Trial of Dasatinib (Sprycel®) in Subjects With Hormone-refractory Prostate Cancer

NCT00570700 | Completed Phase 2 Results DMC

• 4 other identifiers: UCI 06-602007-5564BMS CA180-097NCI-2010-00336
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this research study is to find out if a new anti-cancer drug, dasatinib (Sprycel®), previously approved for treatment of some forms of leukemia, will be safe and helpful in treating patients with hormone-refractory prostate cancer. This is a research study because the study drug, dasatinib (Sprycel®), has not been evaluated for safety or effectiveness in patients with hormone-refractory prostate cancer. The drug is approved by the Food and Drug Administration for treatment of some forms of leukemia; thus, dasatinib (Sprycel®) is not an investigational drug. It has been given safely to hundreds of patients already. However its safety and usefulness in this study population (prostate cancer) is unknown. Subjects who agree to participate will take 150mg (3 pills) of dasatinib (Sprycel®) daily by mouth for as long as the drug benefits them. During this time, the subject will periodically return to the office for blood/urine tests, X-rays, imaging scans, and/or to complete questionnaires.

Conditions

Hormone-refractory Prostate Cancer; Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Prostate Cancer; Recurrent Prostate Cancer

Keywords

prostate

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Disease Control (DC) (Based on PSA, Bone Scan, FACT-P, RECIST)

  A "positive effect" will be defined as a complete response, partial response, or stable disease. "Lack of positive effect" will be defined as progressive disease. Subjects with a mixed response should be continued on therapy until they either fulfill the criteria for positive effect or lack of positive effect, with evaluation every 56 days. The disease control (DC) rate was evaluated as a composite endpoint of the treatment effect on four parameters: 1) Prostate-specific antigen (PSA), 2) measurable disease (if present) by RECIST criteria, 3) bone scan, and 4) quality-of-life as measured by the FACT-P questionnaire.

  From day 56 (8 weeks) and every 8 weeks thereafter until the date of first documented progression or date of death from any cause, whichever came first, assessed until death, the patient withdraws consent, or the study ends, up to 2 years

Secondary Outcomes (2)

• Time to Prostate-specific Antigen (PSA) Progression

  From initial date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• Number of Subjects With Dasatinib Toxicity Using Common Terminology Criteria (CTC) (v. 3.0)

  From initial date of treatment through study completion, up to 2 years

Study Arms (1)

Dasatinib

EXPERIMENTAL

Patients receive oral dasatinib once daily in the absence of disease progression or unacceptable toxicity.

Drug: Dasatinib

Interventions

Dasatinib DRUG

150mg (3 pills) orally daily for as long as the drug benefits

Also known as: Sprycel®, BMS-354825

Dasatinib

Eligibility Criteria

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

You may qualify if:

• Must have biopsy-proven adenocarcinoma of the prostate
• Must have hormone-refractory prostate cancer, defined as an increasing PSA by \>= 3 ng/ml from androgen-blockade nadir, or new measurable or evaluable lesion on imaging studies, after treatment with orchiectomy, luteinizing hormone-releasing hormone (LHRH) agonist, antiandrogen or diethylstilbestrol (DES)
• Subjects must have received at least one cycle of single-agent or combination chemotherapy for hormone refractory prostate cancer (HRPC), last administered at least 4 weeks prior to the start of dasatinib
• Subjects may not have received more than one type (single agent or combination) of chemotherapy regimen; subjects may include (but are not limited to) the following: HRPC subjects who were treated with palliative chemotherapy and either failed to respond, or responded for a period of time but now have worsening disease (i.e. relapsed/refractory to chemotherapy); HRPC subjects who were treated with palliative chemotherapy but stopped treatment because of toxicity (i.e. intolerant of chemotherapy); HRPC subjects who have been treated with palliative chemotherapy with response, whose chemotherapy has been interrupted, and who now have evidence of progressive disease (i.e. potentially chemotherapy responsive but subject does not desire to restart cytotoxic drugs)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of at least 8 weeks, based on clinical judgment of the treating physician
• Adequate hematologic, renal and liver function as evidenced by the following (subjects may have lower hematologic parameters if the cytopenias are thought by the treating physician to be secondary to marrow involvement by prostate cancer):
• white blood cell count (WBC) \> 2.0 bil/L; grade 0-1
• absolute neutrophil count (ANC) \> 1.0 bil/L; grade 0-1
• Platelets \> 100 bil/L; grade 0-1
• Hemoglobin \> 8.0gm/dL
• Creatinine \< 1.5x upper limit of normal (ULN)
• Prothrombin time (PT), Partial Thromboplastin Time (PTT) \< 1.2 x ULN; grade 0-1
• Total bilirubin \< 2x ULN
• aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 2.5x ULN

You may not qualify if:

• Subjects should have had no chemotherapy within 4 weeks of the start of treatment with dasatinib
• Prior localized radiotherapy for metastatic disease is permitted, provided the treatment volume is less than25% of potential marrow space (the radiotherapy must have been completed 6 weeks prior to enrollment)
• Systemic radiotherapy with samarium-153 must have been completed at least 2 months prior to enrollment (subjects may not have received prior strontium-89 \[Metastron\] therapy)
• At least 6 weeks have elapsed from the last dose of cytotoxic or targeted therapeutics to the time of prescreening; if the subject has received a combination regimen of standard chemotherapy plus an investigational agent, a 6 week washout period is required
• Subjects may not have received treatment with any kinase inhibitor
• At least 2 months must have elapsed from time of dosing with vaccines to the time of prescreening
• No malignancy, other than prostate cancer, that required radiotherapy or systemic treatment within the past 5 years
• Subjects may not have any of the following: Clinical evidence of uncontrolled heart failure, myocardial infarction, or angina within the previous 6 months; prolonged QT interval Fridericia's (QTcF) \> 450msec; history of unstable ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation, or torsades de pointes); concomitant use of drugs known to cause torsades de pointes \[quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine,thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine\] (these agents must have been discontinued at least 7 days prior to starting dasatinib); subjects with hypokalemia or hypomagnesemia are excluded if the electrolyte anomaly cannot be corrected
• Subjects may not be enrolled with any of the following: History of a significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); GI bleeding from any cause within 3 months; Concomitant use of anticoagulants, except for low-dose warfarin (for prophylaxis to prevent catheter thrombosis) or heparin flushes (for IV lines), is prohibited (Note that chronic use of aspirin is prohibited)
• Subjects must meet the following restrictions: Subjects may not have a concurrent medical condition which may increase the risk of toxicity, including pleural or pericardial effusion of any grade, or uncontrolled hypertension; Concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended (The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy); Patient must discontinue St. Johns Wort while receiving dasatinib therapy; Subjects must not use intravenous bisphosphonates during the first 8 weeks of dasatinib therapy due to risk of hypocalcemia; Subjects may not be receiving any restricted cytochrome P450 3A4 (CYP3A4) inhibitors (If the investigator feels that any of these agents should be given as uniquely useful for a clear diagnosis, the situation should be discussed with the Principal Investigator, and a clear monitoring program should be planned)
• Subjects may not have evidence of untreated intracranial metastases, or untreated prostate cancer producing spinal cord compression

Sponsors & Collaborators

• University of California, Irvine: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Loma Linda University Cancer Center

Loma Linda, California, 92354, United States

Location

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

St. Joseph Hospital

Orange, California, 92868, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina, and Hollings Cancer Network

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Twardowski PW, Beumer JH, Chen CS, Kraft AS, Chatta GS, Mitsuhashi M, Ye W, Christner SM, Lilly MB. A phase II trial of dasatinib in patients with metastatic castration-resistant prostate cancer treated previously with chemotherapy. Anticancer Drugs. 2013 Aug;24(7):743-53. doi: 10.1097/CAD.0b013e328361feb0.

  PMID: 23652277 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Dasatinib

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)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: UC Irvine Health / Chao Family Comprehensive Cancer Center
• Organization: UC Irvine Health / Chao Family Comprehensive Cancer Center

ucstudy@uci.edu

1-877-UC-STUDY

Study Officials

• Michael B Lilly, MD, FACP

  Chao Family Comprehensive 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: PRINCIPAL INVESTIGATOR
• PI Title: Cancer Center

Study Record Dates

• First Submitted: December 6, 2007
• First Posted: December 11, 2007
• Study Start: July 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: February 26, 2019
• Results First Posted: May 25, 2018

Record last verified: 2019-02

Locations

US (6)