Neoadjuvant Pimicotinib Combined With Surgery Versus Upfront Surgery for Diffuse Tenosynovial Giant Cell Tumor (NEXPERT)

July 12, 2026 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

Neoadjuvant Pimicotinib Combined With Surgery Versus Upfront Surgery for Diffuse Tenosynovial Giant Cell Tumor: A Randomized, Open-label Trial

Tenosynovial giant cell tumor (TGCT) is a rare neoplasm predominantly occurring in young and middle-aged adults, characterized by high recurrence and high disability rates. Surgery represents the first-line treatment at present. Although surgical resection can eradicate lesions, repeated surgical interventions constitute the major disease-related burden. Particularly for patients with diffuse-type TGCT (D-TGCT), postoperative recurrence rates can exceed 50%.

Pimicotinib is a highly selective colony-stimulating factor 1 receptor (CSF1R) inhibitor. The phase III MANEUVER trial has verified its prominent tumor shrinkage effect and symptomatic improvement in patients with unresectable, symptomatic TGCT, with an objective response rate (ORR) of 54%. In addition, pimicotinib demonstrates a favorable safety profile; most adverse events are mild in severity, mainly including pruritus, edema, fatigue and elevated creatine kinase, without severe hepatotoxicity.

Neoadjuvant therapy followed by surgery falls within the scope of multimodal treatment, which is mostly applied to recurrent and refractory cases rather than the standard upfront regimen for treatment-naive patients. Clinical case reports and real-world observations have preliminarily validated the feasibility and clinical value of sequential systemic targeted therapy followed by surgical resection. To date, systematic and standardized clinical data regarding neoadjuvant strategies remain scarce, especially randomized controlled evidence comparing neoadjuvant targeted therapy plus surgery versus primary upfront surgery. This study aims to compare the efficacy and safety of neoadjuvant pimicotinib combined with surgery versus upfront primary surgery in the management of D-TGCT, so as to generate evidence-based rationale for developing more effective and safe therapeutic regimens for D-TGCT.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

84

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310000
        • Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female subjects aged ≥18 years
  • Histologically confirmed tenosynovial giant cell tumor (TGCT)
  • Resectable diffuse tenosynovial giant cell tumor (D-TGCT) were determined by multidisciplinary team (MDT) discussion.
  • Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 with at least one lesion of ≥2 cm
  • Symptomatic disease with a worst pain of at least 4 or/and a worst stiffness of at least 4 (based on a scale of 0-10 with 10 describing the worst condition) prior to randomization Adequate organ and bone marrow function
  • Adequate organ function and bone marrow function
  • Willing and able to complete patient-reported outcome (PRO) assessments throughout the study.

Exclusion Criteria:

  • Prior treatment with highly selective Colony-Stimulating Factor 1 (CSF1)/ Colony-Stimulating Factor 1 Receptor (CSF1R) inhibitors before randomization
  • Presence of another malignancy requiring active treatment, in the investigator's judgment, which may interfere with study participation or results
  • Known metastatic TGCT
  • Severe concomitant arthropathy, severe illness, or uncontrolled infection in the affected joint
  • Significant factors affecting oral drug absorption
  • Concomitant use of strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days before randomization
  • Impaired cardiac function or severe cardiac disease
  • Known active Human Immunodeficiency Virus (HIV) infection, active hepatitis B, active hepatitis C, or active tuberculosis before randomization
  • Known active liver or biliary disease, or other conditions that may cause abnormal liver function tests during the study
  • Pregnant or lactating female (pregnancy defined as from conception until termination)
  • Fertile males or non-sterilized females who do not agree to use effective contraception from at least 14 days before randomization until 6 months after the last dose of study drug
  • Other serious comorbidities that, in the investigator's judgment, may affect protocol compliance, interfere with interpretation of study results, or increase the patient's risk of safety events

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant Therapy plus Surgery
Patients take neoadjuvant pimicotinib first, then undergo subsequent surgical resection of the lesion.
Drug: Pimicotinib
Pimicotinib 50 mg orally once daily for 12 consecutive weeks.
Procedure: Tumor resection surgery
Open surgery will be performed based on patient and tumor characteristics discussed at the multidisciplinary team (MDT) meeting. The specific surgical plan will be determined by the surgeon based on clinical judgment. Surgical procedures will follow national guidelines.
Active Comparator: Upfront Surgery
Patients undergo surgical tumor resection right after study enrollment.
Procedure: Tumor resection surgery
Open surgery will be performed based on patient and tumor characteristics discussed at the multidisciplinary team (MDT) meeting. The specific surgical plan will be determined by the surgeon based on clinical judgment. Surgical procedures will follow national guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival
Time Frame: 2 years
Events are defined as disease progression precluding planned surgery, local recurrence, distant metastasis, treatment discontinuation due to adverse events, or death from any cause.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local recurrence rate
Time Frame: 2 year
2 year
Surgical complication rate
Time Frame: 2 years
2 years
Change in range of motion
Time Frame: 2 years
2 years
Change in Brief Pain Inventory (BPI)
Time Frame: 2 years
Score range: 0-10; Higher scores mean more severe pain and greater life interference; lower scores mean pain relief.
2 years
Change in stiffness Numerical Rating Scale (NRS)
Time Frame: 2 years
Score range: 0-10; Higher score means worse joint stiffness; reduced score indicates improvement.
2 years
Change in Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) score
Time Frame: 2 years
This PROMIS Physical Function short form contains items with 5-point Likert response (1=unable to do, 5=no difficulty at all).The raw score from these responses is then converted to a standardized T-score on a scale of 0 to 100, with a mean of 50 and a standard deviation of 10. The total score is the final T-score. Higher T-score indicates better physical function.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2027

Primary Completion (Estimated)

September 30, 2029

Study Completion (Estimated)

September 30, 2030

Study Registration Dates

First Submitted

July 3, 2026

First Submitted That Met QC Criteria

July 12, 2026

First Posted (Actual)

July 16, 2026

Study Record Updates

Last Update Posted (Actual)

July 16, 2026

Last Update Submitted That Met QC Criteria

July 12, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-0643

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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