Dovitinib (TKI258) and Abiraterone Acetate in Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Dovitinib; Abiraterone Acetate; Prednisone
Intervention description: Starting dose will be 400 mg by mouth daily on Days 1-5, 8-12, 15-19, and 22-26 of each 28 day cycle.; 4 tablets (250 mg each) by mouth daily.; 5 mg by mouth twice daily.
Intervention MeSH terms: Prednisone; Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer; Metastatic Castrate-Resistant Prostate Cancer; mCRPC; Dovitinib; TKI258; Abiraterone Acetate; Zytiga; Prednisone

Summary:

      The goal of this clinical research study is to learn if adding dovitinib to the combination
      of abiraterone acetate and prednisone may help to control metastatic CRPC. The safety of this
      drug combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient or his legally authorized representative must provide written informed
             consent.

          2. Age >/= 18

          3. Eastern Cooperative Oncology Group (ECOG) performance status </= 2

          4. Histologic evidence of prostate adenocarcinoma

          5. Diagnosis of metastatic castration-resistant prostate cancer, with measureable disease
             (lymph nodes and/or visceral metastases by RECIST) or bone metastases.

          6. Patients must have surgical or ongoing chemical castration (with LHRH agonists or LHRH
             antagonists), with a baseline testosterone level < 50ng/dL

          7. Patients must have documented evidence of progressive disease as defined by any of the
             following: a) PSA progression: minimum of 2 rising values (3 measurements) obtained a
             minimum of 7 days apart with the last result being at least >/= 2.0 ng/mL; b) New or
             increasing non-bone disease (RECIST); c) A positive bone scan with 2 or more new
             lesions (PCWG2). Patients must have evidence for metastatic prostate cancer by bone
             scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node). If lymph node, visceral
             and/or soft-tissue metastases are the only evidence of metastasis, at least one lesion
             must be >/= 1.5 cm in diameter.

          8. Laboratory requirements: a) Absolute neutrophil count (ANC) >/= 1,500/ml; b) Platelets
             >/= 100,000/ml; c) Total bilirubin </= 1.5 x upper limit of normal (ULN); d) Serum
             glutamate pyruvate transaminase (SGPT) (ALT) AND/OR Serum glutamate oxaloacetate
             transaminase (SGOT) (AST) </= 3.0 x ULN; e) Creatinine </= 1.5 x ULN; f) White blood
             cell count (WBC) >/= 3,000 uL; g) Hb >/= 8.0 g/dL independent of transfusion

          9. Men whose partner is a woman of childbearing potential must be willing to consent to
             using effective contraception (e.g. male condom with spermicide, diaphragm with
             spermicide, intra-uterine device) while on treatment and for at least 3 months
             thereafter.

         10. Patients may have received prior treatment with androgen ablative therapies (e.g.
             bicalutamide, DES, enzalutamide) and/or "targeted" therapies (such as tyrosine kinase
             inhibitors). Androgen ablative therapies must be discontinued >/=3 days prior to
             initiation of study treatment with the exception of enzalutamide which may be
             continued during protocol treatment per the practice preference of the treating
             physician. Patients who are predicted to benefit from an antiandrogen withdrawal
             response should be tested for this possibility before being considered for eligibility
             to this study. Targeted therapies must be discontinued >/= 2 weeks before initiation
             of study treatment.

         11. Patients may have received up to 2 prior cytotoxic chemotherapy regimens for the
             treatment of metastatic castration-resistant disease, but these therapies must be
             discontinued >/= 3weeks before initiation of study treatment. At least one of the
             regimens must have contained docetaxel and patients must have recovered to < Grade 2
             adverse events from prior chemotherapy or to pretreatment baseline

        Exclusion Criteria:

          1. Patients with histologic evidence of small cell carcinoma of the prostate

          2. Prior therapy with dovitinib or abiraterone acetate or other FGF targeted therapy

          3. Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14
             days

          4. Major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery)
             within 28 days of the date of the first dose of study drugs

          5. Samarium-153 within 28 days of the date of the first dose of study drugs, or
             Strontium-89 within 12 weeks (84 days) of the date of the first dose of study drugs.
             Patients who have received 2 or more doses of bone-seeking radioisotopes are not
             eligible

          6. Current treatment on another therapeutic clinical trial

          7. Impending complication from bone metastases (fracture and/or cord compression).
             Properly treated or stabilized fractures and/or cord compression is allowed

          8. Presence of ongoing urinary obstruction (e.g., urinary retention, hydronephrosis)
             requiring medical intervention. Urinary obstruction relieved with treatment is allowed

          9. Patient has an uncontrolled intercurrent illness (e.g., uncontrolled diabetes,
             uncontrolled hypertension)

         10. Patient has another serious medical or psychiatric illness that could, in the
             investigator's opinion, potentially interfere with the patient's ability to provide
             informed consent or with the completion of treatment according to this protocol

         11. Patients with an active second malignancy that could, in the investigator's opinion,
             potentially interfere with the patient's ability to participate and/or complete this
             trial

         12. Patients with known brain metastases

         13. Impaired cardiac function or clinically significant cardiac diseases, including any of
             the following: a.) History or presence of serious uncontrolled ventricular
             arrhythmias; b. Clinically significant resting bradycardia; c.) Left ventricular
             ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of
             normal (whichever is the higher), or 2-D multiple gated acquisition scan (MUGA) < 45%
             or lower limit of normal (whichever is the higher); d.) Any of the following within 6
             months prior to starting study drug: myocardial infarction (MI), severe/unstable
             angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF),
             Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA);

         14. (Exclusion #14 continued) e.) Chronically uncontrolled hypertension, defined
             conventionally as consistent/repeated systolic pressures above 140 mmHg or diastolic
             pressures above 90 mmHg despite anti-hypertensive therapy. This may be established
             with home BP readings. There is no criterion related to a specific BP result required
             for eligibility, nor are acute BP elevations that are related to iatrogenic causes,
             acute pain, or other transient reversible causes considered an exclusion criterion.
             The intent is to exclude patients with chronically uncontrolled hypertension that
             might be further exacerbated by the study drugs.

         15. Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea,
             vomiting, diarrhea, malabsorption syndrome, or gastric or small bowel resection)

         16. Cirrhosis, chronic active hepatitis or chronic persistent hepatitis

         17. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
             mandatory) or hepatitis B virus (HBV) or hepatitis C virus (HCV) disease or antigen
             positivity

         18. Initiation of bisphosphonate and/or RANKL inhibitors within 4 weeks prior to first
             dose of study drug. Patients already on stable doses of bisphosphonates and/or RANKL
             inhibitors may continue these drugs. However, patients are not allowed to initiate
             bisphosphonate and/or RANKL inhibitors during the study

         19. Any bleeding dyscrasia