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

NCT01994590 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2013-0086NCI-2014-00887
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Metastatic Castrate-Resistant Prostate Cancer; mCRPC; Dovitinib; TKI258; Abiraterone Acetate; Zytiga; Prednisone

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  Number of Participants with Adverse Events

  Participants are followed while actively taking study drug and for at least 30 days post last dose.

Study Arms (1)

Dovitinib + Abiraterone Acetate + Prednisone

EXPERIMENTAL

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; Drug: Abiraterone Acetate; Drug: Prednisone

Interventions

Dovitinib DRUG

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.

Also known as: TKI258

Dovitinib + Abiraterone Acetate + Prednisone

Abiraterone Acetate DRUG

4 tablets (250 mg each) by mouth daily.

Also known as: Zytiga

Dovitinib + Abiraterone Acetate + Prednisone

Prednisone DRUG

5 mg by mouth twice daily.

Dovitinib + Abiraterone Acetate + Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient or his legally authorized representative must provide written informed consent.
• Age \>/= 18
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2
• Histologic evidence of prostate adenocarcinoma
• Diagnosis of metastatic castration-resistant prostate cancer, with measureable disease (lymph nodes and/or visceral metastases by RECIST) or bone metastases.
• Patients must have surgical or ongoing chemical castration (with LHRH agonists or LHRH antagonists), with a baseline testosterone level \< 50ng/dL
• 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.
• 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
• 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.
• 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.
• 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

You may not qualify if:

• Patients with histologic evidence of small cell carcinoma of the prostate
• Prior therapy with dovitinib or abiraterone acetate or other FGF targeted therapy
• Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days
• Major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose of study drugs
• 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
• Current treatment on another therapeutic clinical trial
• Impending complication from bone metastases (fracture and/or cord compression). Properly treated or stabilized fractures and/or cord compression is allowed
• Presence of ongoing urinary obstruction (e.g., urinary retention, hydronephrosis) requiring medical intervention. Urinary obstruction relieved with treatment is allowed
• Patient has an uncontrolled intercurrent illness (e.g., uncontrolled diabetes, uncontrolled hypertension)
• 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
• 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
• Patients with known brain metastases
• 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);
• 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)
• Cirrhosis, chronic active hepatitis or chronic persistent hepatitis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Corn,Paul,M.D. Ph.D. / Genitourinary Medical Oncology
• Organization: UT MD Anderson Cancer Center

PCorn@mdanderson.org

713-792-2830

Study Officials

• Paul Corn, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2013
• First Posted: November 26, 2013
• Study Start: May 19, 2014
• Primary Completion: June 5, 2017
• Study Completion: June 5, 2017
• Last Updated: March 19, 2019
• Results First Posted: March 19, 2019

Record last verified: 2019-02

Locations

US (1)