Clinical Trials /

Pacritinib for Biochemical Relapse After Definitive Treatment for Prostate Cancer

NCT04635059

Description:

This is a single-arm, open-label study using pacritinib for patients with histologically confirmed prostate adenocarcinoma, status post definitive treatment and biochemical recurrence.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pacritinib for Biochemical Relapse After Definitive Treatment for Prostate Cancer
  • Official Title: Pacritinib for Biochemical Relapse After Definitive Treatment for Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: IIT-KILARI-J31001-BLAST
  • NCT ID: NCT04635059

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
PacritinibSB1518Pacritinib

Purpose

This is a single-arm, open-label study using pacritinib for patients with histologically confirmed prostate adenocarcinoma, status post definitive treatment and biochemical recurrence.

Detailed Description

      This phase 2, single-arm, open-label study using pacritinib will treat patients with
      histologically confirmed prostate adenocarcinoma, status post definitive treatment and
      biochemical recurrence.

      The primary objective of this study is to determine the effect of pacritinib on the time to
      prostate-specific antigen (PSA) progression in patients with biochemical relapse of prostate
      cancer (defined as the length of time that a given subject will be alive and free from PSA
      progression per Prostate Cancer Working Group 3 (PCWG3) guidelines.
    

Trial Arms

NameTypeDescriptionInterventions
PacritinibExperimentalPacritinib is an oral drug.
  • Pacritinib

Eligibility Criteria

        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 ≤ 12 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 (Appendix 3
             and Appendix 4, respectively)

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of patients with six-month PSA progression-free survival.
Time Frame:Six months
Safety Issue:
Description:PSA progression-free survival is defined as the length of time that a subject will be alive and free from PSA progression per PCWG3 guidelines.

Secondary Outcome Measures

Measure:PSA Levels
Time Frame:Screening, every month for six months, then every two months until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.
Safety Issue:
Description:PSA level in blood is measured in units of nanograms per milliliter.
Measure:Testosterone Measurement
Time Frame:Baseline and four months
Safety Issue:
Description:Serum testosterone will be measured in nanograms per deciliter.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Medical College of Wisconsin

Last Updated

November 18, 2020