VIMSELTINIB for Tenosynovial giant cell tumor

Inclusion criteria

• {"criterion_text":"- Male or female participants ≥18 years of age\n- Participants of reproductive potential must: a. Have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening (female participants). b. Agree to follow the contraception requirements outlined in the protocol\n- The participant is capable of understanding and complying with the protocol and has signed the informed consent form (ICF). A signed ICF must be obtained before any study-specific procedures are performed.\n- Willing and able to complete the PRO assessments on an electronic device\n- Histologically confirmed diagnosis of TGCT (formerly known as pigmented villonodular synovitis [PVNS] or giant cell tumor of the tendon sheath [GCT-TS]). Tumor biopsy to confirm TGCT diagnosis will be required if no histology/pathology is available. a. Participants should have TGCT in a single joint and must have TGCT in joints where ROM can be assessed\n- Disease for which surgical resection will potentially cause worsening functional limitation or severe morbidity as judged by surgical consultation or a multidisciplinary tumor board\n- Symptomatic disease with at least moderate pain or at least moderate stiffness (defined as a score of 4 or more, with 10 describing the worst condition) within the screening period and documented in the medical record\n- Participant should complete 14 consecutive days of questionnaires during the screening period and must meet minimum requirements outlined in Protocol Table 4\n- An analgesic regimen, if used, needs to be stable( ie, no change in dose) as judged by the Investigator for at least 2 weeks prior to the first dose of study drug\n- Measurable disease per RECIST v1.1 with at least one lesion having a minimum size of 2 cm as assessed from magnetic resonance imaging (MRI) scans by a central radiologist\n- Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed within 21 days prior to the first dose of study drug: a. Bone marrow function: absolute neutrophil count (ANC) ≥1500/μL; hemoglobin ≥10 g/dL; platelet count ≥lower limit of normal (LLN). b. Hepatic function: total serum bilirubin ≤upper limit of normal (ULN); serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ULN. c. Renal function: creatinine clearance ≥50 mL/min based either on urine collection or Cockcroft-Gault estimation. d. Electrolytes ≥LLN for: potassium, magnesium, and calcium\n- Able to take oral medication"}

Exclusion criteria

• {"criterion_text":"- Previous use of systemic therapy (investigational or approved) targeting CSF1 or CSF1R including vimseltinib; previous therapy with imatinib and nilotinib is allowed\n- Known active human immunodeficiency virus (HIV), acute or chronic hepatitis B, acute or chronic hepatitis C, or known active mycobacterium tuberculosis infection\n- If female, the participant is pregnant or breastfeeding\n- Known allergy or hypersensitivity to any component of the study drug\n- Contraindication to MRI\n- Treatment for TGCT, including investigational therapy, during the screening period. NOTE: Participants may not be part of an ongoing or have prior participation in a non TGCT investigational drug study within 30 days of screening. Ongoing participation in a noninterventional study (including observational studies) is permitted\n- Known metastatic TGCT or other active cancer that requires concurrent treatment (exceptions will be considered on a case-by-case basis depending on tumor type, stage, location, planned treatment, and expected recovery after discussion and approval by Sponsor)\n- Baseline prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT syndrome\n- Receive concurrent treatment with any prohibited medications • Acetaminophen usage exceeding 3 g/day • Proton-pump inhibitors taken within 4 days prior to the first dose of study drug • Medications that are breast cancer resistance protein (BCRP) or organic cation transporter 2 (OCT2) substrates taken within at least 4 days or 5×half-life (whichever is longer) prior to the first dose of study drug • Medications with a known risk of prolonging the QT interval within at least 14 days or 5×half-life (whichever is longer) prior to the first dose of study drug (see Appendix 1) • Prophylactic use of myeloid growth factors (eg, granulocyte colonystimulating factor [G-CSF], granulocyte macrophage-colony-stimulating factor [GM-CSF])\n- Major surgery within 14 days of the first dose of study drug; following major surgeries >14 days prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence\n- Any clinically significant comorbidities, such as significant concomitant arthropathy not related to TGCT in the affected joint, or any other serious medical or psychiatric condition(s), known current alcohol abuse, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the participant to safety risks\n- Active liver or biliary disease including non-alcoholic steatohepatitis (NASH), or cirrhosis\n- Malabsorption syndrome or other illness that could affect oral absorption as judged by the Investigator"}

Primary endpoints

• {"endpoint_text":"- Objective response rate (ORR, including complete response [CR] and partial response [PR]) per RECIST v1.1 at Week 25","definition_or_measurement_approach":"ORR per RECIST v1.1 at Week 25 assessed by blinded independent radiological review (IRR)"}

Secondary endpoints

• {"endpoint_text":"- ORR per TVS at Week 25","definition_or_measurement_approach":"ORR assessed using tumor volume score (TVS) at Week 25 (by blinded IRR)"}
• {"endpoint_text":"- Change from baseline in active ROM of the affected joint, relative to a reference standard, at Week 25","definition_or_measurement_approach":"Change from baseline in active range of motion (ROM) of affected joint compared to a reference standard at Week 25"}
• {"endpoint_text":"- Change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) physical function score at Week 25","definition_or_measurement_approach":"Change from baseline in PROMIS physical function score at Week 25 (PRO instrument)"}
• {"endpoint_text":"- Change from baseline in the Worst Stiffness numeric rating scale (NRS) score at Week 25","definition_or_measurement_approach":"Change from baseline in Worst Stiffness NRS score at Week 25 (patient-reported)"}
• {"endpoint_text":"- Change from baseline in EQ-VAS (EuroQol Visual Analogue Scale) at Week 25","definition_or_measurement_approach":"Change from baseline in EQ-VAS at Week 25 (patient-reported health status)"}
• {"endpoint_text":"- Response of at least a 30% improvement in the mean Brief Pain Inventory (BPI) Worst Pain NRS score without a 30% or greater increase in narcotic analgesic use at Week 25","definition_or_measurement_approach":"At least 30% improvement in mean BPI Worst Pain NRS score at Week 25 without ≥30% increase in narcotic analgesic use"}
• {"endpoint_text":"- ORR per RECIST v1.1","definition_or_measurement_approach":"ORR assessed per RECIST v1.1 (no specific timepoint given beyond Week 25 assessments)"}
• {"endpoint_text":"- ORR assessed by mRECIST at Week 25","definition_or_measurement_approach":"ORR assessed by modified RECIST (mRECIST) at Week 25"}
• {"endpoint_text":"- Duration of response (DOR; time from first PR or CR to disease progression or death) assessed using RECIST v1.1, TVS, and mRECIST","definition_or_measurement_approach":"DOR defined as time from first PR/CR to progression or death; assessed by RECIST v1.1, TVS, and mRECIST"}
• {"endpoint_text":"- Incidence of treatment-emergent adverse events (TEAEs), treatmentemergent serious adverse events, related TEAEs, dose reductions, dose interruptions, and discontinuation of study drug due to adverse event","definition_or_measurement_approach":"Safety endpoints: incidence and characterization of TEAEs, serious TEAEs, related TEAEs, dose modifications and discontinuations"}
• {"endpoint_text":"- Changes from baseline in laboratory parameters, electrocardiograms (ECGs), and vital signs","definition_or_measurement_approach":"Changes from baseline in labs, ECGs and vital signs (safety monitoring)"}

Germany

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

03-07-2024

Processing Time Days

23

Number Of Sites

2

Number Of Participants

8

Netherlands

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

28-06-2024

Processing Time Days

18

Number Of Sites

1

Number Of Participants

14

Norway

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

02-07-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

05-07-2024

Processing Time Days

25

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

01-07-2024

Processing Time Days

21

Number Of Sites

2

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

29-07-2024

Processing Time Days

49

Number Of Sites

4

Number Of Participants

17

Spain

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

16-07-2024

Processing Time Days

36

Number Of Sites

3

Number Of Participants

15

Primary sponsor

Full Name

Deciphera Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Worldwide Clinical Trials Early Phase Services LLC

Responsibilities

PK analysis

Name

Fortrea Inc.

Name

Labcorp Central Laboratory Services SARL

Name

PCI Pharma Services Germany GmbH

Responsibilities

Site of Importation - EU

Name

Advanced Clinical LLC

Third parties

• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Kcas LLC","duties_or_roles":"PD analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Patient travel vendor","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Worldwide Clinical Trials Early Phase Services LLC","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta Biosciences","duties_or_roles":"Immunophenotyping-flow cytometry","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Llx Solutions LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Advanced Clinical LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinical Ink Inc.","duties_or_roles":"Collection of patient reported outcome","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"Site of Importation - EU","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Spire Sciences LLC","duties_or_roles":"Medical image analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Evidera Inc.","duties_or_roles":"Patient interviews","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Vivos Technology Limited","duties_or_roles":"DMC coordination and Independent Data Analysis Center for DMC data reviews","organisation_type":"Non-Pharmaceutical company"}