A phase 3, randomized, placebo-controlled, double-blind study of vimseltinib to assess the efficacy and safety in patients with tenosynovial giant cell tumor (MOTION)
- Conditions
- Advanced tumorsrare tumor arising from the jointsTenosynovial Giant Cell Tumor1001336110041294
- Registration Number
- NL-OMON56439
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
Participants must meet all of the following criteria to be eligible to enroll
in the study:
1. Male or female participants >=18 years of age
2. 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 assessments can be assessed
3. Disease for which surgical resection will potentially cause worsening
functional limitation or severe morbidity as judged by surgical consultation or
a multidisciplinary tumor board
4. 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
5. Participants should complete 14 consecutive days of questionnaires during
the screening period and must meet minimum requirements outlined in Table 4
6. 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
7. 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
8. 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
9. Able to take oral medication
10. 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
11. 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
12. Willing and able to complete the PRO assessments on an electronic device
Participants meeting any of the following criteria will be excluded from the
study:
1. Previous use of systemic therapy (investigational or approved) targeting
CSF1 or CSF1R including vimseltinib; previous therapy with imatinib and
nilotinib is allowed
2. 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.
3. 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)
4. 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
5. 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
colony-stimulating factor [G CSF], granulocyte macrophage-colony-stimulating
factor [GM-CSF])
6. 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
7. 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
8. Active liver or biliary disease including nonalcoholic steatohepatitis
(NASH) or cirrhosis
9. Malabsorption syndrome or other illness that could affect oral absorption
as judged by the Investigator
10. Known active human immunodeficiency virus (HIV), acute or chronic hepatitis
B, acute or chronic hepatitis C, or known active mycobacterium tuberculosis
infection
11. If female, the participant is pregnant or breastfeeding
12. Known allergy or hypersensitivity to any component of the study drug
13. Contraindication to MRI
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>• Objective response rate (ORR, including complete response [CR] and partial<br /><br>response [PR]) per RECIST v1.1 at Week 25</p><br>
- Secondary Outcome Measures
Name Time Method