeQOLS scores
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ALTENS: Phase II | Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months | -0.27 units on a scale |
| ALTENS: Phase III | Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months | -0.53 units on a scale |
Comparison: An effect size of 0.50 was chosen for sample size calculation. On the basis of a 2-sided t test with alpha= 0.05 and 1 interim analysis, 130 patients were required for 80% statistical power. Adjustment by 10% for loss to follow-up and retrospective ineligibility of recruited study participants yielded a sample size of 144 patients. Actual power given only 96 patients was 68.6%p-value: 0.45Wilcoxon (Mann-Whitney)
Primary
Phase II: Treatment Compliance (Number of Compliant Patients)
Patients completing at least 19 out of 24 ALTENS therapy sessions were categorized as compliant. Fleming's two-stage was used, assuming a successful target compliance rate of 80%, statistical power of 0.87, and a type I error rate of 0.13. If fewer than 9 of the first 13 patients were compliant, then treatment delivery will be deemed not feasible. If there were between 9-12 compliant patients, the second stage analysis would be required to determine feasibility of treatment delivery. If all 13 patients are compliant, treatment delivery will immediately be deemed feasible. The second stage analysis required at least 31 compliant out of 39 overall patients for the treatment delivery to be deemed feasible.
Time frame: Randomization to 12 weeks
Population: Eligible patients starting protocol treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALTENS: Phase II | Phase II: Treatment Compliance (Number of Compliant Patients) | First Stage | 12 Participants |
| ALTENS: Phase II | Phase II: Treatment Compliance (Number of Compliant Patients) | Second Stage (Overall) | 44 Participants |
Secondary
Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)
Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden.
Time frame: Baseline, 4, 6, and 15 months from randomization
Population: Eligible patients with both baseline and respective follow-up (4,6,15 months) XeQOLS scores.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ALTENS: Phase II | Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) | 6 months | -0.33 units on a scale |
| ALTENS: Phase II | Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) | 15 months | -0.47 units on a scale |
| ALTENS: Phase II | Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) | 4 months | -0.27 units on a scale |
| ALTENS: Phase III | Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) | 4 months | -0.47 units on a scale |
| ALTENS: Phase III | Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) | 6 months | -0.4 units on a scale |
| ALTENS: Phase III | Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) | 15 months | -0.6 units on a scale |
p-value: 0.11Wilcoxon (Mann-Whitney)
p-value: 0.31Wilcoxon (Mann-Whitney)
p-value: 0.21Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Stimulated (citric acid primed) whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. Stimulation is elicited by asking patients to rinse 5 ml of 2% citric acid solution in the mouth for 15 seconds and then completely expectorating the citric acid. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected.
Time frame: Baseline, 4, 6, 9 and 15 months from randomization
Population: Eligible patients with both baseline and respective follow-up (4,6, 9,15 months) WSP measurements.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ALTENS: Phase II | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 4 months | 0.03 ml/min |
| ALTENS: Phase II | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 6 months | 0.2 ml/min |
| ALTENS: Phase II | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 9 months | 0.99 ml/min |
| ALTENS: Phase II | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 15 months | 0.3 ml/min |
| ALTENS: Phase III | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 15 months | 0.20 ml/min |
| ALTENS: Phase III | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 4 months | 0.2 ml/min |
| ALTENS: Phase III | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 9 months | 0.60 ml/min |
| ALTENS: Phase III | Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 6 months | 0.40 ml/min |
p-value: 0.97Wilcoxon (Mann-Whitney)
p-value: 0.83Wilcoxon (Mann-Whitney)
p-value: 0.28Wilcoxon (Mann-Whitney)
p-value: 0.89Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Symptom burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning. The domain score is the average of all responses on a given domain and can range from 0 to 4, with higher scores indicating increased symptom burden. Change in symptom burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the symptom burden.
Time frame: Baseline, 4, 6, 9 and 15 months from randomization
Population: Eligible patients with both baseline and respective follow-up (4,6, 9,15 months) XeQOLS scores.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Physical Functioning | -0.5 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Social Functioning | 0 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Social Functioning | -0.33 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Pain/Discomfort | -0.25 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Social Functioning | 0 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Physical Functioning | -0.5 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Pain/Discomfort | -0.25 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Personal/Psychological Functioning | -0.25 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Physical Functioning | -0.5 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Physical Functioning | -0.5 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Pain/Discomfort | -0.25 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Personal/Psychological Functioning | -0.5 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Social Functioning | -0.66 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Pain/Discomfort | -0.5 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Personal/Psychological Functioning | -0.5 units on a scale |
| ALTENS: Phase II | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Personal/Psychological Functioning | -0.25 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Social Functioning | -0.33 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Pain/Discomfort | -0.375 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Physical Functioning | -0.5 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Pain/Discomfort | -0.5 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Personal/Psychological Functioning | -0.5 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 6-month Social Functioning | -0.33 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Physical Functioning | -0.5 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Pain/Discomfort | -0.5 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Social Functioning | -0.33 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Physical Functioning | -0.75 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Pain/Discomfort | -0.5 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 15-month Personal/Psychological Functioning | -0.75 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Personal/Psychological Functioning | -0.5 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Social Functioning | -0.33 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 9-month Personal/Psychological Functioning | -0.75 units on a scale |
| ALTENS: Phase III | Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) | 4-month Physical Functioning | -0.5 units on a scale |
p-value: 0.35Wilcoxon (Mann-Whitney)
p-value: 0.78Wilcoxon (Mann-Whitney)
p-value: 0.12Wilcoxon (Mann-Whitney)
p-value: 0.28Wilcoxon (Mann-Whitney)
p-value: 0.98Wilcoxon (Mann-Whitney)
p-value: 0.28Wilcoxon (Mann-Whitney)
p-value: 0.13Wilcoxon (Mann-Whitney)
p-value: 0.58Wilcoxon (Mann-Whitney)
p-value: 0.88Wilcoxon (Mann-Whitney)
p-value: 0.09Wilcoxon (Mann-Whitney)
p-value: 0.49Wilcoxon (Mann-Whitney)
p-value: 0.45Wilcoxon (Mann-Whitney)
p-value: 0.45Wilcoxon (Mann-Whitney)
p-value: 0.3Wilcoxon (Mann-Whitney)
p-value: 0.48Wilcoxon (Mann-Whitney)
p-value: 0.68Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Basal whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected.
Time frame: Pre-treatment to 4, 6, 9 and 15 months from randomization
Population: Eligible randomized patients with both baseline and respective follow-up (4,6, 9,15 months) WSP measurements.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ALTENS: Phase II | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 4 months | 0 ml/min |
| ALTENS: Phase II | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 6 months | 0 ml/min |
| ALTENS: Phase II | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 9 months | 0.056 ml/min |
| ALTENS: Phase II | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 15 months | 0.13 ml/min |
| ALTENS: Phase III | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 15 months | 0.192 ml/min |
| ALTENS: Phase III | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 4 months | 0 ml/min |
| ALTENS: Phase III | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 9 months | 0.04 ml/min |
| ALTENS: Phase III | Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) | 6 months | 0.02 ml/min |
p-value: 0.54Wilcoxon (Mann-Whitney)
p-value: 0.99Wilcoxon (Mann-Whitney)
p-value: 0.56Wilcoxon (Mann-Whitney)
p-value: 0.58Wilcoxon (Mann-Whitney)
Secondary
Phase II: Pecentage of Patients With Beneficial Treatment Response
This secondary objective was to evaluate the effect of ALTENS treatment on overall radiation-induced xerostomia burden by looking at treatment response. Treatment response was determined by a reduction of at least 20% from baseline to 6 months in the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4. Higher scores indicate increased xerostomia burden. This scale has high reproducibility and sensitivity. For the first and second stage analyses, 4 and 10 patients, respectively, must respond to treatment in order to proceed to the phase III component.
Time frame: Pre-treatment and 6 months from registration
Population: Eligible patients who started treatment and have both baseline and 6-month XeQOLS scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALTENS: Phase II | Phase II: Pecentage of Patients With Beneficial Treatment Response | 85.7 percentage of participants |
Secondary
Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III
The UWHNSS includes ten categories-pain, disfigurement, activity, recreation/entertainment, employment, eating, saliva, taste, speech, mucus/phlegm. Patient scores on the UWHNSS range from 0 to 100 with higher scores indicating declining quality of life. Change in total score was calculated by subtracting baseline from follow-up , thus a positive change score indicates a worsening while a negative change score indicates an improvement.
Time frame: Baseline and 9 months from randomization.
Population: Eligible randomized patients with both baseline and 9-month UWHNSS total scores.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ALTENS: Phase II | Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III | -3.64 units on a scale |
| ALTENS: Phase III | Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III | -7.27 units on a scale |
p-value: 0.14t-test, 2 sided