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

• Status: Completed
• Trial end date: 2017-01-04
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Millennium Pharmaceuticals, Inc.
• Treatments: Docetaxel

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