Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer

NCT02138214 | Completed Phase 2 Results DMC

• 6 other identifiers: UW13115NCI-2014-00833R01CA1769112014-0391A539700SMPH\SURGERY\SURGERY
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

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.

Conditions

Stage I Papillary Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage III Papillary Thyroid Cancer

Outcome Measures

Primary Outcomes (8)

• 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 day 1

• Post-operative Serum Calcium (mg/dL) at Day 12

  Post-operative serum calcium (mg/dL) at Day 12

  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.

  2 weeks after surgery

• 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

  2 weeks

• 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).

  2 weeks post surgery

• 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)

  At Month 6

• Post-operative Serum PTH (pg/ml) at Month 6

  At Month 6

• Post-operative Serum Calcium Level at Month 6

  Post-operative serum calcium (mg/dL) at Month 6

  At Month 6

Secondary Outcomes (5)

• Rate of Transient and Permanent Hypocalcemia

  Post-operative day 1 - Month 6

• Rate of Voice and Swallowing Problems

  Post operative day 1 - up to 1 year

• Degree to Which Quality of Life (QOL) is Compromised

  Post-operative day 1 - up to 1 year

• Clinical Recurrence Rates

  Week 6 - up to 5 years

• Degree to Which Accurate Quality of Life (QOL) Measures Can be Extracted From Patient Interview Narratives Using Natural Language Processing Techniques

  Post-operative day 1 - up to 1 year

Study Arms (3)

Arm I (no CND)

EXPERIMENTAL

Patients undergo total thyroidectomy alone.

Procedure: Thyroidectomy; Other: Quality-of-life assessment

Arm II (CND)

EXPERIMENTAL

Patients undergo total thyroidectomy with ipsilateral prophylactic CND.

Procedure: Thyroidectomy; Procedure: entral lymph node dissection (CLND); Other: Quality-of-life assessment

Arm III (SOC)

ACTIVE COMPARATOR

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

Other: Quality-of-life assessment

Interventions

Thyroidectomy PROCEDURE

Undergo total thyroidectomy

Arm I (no CND); Arm II (CND)

entral lymph node dissection (CLND) PROCEDURE

Undergo total thyroidectomy with ipsilateral prophylactic CND

Arm II (CND)

Quality-of-life assessment OTHER

Voice evaluation, interviews, ancillary studies

Arm I (no CND); Arm II (CND); Arm III (SOC)

Eligibility Criteria

• Age: 21 Years - 73 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• Knigge MA, Robbins D, Thibeault S, Connor N, Sippel R. Secondary analyses of swallowing efficiency and safety outcomes following thyroidectomy versus thyroidectomy plus prophylactic central neck dissection. Thyroid Res. 2025 Sep 16;18(1):45. doi: 10.1186/s13044-025-00264-5.

  PMID: 40954474 DERIVED

• 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.

  PMID: 33759836 DERIVED

• 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.

  PMID: 29710208 DERIVED

Related Links

• University of Wisconsin Carbone Cancer Center Homepage

MeSH Terms

Conditions

Thyroid Cancer, Papillary

Interventions

Thyroidectomy

Condition Hierarchy (Ancestors)

Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Thyroid Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Endocrine Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Rebecca Sippel
• Organization: University of Wisconsin, Madison

sippel@surgery.wisc.edu

608-263-1387

Study Officials

• Rebecca Sippel

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2014
• First Posted: May 14, 2014
• Study Start: June 6, 2014
• Primary Completion: October 30, 2019
• Study Completion: October 26, 2020
• Last Updated: December 21, 2020
• Results First Posted: December 21, 2020

Record last verified: 2020-02

Locations

US (1)