Maximal Androgen Depletion Followed by Randomization of Maximal Androgen Ablation With Molecular Targeted Therapies

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

You are being asked to take part in this study because you have prostate cancer that has spread to other parts of the body.

This is an investigational study. Prednisone is FDA-approved and commercially available. Abiraterone acetate is FDA-approved and commercially available, but is still being researched. Sunitinib malate is FDA-approved for the treatment of gastrointestinal tumors and renal cell carcinoma, and dasatinib is FDA approved and commercially available for certain types of leukemia. The use of these drugs in prostate cancer and in combination with abiraterone acetate and prednisone is investigational.

Up to 180 patients will be enrolled in this study. All will be enrolled at MD Anderson.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborators: Bristol-Myers Squibb; Janssen Scientific Affairs, LLC; Pfizer
• Treatments: Abiraterone Acetate; Androgens; Dasatinib; Prednisone; Sunitinib

Criteria

Inclusion Criteria:

1. Willing and able to provide written informed consent

2. Male aged 18 years and above

3. Histologically or cytologically confirmed adenocarcinoma of the prostate

4. Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT or MRI.

5. Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria

6. Surgically or medically castrated, with testosterone levels ofnM). If the patient is being treated with LHRH agonists (patients who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study.

7. If the patient received previous anti-androgen therapy, then they have shown progression after withdrawal. Patients who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment (>/= 4 weeks since last flutamide, >/= 6 weeks since last bicalutamide or nilutamide). If progression is documented prior to this time interval, patients are eligible.

8. Previous treatment with docetaxel is allowed. Patients must have recovered from any acute toxicity related to the treatment to be eligible.

9. Eastern Cooperative Oncology Group (ECOG) Performance Status of

10. Hemoglobin >/= 9.0 g/dL

11. Platelet count >/= 100,000/microL

12. Serum albumin >/= 3.5 g/dL

13. Serum creatinine/= 60 mL/min

14. Serum potassium >/= 3.5 mmol/L

15. Serum sodium, magnesium, potassium, phosphate, and calcium >/= LLN (lower limit of normal)

16. ANC value >/= 1,000/mm^3

17. Liver function: i. Serum bilirubinGilbert's disease) ii. AST or ALT

18. Able to swallow the study drug whole as a tablet/capsule.

19. Patients who have partners of childbearing potential (.e.g. female that has not been surgically sterilized or who are not amenorrheic for >/= 12 months) must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator during the study and for 13 weeks after last study drug administration.

20. Concomitant Medications (i) Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (at least 5 days prior). (ii) Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia; (iii) Patient agrees to discontinue use of drugs primarily metabolized by CYP3A4 enzyme; (iv) Patient agrees to discontinue use of H2 Inhibitors or proton inhibitors prior to dasatinib administration.

Exclusion Criteria:

1. Active infection (requiring oral or IV antibiotics) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated

2. Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone twice daily.

3. Pathological finding consistent with small cell carcinoma of the prostate

4. Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day 1. Patients who have received palliative radiation to a single site and recovered are eligible.

5. No malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years.)

6. Previously treated with ketoconazole (for prostate cancer) for greater than 7 consecutive days OR previously treated with any other -azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1

7. Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1)

8. Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1)

9. Uncontrolled hypertension (systolic BP >/= 140 mmHg or diastolic BP >/= 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment

10. Prolonged QTc interval on pre-entry electrocardiogram (>/= 450 msec)

11. Active or symptomatic viral hepatitis or chronic liver disease

12. History of pituitary or adrenal dysfunction

13. Known brain metastasis

14. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline

15. History of significant bleeding disorder unrelated to cancer, including: i) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) ii) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) iii) Ongoing or recent (

16. Atrial fibrillation or other cardiac arrhythmia requiring digitalis

17. Other malignancy, except non-melanoma skin cancer, with a >/= 30% probability of recurrence within 24 months

18. Clinically significant pleural effusion as determined by the Principal Investigator.

19. Administration of an investigational therapy for prostate cancer within 30 days of Cycle 1, Day 1

20. Any condition which, in the opinion of the investigator, would preclude participation in this trial.

21. Patients taking category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib) i) quinidine, procainamide, disopyramide ii) amiodarone, sotalol, ibutilide, dofetilide iii) erythromycin, clarithromycin iv) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide v) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

22. Prisoners or subjects who are involuntarily incarcerated.

23. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.