Tenosynovial giant cell tumor (TGCT) Cell Tumor
Conditions
Interventions
None listed
Sponsors
Deciphera Pharmaceuticals LLC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria (Dose Escalation Phase) Patients must meet all of the following criteria to be eligible to enroll in the Dose Escalation phase of the study: 1) Male or female patients >=18 years of age 2) Any of the following solid tumors: a) Advanced MST that has progressed after treatment with all available therapies known to confer clinical benefit or for which conventional therapy is not considered effective as judged by the Investigator: i) Solid tumors, including but not limited to, metastatic breast or prostate cancer with bone disease ii) Solid tumors including, but not limited to, gastric, ovarian or non-small cell lung cancer (NSCLC) that frequently have malignant associated ascites or effusion(s) iii) Tumors with known contribution of macrophages or phagocytes such as but not limited to: (1) Tumors with high tumor-infiltrating macrophage content (2) Tumor types with high expression of the receptor CSF1R or its ligands, CSF1 or IL-34, in the tumor by previous testing (3) Prostate or breast cancer with bone-only disease iv) NSCLC patients with: (1) Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC with a known epidermal growth factor receptor (EGFR) mutation(s) (2) Documented disease progression while on a previous treatment with an EGFR tyrosine kinase inhibitor b) TGCT patients: Histologically confirmed diagnosis of TGCT (formerly known as pigmented villonodular synovitis or giant cell tumor of the tendon sheath). Tumor biopsy to confirm TGCT diagnosis will be required if no histology/pathology is available at the time of screening i) Disease for which surgical resection will potentially cause worsening functional limitation or severe morbidity as judged by the Investigator ii) Symptomatic disease with at least moderate pain or stiffness (a score of 4 or more with 10 describing the worst condition) within 1 month of the first dose documented in the medical record iii) Prior treatment with anti-CSF1 or anti-CSF1R therapy is allowed (1) Exception 1: discontinuation of anti-CSF1 or anti-CSF1R due to drug-induced liver injury 3) MST patients only: Able to provide a tumor tissue sample; if an archival tumor tissue sample is unavailable, patients must be willing to undergo a tumor biopsy prior to the first dose of study drug, if the tumor is accessible to biopsy and, in the judgment of the Investigator, the tumor biopsy will be done safely 4) Patients must have at least 1 measurable lesion according to RECIST Version 1.1 (non-nodal lesions must be >=1.0 cm in the long axis or >=double the slice thickness in the long axis; nodal lesions must be >=1.5 cm in the short axis) except for prostate or breast cancer patients with bone-only disease a) A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion before study enrollment b) Prostate or breast cancer patients with bone-only disease are eligible without a measurable lesion by RECIST Version 1.1 5) MST patients only: Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 6) Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed within 14 days pri
Exclusion criteria
Exclusion criteria: Exclusion Criteria (Dose Escalation Phase) Patients meeting any of the following criteria will be excluded from the Dose Escalation phase of the study: 1. Treatment with anticancer therapy, therapy for TGCT, including investigational therapy, within 2 weeks prior to the administration of study drug. For immediately prior therapies with a half-life (t1/2) longer than 3 days, or if the t1/2 is not available, the interval must be >=28 days prior to the first administration of study drug 2. Unresolved toxicity according to NCI-CTCAE, Version 4.03 (ie, Grade >1 or baseline) from previous anticancer or TGCT therapy, excluding alopecia 3. The patient has known active central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided that: a. They are stable (ie, no evidence of progression by magnetic resonance imaging [MRI]) for at least 4 weeks prior to the first dose of study drug), b. All neurologic symptoms have returned to baseline, and c. Patients do not require continued steroid therapy or use of enzyme-inducing antiepileptic drugs. Patients can be switched to a non-enzyme inducing antiepileptic drug. If signs or symptoms suggest CNS metastases, a brain MRI/computed tomography (CT) scan must be performed to confirm absence of detectable CNS disease within 2 weeks prior to receiving study drug. 4. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure 5. Systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months prior to the start of study drug 6. Systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within the 1 month prior to the start of study drug 7. Baseline prolongation of the QTcF based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT syndrome 8. LVEF 2 weeks prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence 11. Any other clinically significant comorbidities, such as significant concomitant arthropathy 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 patient to safety risks 12. Malabsorption syndrome or other illness that could affect oral absorption as judged by the Investigator 13. Known human immunodeficiency virus, active hepatitis B, active hepatitis C, or active mycobacterium tuberculosis infection 14. If female, the patient is pregnant or lactating 15. Known allergy or hypersensitivity to any component of the study drug Exclusion Criteria (Expansion Phase, TGCT Patients) Patients meeting any of the following criteria will be excluded from the Expansion phase: 1. Expansion Cohor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints: Safety: DLTs, treatment emergent adverse events (TEAEs), serious adverse events (SAEs), dose reduction or discontinuation of study drug due to toxicity, physical examination findings, ECOG PS, changes from baseline in laboratory parameters, electrocardiograms (ECGs), LVEF, and vital signs. Pharmacokinetics: The following PK endpoints, including but not limited to, will be evaluated for both DCC-3014 parent and its metabolite, DP 7005, if detected: • Time to maximum observed concentration (Tmax). • Maximum observed concentration (Cmax). • Trough observed concentration (Cmin). • Area under the concentration time curve (AUC). • t1/2. Efficacy (TGCT Expansion Cohort A only): • Objective response rate (ORR=complete response [CR]+partial response [PR]) assessed by independent radiological review using RECIST Version 1.1 at Week 25 (Cycle 7 Day 1). • Duration of Response (DOR; time from PR or CR to disease progression or death). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints (TGCT Expansion Cohort A only): • ORR assessed by independent radiological review using TVS and mRECIST. Functional Assessments: • ROM: change from baseline to Week 25 (Cycle 7 Day 1). • Response based on BPI worst pain NRS and narcotic analgesic use by Brief Pain Inventory-30 (BPI-30) at Week 25 (Cycle 7 Day 1). • PRO based upon the PROMIS physical function questionnaire and worst stiffness NRS: * Change from starting value to Week 25 (Cycle 7 Day 1). Exploratory Endpoints: Preliminary Evidence of Antitumor Activity: The following endpoints documenting preliminary evidence of DCC 3014 will be evaluated: • ORR=CR+PR • Clinical Benefit=CR+PR+stable disease) at Weeks 9 (Cycle 3 Day 1), 25 (Cycle 7 Day 1), and 49 (Cycle 13 Day 1) • Time to best response (defined as time from Cycle 1 Day 1 to PR or CR) • Progression-free-survival (defined as time from Cycle 1 Day 1 to disease progression or death), except for TGCT patients • DOR (defined as time from PR or CR to disease progression or death; Dose Escalation and Expansion Cohort B) Tumor response will be assessed by tumor type using the following criteria: • MST and TGCT: RECIST, Version 1.1 • TGCT: mRECIST • TGCT: TVS • For bone-only disease: a new lesion(s) identified by bone scan will be considered as disease progression (see Section 6.9.2) • TGCT: ROM mean changes from baseline PROs (TGCT only and not covered above in secondary endpoints): Note: Where Cycle 7 Day 1 is mentioned below, the PRO estimate will be calculated by taking the average of the PRO scores from Weeks 2 and 3 of Cycle 6. • Response based on BPI average pain NRS and narcotic analgesic use by BPI-30 at Week 25 (Cycle 7 Day 1) • 36-item short form survey (SF 36; Dose Escalation only), EQ-5D-5L, and NRS about *swelling* and *instability* on a scale of 0 to 10 as: * Change from mean starting value to the Week 25 (Cycle 7 Day 1) endpoint • GP5 *burden-of-side-effects* question from the FACT-G * Pr | — |
Countries
Netherlands
Outcome results
None listed