Trial of Dasatinib (Sprycel®) in Subjects With Hormone-refractory Prostate Cancer
|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: NCT00570700|
Recruitment Status : Completed
First Posted : December 11, 2007
Results First Posted : May 25, 2018
Last Update Posted : May 25, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Hormone-refractory Prostate Cancer Adenocarcinoma of the Prostate Hormone-resistant Prostate Cancer Prostate Cancer Recurrent Prostate Cancer||Drug: Dasatinib||Phase 2|
Metastatic prostate adenocarcinoma is initially dependent on exogenous androgens for survival and growth; hence, androgen blockade is a key initial intervention for these patients. Whether by orchiectomy or by biochemical blockade, androgen deprivation produces objective regression of prostate cancer in >90% of patients for an average of 1.5-2yrs. Afterwards, however, the remaining prostate cancer cells become independent of exogenous androgen and resume their growth. At this stage the disease is referred to as hormone-refractory prostate cancer (HRPC).
Treatment for HRPC remains unsatisfactory. Only two interventions have been proven through randomized, prospective studies to confer a survival advantage. Docetaxel administered along with prednisone or estramsutine increases overall survival by approximately 3 months, compared with patients treated with mitoxantrone (1,2). In addition, a cell-based vaccine (APC8015) has recently been shown to confer a similar survival advantage for patients with HRPC (3). In 127 patients with HRPC randomized to receive the APC8015 vaccine or unactivated autologous peripheral blood mononuclear cells, there was a 4.5-month increase in median overall survival for the treated cohort (p = 0.01). Thus additional therapeutic tools are needed.
Although the mechanisms whereby androgen-independence develops are not yet fully clarified (7), it is known that malignant progression of prostate cancer involves upregulation of autocrine growth factors and their receptors (8). The process of autocrine reprogramming facilitates autonomous growth and metastasis of the tumor cells. For this reason many of the major novel therapeutic approaches for prostate cancer, currently in clinical trials, are directed against growth factor signaling pathways involving tyrosine kinase receptors and their downstream signaling messengers. Among these, recent evidence suggests a centrol role for the non-receptor tyrosine kinase c-src, in the development, growth, and metastasis of many human cancers (9,10), including prostate carcinomas. Several SFKs are present in prostate cancer cells, including c-src, yes, lck, and lyn (11). SFKs are thought to mediate the signaling pathways of several growth factors and stressors, such as lysophosphatidic acid, bombesin, androgens, and hypoxia (12-15). In prostate cancer cells that are androgen-independent, activation of SFKs is constitutive, rather than ligand-regulated (16). SFKs in turn regulate such diverse prostate cell pathways as VEGF production (15), and FAK signaling (17). Among the response phenotypes mediated by SFKs include cell spreading and attachment, migration and invasion. Genetic and pharmacologic inhibitors of SFKs have been tested on prostate cancer cell lines. Thus two pyrrolopyrimidine c-src inhibitors were shown to inhibit production of the protease MMP-9, as well as the functional ability of the cells to invade Matrigel (18). These phenotypes occurred at inhibitor concentrations that did not significantly affect cell proliferation. In contrast a peptide inhibitor of the lyn kinase inhibited the proliferation of prostate cancer cell lines in culture, and reduced the growth of DU145 xenografts in nude mice (19). Thus a spectrum of responses have been seen in prostate cancer cells or tumors treated with SFK inhibitors, including inhibition of growth.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||BMS CA180-097: A Phase II Trial of Dasatinib (Sprycel®) in Subjects With Hormone-refractory Prostate Cancer, Previously Treated With Chemotherapy|
|Study Start Date :||July 2007|
|Actual Primary Completion Date :||February 2012|
|Actual Study Completion Date :||February 2012|
Patients receive oral dasatinib once daily in the absence of disease progression or unacceptable toxicity.
150mg (3 pills) orally daily for as long as the drug benefits
- Number of Subjects With Disease Control (DC) (Based on PSA, Bone Scan, FACT-P, RECIST) [ Time Frame: 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 ]
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.
- Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: 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 ]Time to PSA progression, defined as the interval from the first day of dasatinib treatment until either (1) there has been a 50% increase in PSA above the treatment nadir, with a minimum of 5ng/mL, or (2) a 25% increase in PSA level above pretreatment levels, with a minimum of 5ng/mL. All PSA-based assessments require a confirmatory level no more than 1 month later.
- Number of Subjects With Dasatinib Toxicity Using Common Terminology Criteria (CTC) (v. 3.0) [ Time Frame: From initial date of treatment through study completion, up to 2 years ]Due to relatively poor drug tolerance and relatively rapid PSA increases in most patients it was not feasible to continue patients on treatment until there was radiographic evidence of disease progression.
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): NCT00570700
|United States, California|
|City of Hope National Medical Center|
|Duarte, California, United States, 91010|
|Loma Linda University Cancer Center|
|Loma Linda, California, United States, 92354|
|Chao Family Comprehensive Cancer Center|
|Orange, California, United States, 92868|
|St. Joseph Hospital|
|Orange, California, United States, 92868|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, South Carolina|
|Medical University of South Carolina, and Hollings Cancer Network|
|Charleston, South Carolina, United States, 29425|
|Principal Investigator:||Michael B Lilly, MD, FACP||Chao Family Comprehensive Cancer Center|