Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

PRIMARY OBJECTIVES:

I. To evaluate the impact of octreotide in reducing the incidence of grade 2 or greater
diarrhea in men receiving cabazitaxel plus prednisone for castration-resistant prostate
cancer (CRPC) after docetaxel therapy.

SECONDARY OBJECTIVES:

I. Overall survival (OS).

II. Progression-free survival (PFS) (defined as the time between treatment start and the
first date of progression as measured by objective tumor progression using the Response
Evaluation Criteria In Solid Tumors (RECIST), pain progression or death).

III. Prostate-specific antigen (PSA) response rate.

IV. Objective response rate.

V. Pain response.

VI. Toxicity.

OUTLINE:

Patients receive cabazitaxel as intravenous (IV) infusion over 1 hour on day 1, prednisone
by mouth (PO) every day (QD), and octreotide pamoate given as intramuscular (IM) injection
on day 1. Patients also receive octreotide acetate as a subcutaneous (SC) injection three
times a day (TID) on days 1-14 of course 1 only. Treatment with cabazitaxel repeats every 21
days and treatment with prednisone and octreotide pamoate repeats every 4 weeks for up to 10
courses in the absence of disease progression or unacceptable toxicity. After completion
of study treatment, patients are followed up at 1 month, every 3 months until disease
progression, and then every 6 months thereafter.

Inclusion Criteria:

- Histologically or cytologically confirmed prostate cancer

- Measurable disease on computed tomography (CT) or evaluable disease with an elevated
PSA

- Documented progression on (a) at least one prior hormone treatment, which must have
incorporated luteinizing hormone-releasing hormone (LHRH) agonist therapy AND (b) at
least one chemotherapy regimen, which must have included docetaxel; progression may
be demonstrated by radiologic criteria or by PSA only if accompanied by new or
worsening symptoms (pain progression)

- Eastern Cooperative Oncology Group (ECOG) performance score of 0-2

- Absolute neutrophil count (ANC) more than or equal to 1500/ul

- Hemoglobin more than or equal to 8.0 g/dL

- Platelet count more than or equal to 100,000/ul

- Serum creatinine less than or equal to 1.5x the upper limit of normal (ULN)

- Bilirubin less than or equal to ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
equal to 1.5x ULN

- Must be recovered from acute and late effects of any prior surgery, radiotherapy or
other anti-neoplastic therapy

- Patients or their legal representatives must be able to read, understand, and provide
informed consent

- Men of childbearing potential must consent to use barrier contraception while on
treatment and for 90 days thereafter

- Palliative radiation for metastatic disease is allowed if less or equal to 40% of the
total bone marrow was irradiated; 28 days must have elapsed since completion of
radiation therapy (RT) with bone marrow recovery; soft tissue disease irradiated in
the prior 2 months may not be designated as measurable disease

- Concomitant bisphosphonate use is permitted if the dose had been stable for 12 weeks
prior to enrollment

Exclusion Criteria:

- Treatment with radiotherapy, chemotherapy or any investigational agent in the prior 4
weeks

- Major surgery in the prior 4 weeks

- Prior treatment with cabazitaxel

- Patients with known hypersensitivity to cabazitaxel, other drugs formulated with
polysorbate 80 or octreotide

- Inability to tolerate oral prednisone

- Grade 2 or greater diarrhea in the prior 2 weeks

- Grade 2 or greater neuropathy or stomatitis

- Presence of an active uncontrolled infection or fever greater or equal to 38.5
degrees

- Presence of parenchymal brain metastases; patients with neurological symptoms must
have a CT or magnetic resonance imaging (MRI) of the brain showing no metastases
within 60 days of enrollment

- Prior malignancy within the past 5 years with the exception of curatively treated
basal cell or squamous cell carcinoma of the skin or superficial bladder or other
stage I or stage II cancer in complete remission for at least 12 months

- History of unstable or newly diagnosed angina pectoris, documented history of current
serious arrhythmia or congestive heart failure (CHF) or recent myocardial infarction
(MI)within 6 months of enrollment

- Known human immunodeficiency virus (HIV) or hepatitis infection

- Life expectancy less than 3 months

- Presence of any other medical condition, including mental illness or substance abuse,
deemed by the investigator to be likely to interfere with a patient's ability to sign
informed consent, cooperate and participate in the study, or interfere with
interpretation of the results

- Lack of ability/willingness to give informed consent

- Lack of ability/willingness to receive octreotide injection

- Anticipated non-availability for study visits/procedures

- Patients with uncontrolled diabetes, defined as a HbA1c greater than 7% or greater or
equal to 8% despite therapy, or a fasting plasma glucose more than 2x ULN; at the
investigator's discretion, non-eligible patients can be re-screened after adequate
medical therapy has been instituted