A Phase 1 Study of Alisertib Participants With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen

The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested
to treat people who have advanced solid tumors including castration-resistant prostate
cancer.

The study enrolled approximately 41 patients. Participants were enrolled to receive:

• Alisertib 10-40 mg + docetaxel 60-75 mg/m^2

All participants will receive alisertib (ECT) in dose escalating cohorts, orally, twice daily
for 7 days followed by 14-day rest period in Cycle 1, 3 and onwards (21-day cycle) and orally
twice daily from Day 3 to Day 7 followed by 14 day rest period in Cycle 2 [dose held for
pharmacokinetic (PK) collection] along with docetaxel 75 mg/m^2, intravenous (IV) infusion on
Day 1 of each cycle for maximum of 12 months, or until the occurrence of progressive disease
(PD), unmanageable AEs or withdrawal of consent.

This multi-center trial is conducted in United States. The overall time to participate in
this study was until there is evidence of disease progression or unacceptable
treatment-related toxicity. Participants made multiple visits to the clinic, and were
contacted every 12 weeks for up to 25.8 months after last dose of study drug for a follow-up
assessment.

Inclusion Criteria:

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

- 18 years or older

- Histologically or cytologically confirmed advanced tumors and candidates for docetaxel
treatment

- Measurable or evaluable disease is required. Participants must have clinical evidence
of progressive disease or persistent disease

- Participants with castration-resistant prostate cancer (CRPC) are required to have

- Pathologically confirmed adenocarcinoma of the prostate

- Evidence of metastatic disease on bone scan or other imaging. Participants with
prostate-specific antigen (PSA) elevation as the only manifestation of disease
are not eligible.

- Progressive disease after at least 1 hormonal treatment with documented
testosterone levels less than 50 ng/dl

- Concurrent use of an agent for testosterone suppression (e.g., luteinizing
hormone-releasing hormone [LHRH] agonist) is required if the participants 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 participant'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

- Female participants who are postmenopausal for at least 1 year OR are surgically
sterile OR if of childbearing potential, agree to practice 2 effective methods of
contraception at the same time

- Male participants who agree to practice effective barrier contraception during the
entire study and through 6 months after the last dose of study drug 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

Exclusion Criteria:

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

- Female participants who are lactating or pregnant

- Antineoplastic therapy or any experimental therapy within 21 days before the first
dose of alisertib

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

- Concurrent investigational treatment of treatment with any investigational products
within 28 days before the first dose of alisertib

- Radiotherapy to greater than 40% of bone marrow or any radiotherapy (except localized,
small field radiation) within 4 weeks prior to enrollment, unless reviewed and
approved by the medical monitor

- Nitrosoureas or mitomycin-C within 6 weeks before the first dose of alisertib.

- Autologous stem cell transplant within 3 months before the first dose of alisetib, or
prior allogeneic stem cell transplant at any time.

- Use of enzyme-inducing antiepileptic drugs such as phenytoin, carbamazepine or
phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days
prior to the first dose of alisertib

- For CRPC participants:

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

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

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

- Major surgery within 4 weeks of study enrollment

- Uncontrolled high blood pressure

- Participants with abnormal gastric or bowel function or who require continuous
treatment with antacids or proton pump inhibitors

- Participants 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

- 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

- Participants 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

- Prior treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens

- Prior treatment with more than 1 prior taxane-containing regimen