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Dovitinib (TKI258) and Abiraterone Acetate in Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01994590
Recruitment Status : Terminated (Sponsor stopped supplying study drug)
First Posted : November 26, 2013
Results First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Dovitinib Drug: Abiraterone Acetate Drug: Prednisone Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Dovitinib (TKI258) Combined With Abiraterone Acetate in Patients With Metastatic Castrate-Resistant Prostate Cancer Evaluating Markers of FGF and AR Signaling in Bone Marrow and Plasma
Actual Study Start Date : May 19, 2014
Actual Primary Completion Date : June 5, 2017
Actual Study Completion Date : June 5, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dovitinib + Abiraterone Acetate + Prednisone

Participants receive a single daily oral dose of Dovitinib for 5 consecutive days, on Days 1-5, 8-12, 15-19, and 22-26 of each 28 day cycle. Starting dose will be 400 mg daily.

Participant to take 4 tablets (250 mg each) orally (PO) daily of Abiraterone acetate.

Participant to take 5 mg oral prednisone, twice daily.

Drug: Dovitinib
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.
Other Name: TKI258

Drug: Abiraterone Acetate
4 tablets (250 mg each) by mouth daily.
Other Name: Zytiga

Drug: Prednisone
5 mg by mouth twice daily.




Primary Outcome Measures :
  1. Safety and Tolerability [ Time Frame: Participants are followed while actively taking study drug and for at least 30 days post last dose. ]
    Number of Participants with Adverse Events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01994590


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
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Principal Investigator: Paul Corn, MD,PHD M.D. Anderson Cancer Center
  Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01994590    
Other Study ID Numbers: 2013-0086
NCI-2014-00887 ( Registry Identifier: NCI CTRP )
First Posted: November 26, 2013    Key Record Dates
Results First Posted: March 19, 2019
Last Update Posted: March 19, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Prostate Cancer
Metastatic Castrate-Resistant Prostate Cancer
mCRPC
Dovitinib
TKI258
Abiraterone Acetate
Zytiga
Prednisone
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors