A Phase I Study of Dasatinib, Androgen Deprivation Therapy and Radiation For Intermediate and High Risk Prostate Cancer

Inclusion Criteria

PATIENT ELIGIBILITY

-Conditions for Patient Eligibility

Each patient must meet all of the following inclusion criteria to be enrolled in the
study:

- Histologically or pathologically confirmed adenocarcinoma of the prostate to be
treated with radiation therapy and hormone therapy.

- Intermediate, high or very high risk disease

- Intermediate-risk disease (clinical T2b or T2c stage or PSA 10 to 20 ng/mL or
Gleason score 7)

- High-risk disease (Gleason score 8 to 10, serum PSA > 20 ng/mL or T3a disease)

- Very high-risk disease (T3b or T4)

- No prior pelvic or prostate radiation or chemotherapy for prostate cancer.

- Clinically negative lymph nodes as established by imaging (pelvic CT or pelvic MR),
nodal sampling or dissection within 8 weeks prior to registration. Patients with
lymph nodes equivocal or questionable by imaging are eligible if the nodes are < 1.5
cm.

- Bone scan within 12 weeks prior to registration. Equivocal bone scan findings are
allowed if plain films are negative for metastasis.

- ECOG performance status 0-1

- Age > 18

- Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥
1500/µl; platelet count ≥ 100,000/µl; Hgb > 8.0 g/dl; Creatinine < 1.5 x the
institutional ULN, mg/dl; Bilirubin ≤ 2x institutional upper limit of normal; AST ≤
2.5 x upper limit of normal, Serum Na+, K+, Mg2+, Phosphate and Calcium within
institutional normal range; PT and PTT < 1.5 ULN

- Life expectancy of at least 1 year

- No concurrent anticancer therapy.

- Peripheral neuropathy must be ≤ Grade 2

- A male subject of fathering potential must use an adequate method of contraception
throughout the study [and for at least 4 weeks after the last dose of study drug].

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

- Signed study-specific consent form prior to study entry

Conditions for Patient Ineligibility

Patients meeting any of the following exclusion criteria are not to be enrolled in the
study:

- Evidence of distant metastases (M1).

- Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral
orchiectomy for any reason

- PSA > 150

- Pathologically positive lymph nodes or nodes > 1.5 cm on imaging

- Major medical or psychiatric illness which, in the investigator's opinion, would
prevent completion of treatment and would interfere with follow-up.

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable.

- Prior radiotherapy, including brachytherapy, to the region of the study cancer that
would result in overlap of radiation therapy fields

- Medical History and Concurrent Diseases

- No malignancy [other than the one treated in this study] which required radiotherapy
or systemic treatment within the past 5 years.

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

- Pleural or pericardial effusion of any grade

- Cardiac Symptoms; any of the following should be considered for exclusion:

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

- No history of pulmonary hypertension