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Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer

Primary Purpose

Stage I Papillary Thyroid Cancer, Stage II Papillary Thyroid Cancer, Stage III Papillary Thyroid Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Thyroidectomy
entral lymph node dissection (CLND)
Quality-of-life assessment
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage I Papillary Thyroid Cancer

Eligibility Criteria

21 Years - 73 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pre-operative diagnosis or suspicion of papillary thyroid cancer, usually by fine needle aspiration (FNA)
  • No pre-operative evidence of cervical lymph node metastases on neck ultrasound (randomization arms only)
  • No evidence of distant metastases
  • Ability to read and write in English

Exclusion Criteria:

  • Largest papillary thyroid carcinoma < 1 cm in size on ultrasound
  • Previous thyroid surgery
  • Concurrent active malignancy of another type
  • Inability to give informed consent or lacks decision making capacity
  • T4 tumor
  • Pre-existing vocal cord paralysis
  • Chronic neurologic condition which affects voice or swallow (for instance, multiple sclerosis or Parkinson disease)
  • Baseline laryngeal pathology that would warrant intervention that could affect voice or swallow function
  • Becomes pregnant before surgery or at any time while on study

INTRA-OPERATION EXCLUSION CRITERIA (randomization arms only)

  • Evidence of nodal involvement identified in the operating room (OR)
  • Failure to confirm diagnosis of cancer in participant

Sites / Locations

  • University of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Arm I (no CND)

Arm II (CND)

Arm III (SOC)

Arm Description

Patients undergo total thyroidectomy alone.

Patients undergo total thyroidectomy with ipsilateral prophylactic CND.

Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference

Outcomes

Primary Outcome Measures

Percentage of Participants With Transient Hypoparathyroidism, as Defined by a Day 1 Serum Parathyroid Hormone (PTH) Level of < 10 pg/ml
Rate of transient hypoparathyroidism will be assessed in terms of percentage of participants with day 1 serum PTH level of < 10 pg/ml.
Post-operative Serum Calcium (mg/dL) at Day 12
Post-operative serum calcium (mg/dL) at Day 12
Total Calcium Consumption in First 2 Weeks
Total calcium consumption in first 2 weeks (total mg). Participants were given calcium symptom logs in which to record their calcium consumption between surgery and their first preoperative follow up appointment, approximately two week.
Number of Participants With Hypocalcemia Symptoms in First 2 Weeks
Number of participants with hypocalcemia symptoms and symptom severity in first two weeks, as defined by presence of clinically significant symptoms of hypocalcemia. Clinically significant symptoms defined as 1 or more episodes of symptoms of hypocalcemia per day for multiple days, symptoms leading to calls to provider for assistance with managing and/or symptoms leading to escalation of dosage of prescribed medications to treat symptoms of hypocalcemia
Hypocalcemia Symptom Severity Scale (Range of 1-5)
Mean number of occurrences of mild (severity 1 - 2) and severe (severity 3 - 5) hypocalcemia symptoms. Participants were asked to record hypocalcemia symptoms between surgery and first postoperative follow-up at approximately two weeks in their provided calcium symptom logs and rank severity on scale of 1 (mild) to 5 (severe).
Percentage of Participants That Required Calcium and Calcitriol at Month 6
Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH <15 pg/ml)
Post-operative Serum PTH (pg/ml) at Month 6
Post-operative Serum Calcium Level at Month 6
Post-operative serum calcium (mg/dL) at Month 6

Secondary Outcome Measures

Rate of Transient and Permanent Hypocalcemia
The rate of transient and permanent hypocalcemia will be determined by assessing the following: I. Post-operative serum calcium (mg/dl) and PTH (pg/ml) at Day 12 and Month 6 II. Total calcium consumption in first 2 weeks (total gm) III. Hypocalcemia symptoms in first 2 weeks (average episodes/day) IV. Hypocalcemia symptom severity scale (range 1-5) V. Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH < 15 pg/ml Data will be analyzed using the methods described above.
Rate of Voice and Swallowing Problems
The rate of voice and swallowing problems will be determined by assessing the following: I. Phonation threshold pressure, in centimeters of water II. Dysphonia severity index (DSI) score (+5 to -5) III. Grade Roughness Breathiness Asthenia Strain (GRBAS) score (0-3) IV. Voice quality parameters as measured by Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) (0-100 on visual analog scale) V. Vocal fold vibratory and movement parameters as measured by stroboscopy assessment (1-4) VI. Glottal function index score VII. Penetration-Aspiration score as measured by videofluoroscopic swallow study (0-8) Data will be analyzed using the methods described above.
Degree to Which Quality of Life (QOL) is Compromised
The degree to which quality (QOL) is compromised will be determined by assessing the following: I. Short Form Health Survey (SF-12) Mental Composite Scale (MCS) score II. Short Form Health Survey (SF-12) Physical Composite Scale (PCS) score III. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core-30 (C30) score IV. Thyroid Cancer Specific Quality of Life (ThyCA-QOL) score V. 10-item Eating Assessment Tool (EAT-10) dysphagia inventory score VI. Voice Handicap Index (VHI) score VII. Themes and codes from interview transcripts assessed using qualitative research methods Data will be analyzed using the methods described above.
Clinical Recurrence Rates
Clinical recurrence rates will be determined by assessing the following: I. Percent of patients with a recombinant thyroid-stimulating hormone (rTSH) stimulated thyroglobulin level < 1 ng/ml one year after surgery II. Unstimulated thyroglobulin level prior to beginning week 6 radioactive iodine treatment III. Stimulated thyroglobulin at the time of week 6 radioactive iodine treatment IV. Incidence of unstimulated thyroglobulin > 1 ng/mL at 6 months V. Incidence of stimulated thyroglobulin > 2 ng/mL at 1 year VI. Incidence of biopsy-proven disease identification on neck ultrasound or iodine-131 (I-131) uptake up to 5 years post-surgery Data will be analyzed using the methods described above.
Degree to Which Accurate Quality of Life (QOL) Measures Can be Extracted From Patient Interview Narratives Using Natural Language Processing Techniques
The degree to which accurate quality of life (QOL) measures can be extracted from patient interview narratives using natural language process techniques will allow for the development of computer algorithms that convert patient narrative text into simple quality of life measures. Data will be analyzed using the methods described above.

Full Information

First Posted
May 12, 2014
Last Updated
November 24, 2020
Sponsor
University of Wisconsin, Madison
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02138214
Brief Title
Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer
Official Title
Thyroid Gland Removal With or Without Central Lymph Node Dissection in Treating Patients With Node Negative Thyroid Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
June 6, 2014 (Actual)
Primary Completion Date
October 30, 2019 (Actual)
Study Completion Date
October 26, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well thyroid gland removal with or without central lymph node dissection works in treating patients with thyroid cancer or suspected thyroid cancer that has not spread to the lymph nodes (randomized into Arms I and II). Arms I and II are compared to a standard of care (SOC) Arm III to enable comparison of quality of life among various surgical treatments. Currently, the standard treatment for thyroid cancer is total thyroidectomy, or complete removal of the thyroid. The lymph nodes in the central part of the neck may also be surgically removed, called central lymph node dissection. Prophylactic removal of the lymph nodes may increase the risk of life-threatening complications, and may reduce post-surgery quality of life. It may also prevent the cancer from returning and reduce the need for additional surgery. It is not yet known whether recurrence rates and complication levels are lower after thyroid gland removal alone or with central lymph node dissection.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the rate of transient and permanent hypocalcemia SECONDARY OBJECTIVES: I. To determine the rate of voice and swallowing problems. II. To determine the degree to which quality of life (QOL) is compromised. III. To determine the degree to which accurate quality of life measures can be extracted from patient interview narratives using natural language processing techniques. IV. To determine clinical recurrence rates. OUTLINE: Patients are randomized to 1 of 2 treatment arms, if ineligible into a SOC arm. Arm I: Patients undergo total thyroidectomy alone. Arm II: Patients undergo total thyroidectomy with ipsilateral prophylactic central neck dissection (CND). Arm III: Patients ineligible to be randomized into Arm I or II, Standard of Care (SOC) comparator receiving same follow up. After completion of study treatment, patients are followed up at day 1, 2 and 6 weeks, and 6 and 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage I Papillary Thyroid Cancer, Stage II Papillary Thyroid Cancer, Stage III Papillary Thyroid Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
117 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (no CND)
Arm Type
Experimental
Arm Description
Patients undergo total thyroidectomy alone.
Arm Title
Arm II (CND)
Arm Type
Experimental
Arm Description
Patients undergo total thyroidectomy with ipsilateral prophylactic CND.
Arm Title
Arm III (SOC)
Arm Type
Active Comparator
Arm Description
Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference
Intervention Type
Procedure
Intervention Name(s)
Thyroidectomy
Intervention Description
Undergo total thyroidectomy
Intervention Type
Procedure
Intervention Name(s)
entral lymph node dissection (CLND)
Intervention Description
Undergo total thyroidectomy with ipsilateral prophylactic CND
Intervention Type
Other
Intervention Name(s)
Quality-of-life assessment
Intervention Description
Voice evaluation, interviews, ancillary studies
Primary Outcome Measure Information:
Title
Percentage of Participants With Transient Hypoparathyroidism, as Defined by a Day 1 Serum Parathyroid Hormone (PTH) Level of < 10 pg/ml
Description
Rate of transient hypoparathyroidism will be assessed in terms of percentage of participants with day 1 serum PTH level of < 10 pg/ml.
Time Frame
Post-operative day 1
Title
Post-operative Serum Calcium (mg/dL) at Day 12
Description
Post-operative serum calcium (mg/dL) at Day 12
Time Frame
At day 12
Title
Total Calcium Consumption in First 2 Weeks
Description
Total calcium consumption in first 2 weeks (total mg). Participants were given calcium symptom logs in which to record their calcium consumption between surgery and their first preoperative follow up appointment, approximately two week.
Time Frame
2 weeks after surgery
Title
Number of Participants With Hypocalcemia Symptoms in First 2 Weeks
Description
Number of participants with hypocalcemia symptoms and symptom severity in first two weeks, as defined by presence of clinically significant symptoms of hypocalcemia. Clinically significant symptoms defined as 1 or more episodes of symptoms of hypocalcemia per day for multiple days, symptoms leading to calls to provider for assistance with managing and/or symptoms leading to escalation of dosage of prescribed medications to treat symptoms of hypocalcemia
Time Frame
2 weeks
Title
Hypocalcemia Symptom Severity Scale (Range of 1-5)
Description
Mean number of occurrences of mild (severity 1 - 2) and severe (severity 3 - 5) hypocalcemia symptoms. Participants were asked to record hypocalcemia symptoms between surgery and first postoperative follow-up at approximately two weeks in their provided calcium symptom logs and rank severity on scale of 1 (mild) to 5 (severe).
Time Frame
2 weeks post surgery
Title
Percentage of Participants That Required Calcium and Calcitriol at Month 6
Description
Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH <15 pg/ml)
Time Frame
At Month 6
Title
Post-operative Serum PTH (pg/ml) at Month 6
Time Frame
At Month 6
Title
Post-operative Serum Calcium Level at Month 6
Description
Post-operative serum calcium (mg/dL) at Month 6
Time Frame
At Month 6
Secondary Outcome Measure Information:
Title
Rate of Transient and Permanent Hypocalcemia
Description
The rate of transient and permanent hypocalcemia will be determined by assessing the following: I. Post-operative serum calcium (mg/dl) and PTH (pg/ml) at Day 12 and Month 6 II. Total calcium consumption in first 2 weeks (total gm) III. Hypocalcemia symptoms in first 2 weeks (average episodes/day) IV. Hypocalcemia symptom severity scale (range 1-5) V. Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH < 15 pg/ml Data will be analyzed using the methods described above.
Time Frame
Post-operative day 1 - Month 6
Title
Rate of Voice and Swallowing Problems
Description
The rate of voice and swallowing problems will be determined by assessing the following: I. Phonation threshold pressure, in centimeters of water II. Dysphonia severity index (DSI) score (+5 to -5) III. Grade Roughness Breathiness Asthenia Strain (GRBAS) score (0-3) IV. Voice quality parameters as measured by Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) (0-100 on visual analog scale) V. Vocal fold vibratory and movement parameters as measured by stroboscopy assessment (1-4) VI. Glottal function index score VII. Penetration-Aspiration score as measured by videofluoroscopic swallow study (0-8) Data will be analyzed using the methods described above.
Time Frame
Post operative day 1 - up to 1 year
Title
Degree to Which Quality of Life (QOL) is Compromised
Description
The degree to which quality (QOL) is compromised will be determined by assessing the following: I. Short Form Health Survey (SF-12) Mental Composite Scale (MCS) score II. Short Form Health Survey (SF-12) Physical Composite Scale (PCS) score III. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core-30 (C30) score IV. Thyroid Cancer Specific Quality of Life (ThyCA-QOL) score V. 10-item Eating Assessment Tool (EAT-10) dysphagia inventory score VI. Voice Handicap Index (VHI) score VII. Themes and codes from interview transcripts assessed using qualitative research methods Data will be analyzed using the methods described above.
Time Frame
Post-operative day 1 - up to 1 year
Title
Clinical Recurrence Rates
Description
Clinical recurrence rates will be determined by assessing the following: I. Percent of patients with a recombinant thyroid-stimulating hormone (rTSH) stimulated thyroglobulin level < 1 ng/ml one year after surgery II. Unstimulated thyroglobulin level prior to beginning week 6 radioactive iodine treatment III. Stimulated thyroglobulin at the time of week 6 radioactive iodine treatment IV. Incidence of unstimulated thyroglobulin > 1 ng/mL at 6 months V. Incidence of stimulated thyroglobulin > 2 ng/mL at 1 year VI. Incidence of biopsy-proven disease identification on neck ultrasound or iodine-131 (I-131) uptake up to 5 years post-surgery Data will be analyzed using the methods described above.
Time Frame
Week 6 - up to 5 years
Title
Degree to Which Accurate Quality of Life (QOL) Measures Can be Extracted From Patient Interview Narratives Using Natural Language Processing Techniques
Description
The degree to which accurate quality of life (QOL) measures can be extracted from patient interview narratives using natural language process techniques will allow for the development of computer algorithms that convert patient narrative text into simple quality of life measures. Data will be analyzed using the methods described above.
Time Frame
Post-operative day 1 - up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
73 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pre-operative diagnosis or suspicion of papillary thyroid cancer, usually by fine needle aspiration (FNA) No pre-operative evidence of cervical lymph node metastases on neck ultrasound (randomization arms only) No evidence of distant metastases Ability to read and write in English Exclusion Criteria: Largest papillary thyroid carcinoma < 1 cm in size on ultrasound Previous thyroid surgery Concurrent active malignancy of another type Inability to give informed consent or lacks decision making capacity T4 tumor Pre-existing vocal cord paralysis Chronic neurologic condition which affects voice or swallow (for instance, multiple sclerosis or Parkinson disease) Baseline laryngeal pathology that would warrant intervention that could affect voice or swallow function Becomes pregnant before surgery or at any time while on study INTRA-OPERATION EXCLUSION CRITERIA (randomization arms only) Evidence of nodal involvement identified in the operating room (OR) Failure to confirm diagnosis of cancer in participant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rebecca Sippel
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33759836
Citation
Sippel RS, Robbins SE, Poehls JL, Pitt SC, Chen H, Leverson G, Long KL, Schneider DF, Connor NP. A Randomized Controlled Clinical Trial: No Clear Benefit to Prophylactic Central Neck Dissection in Patients With Clinically Node Negative Papillary Thyroid Cancer. Ann Surg. 2020 Sep 1;272(3):496-503. doi: 10.1097/SLA.0000000000004345.
Results Reference
derived
PubMed Identifier
29710208
Citation
Kletzien H, Macdonald CL, Orne J, Francis DO, Leverson G, Wendt E, Sippel RS, Connor NP. Comparison Between Patient-Perceived Voice Changes and Quantitative Voice Measures in the First Postoperative Year After Thyroidectomy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2018 Nov 1;144(11):995-1003. doi: 10.1001/jamaoto.2018.0309.
Results Reference
derived
Links:
URL
https://cancer.wisc.edu/
Description
University of Wisconsin Carbone Cancer Center Homepage

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Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer

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