Clinical Trial Detail

This is a randomized, open-label, multicenter, Phase 2, two-arm study that will evaluate the efficacy and safety of MLN8237 given orally in combination with docetaxel and prednisone as a treatment for castration-resistant prostate cancer (CRPC). It will be preceded by a Phase 1 portion to determine tolerable doses and schedules of MLN8237 and docetaxel to be evaluated in the Phase 2 portion.

Genders Eligible for Study: Male

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

- Males 18 years or older

- Pathologically confirmed adenocarcinoma of the prostate

- PSA > 5 ng/mL or radiographically measurable disease

- Evidence of metastatic disease on bone scan or other imaging

- Progressive disease after at least 1 hormonal treatment

- Concurrent use of an agent for testosterone suppression is required if the patient has not been surgically castrated

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Recovered to less than or equal to Grade 1 toxicity (CTCAE), to patient's baseline status (except alopecia) or deemed irreversible from the effects of prior cancer therapy and must have evidence of progressive or persistent disease

- Adequate bone marrow, liver and renal function

- Any use of opiates must be stable for at least 2 weeks prior to study entry

- Patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse

- Voluntary written consent

- Willing to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

- Suitable venous access for blood sampling

Other eligibility criteria may apply.

- Prior treatment with antineoplastic chemotherapy or radioisotopes for metastatic prostate cancer

- Prior or current investigational therapies within 4 weeks before the first dose of MLN8237

- Radiotherapy or antiandrogen therapy for prostate cancer within 4 weeks prior to enrollment

- Use of products known to affect PSA levels within 4 weeks of enrollment

- Radiotherapy to greater than 25% of bone marrow

- Localized radiation within 4 weeks of enrollment

- Compromised bone marrow including patients with a superscan result on a bone scan

- Major surgery within 4 weeks of study enrollment

- Uncontrolled high blood pressure

- Patients receiving chronic steroid therapy other than the following: low dose steroid for the control of nausea and vomiting, topical steroid, inhaled steroid or use of dexamethasone

- Known severe hypersensitivity to docetaxel or other drugs formulated in polysorbate 80

- Comorbid condition or unresolved toxicity that would preclude administration of docetaxel and prednisone

- Medical contraindication to any of the docetaxel pre-medications

- Prior history of Grade 2 or greater neurotoxicity or any toxicity that has not resolved to Grade 1 or below

- Symptomatic brain or other CNS metastasis

- Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected

- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

- Patients requiring full systemic anticoagulation

- Prior allogeneic bone marrow or other organ transplant

- Active infection requiring systemic therapy within 14 days preceding first dose, or other serious infection

- History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months

- Serious medical or psychiatric illness that could interfere with protocol completion

- Inability to swallow oral medication

- Uncontrolled pain at baseline, impending complication from bone metastasis and/or presence of urinary obstruction

Other exclusion criteria may apply.