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A Randomized Phase II Trial of Dasatinib Plus Abiraterone Compared to Abiraterone Alone for Metastatic, Castration-Resistant Prostate Cancer Prior to Chemotherapy

Phase 2
18 Years
Open (Enrolling)
Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

Thank you

Trial Information

A Randomized Phase II Trial of Dasatinib Plus Abiraterone Compared to Abiraterone Alone for Metastatic, Castration-Resistant Prostate Cancer Prior to Chemotherapy


I. To compare the progression-free survival of men with metastatic castration-resistant
prostate cancer treated with abiraterone (abiraterone acetate) plus dasatinib to that of men
treated with abiraterone alone.


I. To describe the toxicity profile of the combination, as well as the rate of
prostate-specific antigen (PSA) response, objective responses, and changes in circulating
tumor cell (CTC) numbers.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive
abiraterone acetate 1000 mg orally (PO) once daily (QD) and prednisone 5 mg PO twice daily
(BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or
unacceptable toxicity.

ARM B: Patients receive abiraterone acetate and prednisone as patients in arm A. Patients
also receive dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Metastatic, castration-resistant prostate cancer

- Defined as evaluable radiographic disease with rising PSA x 2 (at least 1 week
apart) or radiographic progression (new soft tissue/bone lesions or enlarging
soft tissue lesions) despite medical or surgical castration

- No limit on prior hormonal therapies (i.e. anti-androgens, ketoconazole) except
that subject must not have received abiraterone previously

- No limit on prior biologic therapies (i.e. immune therapy, antiangiogenic,
targeted) except that patient should not have received dasatinib or other v-src
sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (src)-targeted

- No prior chemotherapy for metastatic disease

* Subjects who have received chemotherapy in the neoadjuvant or adjuvant setting will
be eligible provided chemotherapy was completed > 6 months prior to enrollment

- Eastern Cooperative Oncology Group (ECOG) 0-2

- Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) except for
Gilbert's syndrome

- Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] )
=< 2.5 times the institutional ULN

- Serum sodium (Na), potassium (K+), magnesium (Mg+), phosphate and calcium (Ca+) >
lower limit of normal (LLN)

- Serum creatinine =< 1.5 time the institutional ULN

- Hemoglobin (Hb) >= 9

- Platelets >= 100,000

- Absolute neutrophil count (ANC) >= 1000

- Ability to take oral medication (study medications must be swallowed whole)

- Men with fathering potential must agree to use contraception throughout study
treatment; acceptable methods include: condoms, sponge, intrauterine device (IUD),
oral contraceptives

- Concomitant medications * Patient agrees to discontinue St. Johns wort while
receiving dasatinib therapy (discontinue St. Johns wort at least 5 days before
starting dasatinib)

Exclusion Criteria:

- Known hepatitis B or C or human immunodeficiency virus (HIV), regardless of viral

* Testing for the purposes of enrollment is not mandatory, however a documented
history of these infections will be exclusionary due to concerns for drug-drug
interactions with antivirals and potential for increased risk of liver toxicity

- Radiation for palliation of bony metastases within the preceding 2 weeks

- Prior chemotherapy for metastatic castration-resistant prostate cancer (CRPC)

* Immune therapy with sipuleucel-T is allowed, provided the last infusion was >= 28
days prior to study therapy and there has been at least one documented PSA value
rising after completion of sipuleucel-T therapy or progression of disease on imaging
after sipuleucel-T

- Malignancy (aside from prostate cancer) which required radiotherapy or systemic
treatment within the past 5 years

- Superficial bladder cancer treated with intravesical therapy and currently in
remission will not be an exclusion

- Skin cancers will not be an exclusion, except for melanoma with a thickness > 1

- Concurrent medical condition which may increase the risk of toxicity, including:

- Pleural or pericardial effusion of any grade at the time of study entry

- Cardiac symptoms; any of the following should be considered for exclusion: **
Uncontrolled angina, congestive heart failure or myocardial infarction (MI)
within (6 months)

- Diagnosed congenital long QT syndrome

- Any history of clinically significant ventricular arrhythmias (such as
ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
** Prolonged QTc/f interval on pre-entry electrocardiogram (> 450 msec)

- Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior
to abiraterone administration

- History of significant bleeding disorder unrelated to cancer, including:

- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
VIII antibodies)

- Ongoing or recent (=< 3 months) significant gastrointestinal bleeding

- Prohibited treatments and/or therapies

- Subjects should not be on any additional anti-cancer therapy except for
luteinizing hormone-releasing hormone (LHRH) agonist/antagonist; specifically
excluded medications include ketoconazole, estrogens, and anti-androgens

- Category I drugs that are generally accepted to have a risk of causing Torsades
de pointes including: (Patients must discontinue drug 7 days prior to starting

- Quinidine, procainamide, disopyramide

- Amiodarone, sotalol, ibutilide, dofetilide

- Erythromycin, clarithromycin

- Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

- Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine,
domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin,

- Prisoners or subjects who are involuntarily incarcerated

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome Description:

PFS defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A one-sided, 0.05-level log rank test will be used to compare the two arms in terms of PFS. PFS will be estimated using the product-limit method of Kaplan and Meier.

Outcome Time Frame:

From the start of abiraterone acetate until first evidence of disease progression or until death from any cause, whichever occurs first, assessed up to 3 years

Safety Issue:


Principal Investigator

Tanya Dorff

Investigator Role:

Principal Investigator

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

September 2012

Completion Date:

September 2016

Related Keywords:

  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Prostatic Neoplasms



USC Norris Comprehensive Cancer Center Los Angeles, California  90089