Pacritinib for Biochemical Relapse After Definitive Treatment for Prostate Cancer

Inclusion Criteria: 1. Patients aged ≥ 18 years. 2. Histologically or cytologically confirmed prostate adenocarcinoma. 3. Prior radical prostatectomy or definitive radiation. 4. Biochemically recurrent prostate cancer with PSA doubling time ≤ 9 months at the time of study entry (calculated per Memorial Sloan Kettering Cancer Center (MSKCC) prostate nomogram: https://www.mskcc.org/nomograms/prostate/psa\_doubling\_time). Calculation of PSA doubling time should include the use of all available PSA values obtained within the past 12 months prior to randomization, with a minimum of three values separated by at least two weeks apart. The PSA values used to calculate the PSA doubling time must all be ≥ 0.1 ng/mL and should be measured in the same laboratory whenever feasible. 5. Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical assessment of disease characteristics and patient comorbidities. (N/A for patients who underwent definitive radiation therapy). 6. Screening PSA \> 0.5 ng/mL. 7. No definitive evidence of metastases on screening computerized tomography scan (CT) or magnetic resonance imaging (MRI) of abdomen/pelvis and radionuclide whole-body bone scan per the judgment of the investigator. Abdominal and/or pelvic lymph nodes measuring 1.5 cm or less in short axis diameter are allowed. Lesions identified on other imaging modalities (e.g. prostate specific membrane antigen (PSMA) or choline positron emission tomography (PET)) that are not visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal lesions on bone scan should be followed up with additional imaging as clinically indicated. 8. Screening serum testosterone \> 150 ng/dL. 9. Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1 or Karnofsky Performance Status ≥ 70. 10. No prior Janus Kinase 2 (JAK2) inhibitor treatment. 11. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following: • Practice effective barrier contraception during the entire study period and through 60 calendar days after the last dose of study agent 12. Ability to understand a written informed consent document, and the willingness to sign it. 13. Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition (MUGA) scan. 14. Willing to provide blood and tissue for research analysis. (encouraged but not necessary for inclusion in trial). 15. Adequate organ function as defined by the following laboratory values at screening: * Serum aspartate transaminase (AST), serum glutamic oxaloacetic transaminase (SGOT) and serum alanine transaminase (ALT), serum glutamic pyruvic transaminase (SGPT) \< 2.5 x upper limit of normal (ULN). * Total serum bilirubin ≤1.5 x ULN. In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, the subject may be eligible). * Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed. * Estimated glomerular filtration rate (GFR) \> 45 ml/min using Cockroft-Gault equation. * Platelets ≥ 100,000/mL independent of transfusion and/or growth factors within three months prior to randomization. * Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within three months prior to randomization. * Absolute neutrophil count ≥500/µL. * Serum albumin ≥ 3.0 g/dL. * Adequate coagulation defined by prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1x.5 ULN. Exclusion Criteria: 1. Previously treated with pacritinib. 2. Prior systemic treatment with androgen deprivation therapy and/or first-generation anti-androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior androgen deprivation therapy (ADT) and/or first-generation anti-androgen in the (neo)adjuvant, definitive and/or salvage setting in conjunction with radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti-androgen is \> 9 months prior to the date of randomization and the total duration of prior therapy is ≤ 36 months. 3. Prior treatment with 17α-hydroxy / 17,20-lyase (CYP17) inhibitor (e.g., ketoconazole, abiraterone acetate, galeterone) or next-generation androgen receptor antagonist including apalutamide or enzalutamide. 4. Prior chemotherapy for prostate cancer except if administered in the neoadjuvant or adjuvant setting and last dose \<= 6 months from randomization. 5. Use of 5-alpha reductase inhibitor within 42 days prior to randomization. 6. Use of investigational agents within 28 days prior to randomization. 7. Use of other prohibited medications within seven days prior to Cycle 1 Day 1 on study (see Appendix 3 and 4 for list of prohibited medications). 8. Systemic treatment with a strong Cytochrome P450 3A4 (CYP3A4) inhibitor or a strong cytochromes P450 (CYP450) inducer within 14 days prior to treatment Day 1. 9. Prior bilateral orchiectomy. 10. Uncontrolled hypertension. 11. Baseline severe hepatic impairment (Child-Pugh Class B \& C). 12. An intercurrent illness that is not controlled, such as active infection, psychiatric illness/social situations that would limit compliance with study requirements. 13. Any chronic medical condition requiring a higher dose of corticosteroid than an equivalent of 10 mg prednisone/prednisolone per day. 14. Significant recent bleeding history, as defined as National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade≥2 within three months prior to treatment Day 1, unless precipitated by an inciting event (e.g., surgery, trauma, or injury) 15. Systemic treatment with medications that increase the risk of bleeding, including anticoagulants (warfarin, direct oral anticoagulant, etc.), antiplatelet agents (except for aspirin dosages of ≤ 100mg/day), vascular endothelial growth factor (anti-VEGF) agents, and daily use of COX-1 inhibiting nonsteroidal anti-inflammatory agents (NSAIDs) within 14 days prior to treatment Day 1. 16. Systemic treatment with medications that can prolong the time from the start of the Q wave to the end of the T wave (QT interval) within 14 days prior to treatment Day 1. Shorter washout periods may be permitted with the approval of the principal incestigator, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1. 17. Any history of CTCAE grade ≥2 cardiac conditions within six months before treatment Day 1. Patients with asymptomatic grade 2 non-dysrhythmia cardiovascular conditions may be considered for inclusion, with the approval of the PI, if stable and unlikely to affect patient safety. 18. QT corrected by the Fridericia method (QTcF) prolongation \>450 ms or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia \[defined as serum potassium \<3.0 mEq/L that is persistent and refractory to correction\]), or history of long QT interval syndrome. 19. New York Heart Association Class II, III, or IV congestive heart failure (Appendix 7). 20. Any active gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral medication. 21. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation. 22. Other malignancy within three years prior to treatment Day 1, other than curatively treated basal cell or squamous cell skin or corneal cancer; curatively treated carcinoma in situ of the cervix; or in situ breast carcinoma after complete surgical resection. 23. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection, psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements. 24. Known seropositivity for human immunodeficiency virus. 25. Known active hepatitis A, B, or C virus infection.