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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
N/A
Open (Enrolling)
Male
Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

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


PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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
therapy

- 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
load

* 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
mm

- 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
dasatinib)

- 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,
lidoflazine

- 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:

Interventional

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:

No

Principal Investigator

Tanya Dorff

Investigator Role:

Principal Investigator

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

4P-12-1

NCT ID:

NCT01685125

Start Date:

September 2012

Completion Date:

September 2016

Related Keywords:

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

Name

Location

USC Norris Comprehensive Cancer CenterLos Angeles, California  90089