A Phase 1 Study of Alisertib Participants With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen
Condition: Advanced Solid Tumors; Adenocarcinoma of the Prostate
MeSH terms: Adenocarcinoma
Intervention: Alisertib; Docetaxel
Intervention description: Alisertib ECT; Docetaxel IV infusion
Intervention MeSH terms: Docetaxel
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety and tolerability of alisertib in
      combination with docetaxel as a treatment for participants with advanced solid tumors,
      including castration-resistant prostate cancer, who were deemed by the investigator to be
      medically appropriate candidates for docetaxel therapy.
    

Eligibility criteria:

        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