XL092 in Patients With Metastatic Castration-Resistant Prostate Cancer

Recruitment & Eligibility

Status: Not yet recruiting

Sex: Male

Target Recruitment: 32

Inclusion Criteria

Inclusion Criteria: - Participant aged = 18 years - Disease criteria: - Histologically or cytologically confirmed prostatic adenocarcinoma without small cell histology - Radiographic evidence of metatstatic disease - Progression on or after prior treatment with 117Lu-PSMA-617 as determined by clinical investigator - ECOG Performance Status = 2. - Adequate organ function as defined as: --Absolute neutrophil count = 1500/mm3 . - Platelet count = 100,000/mm3 . - Hemoglobin = 9 g/dL . - Total Bilirubin = 1.5x institutional ULN. For subject's with Gilbert's disease, = 3 x ULN. - Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) = 3 x ULN. For subjects with documented bone metastasis ALP = 5 x ULN. For subjects with CRPC and bone metastasis ALP = 10 x ULN if predominantly bone-specific ALP. - International Normalized Ratio (INR) = 1.5 and activated partial thromboplastin time (aPTT) = 1.2 upper limit of normal (ULN) - Serum creatinine = 1.5 x ULN or estimated creatinine clearance = 40 mL/min by Cockcroft-Gault formula: ---Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72) - Urine protein-to-creatinine ratio (UPCR) = 1.5 mg/mg (= 169.8 mg/mmol) creatinine or 24-hour urine protein <1.5 g. - Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Section 5.4.1) during the course of the study and for 96 days after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm for the purpose of reproduction during these same periods. - Must have recovered from adverse effects of any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy). CTCAE adverse events less than or equal to grade 1 are acceptable. CTCAE adverse events grade 2 or greater may be acceptable as determined by the Clinical Investigator. - Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: - Prior treatment with XL092 - Receipt of any type of small molecule kinase inhibitor, cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks or at least 5 half-lives, whichever shorter before first dose of study treatment. Note: Concomitant use of megestrol acetate, androgen-deprivation therapy and bone loss prevention treatment is permitted. Other types of hormonal therapies with similar use require prior approval from the Principal Investigator. - Radiation therapy for bone metastasis or any other radiation therapy within 2 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. - Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Subjects with an incidental finding of an isolated brain lesion < 1 cm in diameter may be eligible after Principal Investigator approval if the lesion is radiographically stable for 4 weeks before first dose and does not require treatment per Investigator judgement. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment. -Concomitant anticoagulation with oral anticoagulants except for those specified below:- - (a) Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose low molecular weight heparins (LMWH) or prophylactic dose of specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban - (b) Therapeutic doses of LMWH or specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before enrollment and without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor. -Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks or at least 5 half-lives, whichever shorter before first dose of study treatment. -The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: - Cardiovascular disorders: - Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias [eg, ventricular flutter, ventricular fibrillation, Torsades de pointes (TdP)]. - Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment. - Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant ischemic event within 6 months before first dose of study treatment. - Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA/TIA arterial thromboembolic events within 3 months before to first dose of study treatment. Note: Subjects with a diagnosis of DVT within 3 months are allowed if asymptomatic and stable at screening and treated with anticoagulation per standard of care before first dose of study treatment. Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator. - Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: ---Tumors invading the GI-tract from external viscera ---Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis ---Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless cause of obstruction is definitively managed and subject is asymptomatic ---Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment. ---Known gastric or esophageal varices -Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study treatment. - Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. - Lesions invading major blood vess

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of participants with non-progressive disease after 16 weeks of treatment with XL092 as assessed by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1

Secondary Outcome Measures