Cabazitaxel in Men 75 Years of Age or Older With Castration-Resistant Prostate Cancer

This is a single arm, open label, phase II trial of cabazitaxel every 3 weeks in patients
who are ≥ 75 years of age with castration-resistant, metastatic prostate cancer who have
progressed during or after docetaxel.

Primary objective:

-The primary objective is to determine the efficacy of cabazitaxel in men 75 years of age or
older with castration-resistant, metastatic prostate cancer who have progressed during of
following treatment with docetaxel.

Secondary objectives:

- To characterize the safety and tolerability of cabazitaxel in patients ≥ 75 years of
age

- To determine the PSA response

- To determine the effect of cabazitaxel on functional status using geriatric assessments

Exploratory objectives:

- Determine the effect of therapy with cabazitaxel on the number of circulating tumor
cells (CTC)

- To measure the effects of cabazitaxel on apoptosis in CTCs from patients ≥ 75 years of
age using H2AX and M30 as biomarkers.

- To determine the relationship between geriatric-focused assessment of comorbidity and
functional ability and toxicity and response.

Patients will receive cabazitaxel 25 mg/m2 every 3 weeks with 10 mg prednisone daily until
progression, intolerance of therapy, or withdrawal of consent. Patients will receive
granulocyte colony stimulating factor (Neulasta 6 mg sc) with each cycle, starting with the
first cycle, to minimize the risk of complications from neutropenia. Patients will be
followed for 28 days after discontinuation of therapy or death, whichever occurs first.
Patients with serious adverse events at the time of removal from the trial will be followed
until the toxicities resolve or are deemed irreversible by the treating physician.

Inclusion Criteria:

- Histologically proven, castrate-resistant metastatic prostate cancer without
neuroendocrine differentiation or small cell histology

- Age ≥ 75 years of age

- Progressive disease despite:

- Previous therapy with docetaxel

- Progressive disease for study enrollment is defined by either:

- PSA criteria according to the Prostate Cancer Clinical Trials Working Group (PCWG2)
criteria with a minimum of three rising PSA levels with an interval of ≥ 1 week
between each determination and a PSA at the screening visit of ≥ 2 ng/ml

- Radiographic progression in soft tissue according to Response Evaluation Criteria in
Solid Tumors (RECIST 1.1) criteria

- Appearance of two or more lesions on a bone

- Previous treatment with abiraterone acetate or enzalutamide is allowed, but last dose
must be at least 14 days prior to enrollment in this trial.

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

- Ongoing androgen deprivation with a serum testosterone < 50 ng/dL

- A score of 8-14 on the Mini Nutritional Assessment (MNA) (normal nutritional status
or at risk of malnutrition). MNA in Appendix 4 and available at www.mna-elderly.com.

- Patients must have the following laboratory values:

- Hematologic:

- Absolute Neutrophil Count (ANC) >/=1.5x109/L

- Hemoglobin (Hgb) >/=9 g/dl

- Platelets (plt) >/=100x109/L

- Biochemistry :

- Potassium within normal limits or correctable with supplements

- Total calcium (corrected for serum albumin) and phosphorus within normal limits Liver
and Kidney Functions

- AST (aspartate aminotransferase/glutamic oxaloacetic transaminase/GOT)and ALT
(alanine aminotransferase/glutamic pyruvic transaminase/GPT) ≤ 1.5 x Upper Limit of
Normal (ULN)

- Serum bilirubin
- Serum creatinine clearance will be calculated according to the CKD-EPI (Chronic Kidney Disease
Epidemiology Collaboration) formula and only patients with a creatinine clearance >
60 mL/min will be included.

- Life expectancy of ≥ 6 months

- No concomitant anticancer or investigational drug or participation in an
investigational trial within 30 days of starting treatment with cabazitaxel.
Treatment with nitrosoureas, mitomycin, or monoclonal antibodies, such as
trastuzumab, must be ≥ 6 weeks

- Male participants with partners who are of child bearing potential must agree to use
double barrier method of birth control 28 days prior to study entry, during the study
and for 28 days following the last dose of cabazitaxel OR have history of a
vasectomy.

- Signed informed consent indicating an understanding of the purpose of the study and
the necessary procedures and willingness to participate

Exclusion Criteria:

- History of severe hypersensitivity reaction (≥grade 3) to docetaxel and polysorbate
80 containing drugs

- Uncontrolled severe illness or medical condition (including uncontrolled diabetes
mellitus)

- Concurrent or planned treatment with strong inhibitors or strong inducers of
cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are
already on these treatments)

- Previous treatment with cabazitaxel

- Patients with Central Nervous System (CNS) metastasis. Patients without clinical
signs or symptoms of CNS involvement are not required to have a CT/MRI of the brain

- Clinically significant cardiac disease within 6 months, including myocardial
infarction, New York Heart Association (NYHA) Class III or IV heart disease, or left
ventricular ejection fraction of < 50% at baseline for patients with a history of
congestive heart failure.

- History of another malignancy in the previous 5 years with the exception of
curatively treated non-melanomatous skin cancer.

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness due to potential pharmacokinetic interactions of therapy with
cabazitaxel.

- Other severe acute or chronic medical or psychiatric conditions or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and
in the judgment of the investigator would make the patient inappropriate for entry
into this trial.

- Unresolved toxicities from previous chemotherapy which has not resolved to ≤ grade 1
by CTCAE Version 4.02 criteria with the exception of alopecia or grade 2 peripheral
neuropathy.

- Major surgery ≤ 2 weeks prior to the start of the study or who have not recovered
from a previous surgery. (Placement of a venous access device within 2 weeks is
permitted)