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Subject (or legal guardian where applicable) is willing and able to provide signed informed consent (or assent when applicable) and can follow protocol requirements |
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Subject must have histologically- or cytologically-confirmed disease with unresectable or metastatic disease, following at least 1 prior line of standard-of-care systemic therapy (systemic therapy may be administered with or without the use of surgery or radiation) and must not be candidates for therapies available that are known to confer clinical benefit |
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Synovial sarcoma |
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SMARCB1-null tumor as determined by immunohistochemistry, fluorescent in situ hybridization, or other equivalent tests like gene mutation analysis |
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Subjects must be ≥18 years of age or ≥16 years old and weighs ≥50 kg |
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Subject must have measurable disease as defined by RECIST v1.1 |
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Subject must have Eastern Cooperative Oncology Group performance status ≤2 |
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Adolescent enrichment cohort: Lansky performance scale (LK scale): ≥60 |
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Subject must have adequate organ function, defined as |
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Bone marrow function: absolute neutrophil count ≥1.0 x 109/L independent of growth factor support for ≤7 days prior to first dose of study drug for granulocyte colony-stimulating factor and ≤14 days prior to first dose of study drug for pegfilgrastim; hemoglobin ≥8 g/dL independent of transfusion support for ≤7 days prior to first dose of study drug; platelet count ≥75 x 109 /L independent of transfusion support for ≤3 days prior to first dose of study drug |
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Coagulation: Prothrombin time (PT)/international normalized ratio (INR) <1.5x the upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) <1.5x ULN (unless the subject is receiving anticoagulant therapy and INR and partial PT/aPTT are within therapeutic range of intended use of anticoagulants) |
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Liver function: total bilirubin ≤1.5x ULN (≤3.0x ULN for subjects with Gilbert's syndrome), aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0x ULN; except for subjects who have tumor infiltration of the liver, where ALT and AST ≤5x ULN |
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Renal function: must have a creatinine clearance ≥60 mL/min (Cockcroft-Gault equation) |
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Cardiac function: baseline corrected QT interval using Fredericia's formula ≤470 ms (adolescents 12-17 years of age: ≤450 ms) and a left ventricular ejection fraction ≥50% evaluated via echocardiogram |
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A female subject may be eligible to participate if she is not pregnant or planning a |
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pregnancy, not breastfeeding, and following protocol mediated guidance to |
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avoid pregnancy |
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A male subject must have either had a prior vasectomy or agree to use a condom during the treatment period and for at least 90 days after the last dose of study treatment |
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Subject has received major surgery within 3 weeks prior to the planned first dose of CFT8634
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Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment
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Subject has received standard of care or investigational systemic anti-neoplastic
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therapy within 14 days or 5 half-lives, whichever is shorter, prior to the
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planned first dose of CFT8634
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Subject has received radiation therapy within 14 days prior to the planned first dose of CFT8634
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Subjects with central nervous system (CNS) involvement (primary tumor or metastatic disease), except in the following circumstances
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Subjects with previously treated brain metastases may be permitted to participate provided they are stable (without evidence of progression by imaging 4 weeks prior to the first dose of study treatment and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and, if they are taking corticosteroids, they are on stable or tapering doses for at least 7 days prior to first dose of study treatment. Antiseizure therapy is permitted provided the medication is not otherwise excluded and seizures have been controlled for at least 4 weeks since the last antiseizure medication adjustment
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Subjects with asymptomatic brain metastases found on screening magnetic resonance imaging (MRI) may be permitted to be entered into the study without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant
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Subject has any evidence of a CNS bleed including intratumoral hemorrhage
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Subject has known bleeding diathesis
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Subject has impaired cardiac function or clinically significant cardiac disease
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Subjects with presence of inflammatory vascular disease or microangiopathy (eg, thrombotic microangiopathies, hemolytic uremic syndrome [HUS], atypical HUS)
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Subject with known malignancy, other than study indication, that is progressing or has required treatment within the past 3 years
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Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
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Subjects with known history of human immunodeficiency virus (HIV) infection
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Subjects with a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or at risk for HBV/HCV infection must have a negative HBV/HCV test to be considered eligible for this study
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