Adenocarcinoma of the Prostate | Alisertib, Abiraterone Acetate and Prednisone in Treating Patients With Hormone-Resistant Prostate Cancer

Adenocarcinoma of the Prostate research study

What is the primary objective of this study?

This phase I/II trial studies the side effects and best dose of alisertib when given together with abiraterone acetate and prednisone and to see how well it works in treating patients with hormone-resistant prostate cancer. Alisertib and abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Androgens can cause the growth of prostate cancer cells. Drugs, such as abiraterone acetate, may also lessen the amount of androgens made by the body. Drugs used in chemotherapy, such as prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving alisertib, abiraterone acetate, and prednisone together may be an effective treatment for prostate cancer.

Who is eligible to participate?

Inclusion Criteria: 1. Age >/= 18 years and are capable of giving informed consent. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 2. Patients must have a pathologically confirmed diagnosis of prostate adenocarcinoma. Features of neuroendocrine phenotype are allowed. 3. Patients must have evidence of metastatic disease. 4. Patients are currently on Abiraterone treatment and the treatment dose has been stable for at least 4 weeks. There will be no further dose adjustment per treating physician. 5. Patients with evidence of any of the following disease progression based on PCWG2 criteria while on abiraterone acetate and prednisone: - Clinical progression (such as symptoms related to prostate cancer) with PSA progression (defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL and a baseline PSA of 2 ng/ml or above). - Progression of one dimension measurable soft tissue (nodal or visceral metastasis) assessed within 30 days prior to registration by a CT scan or MRI of the abdomen and pelvis as per RECIST criteria. - Progression of bone disease (evaluable disease) or ( ≥ 2 new bone lesion(s)) by bone scan. 6. Patients must have and ECOG performance status of ≤ 2. 7. Patients must be on continuous LH-RH agonist or antagonist treatment or surgically castrated with castrate levels of testosterone (< 20 ng/dl). 8. For Phase I: any number of prior chemotherapy regimens are allowed, but patient needs to be on abiraterone acetate at the time of progression. Chemotherapy naïve patients are allowed only in the phase I part of the trial. 9. For Phase I: Patients must have either failed, are intolerant to, or have refused treatment with docetaxel. 10. For Phase II: Patients must have received 1 but no more than 2 prior chemotherapy regimen for prostate cancer. 11. Patients may have had androgen receptor targeted therapy (including second and third line antiandrogens) or other investigational drugs. Patient must have discontinued flutamide or nilutamide or other antiandrogens (including Enzalutamide) for at least 4 weeks and bicalutamide for at least 6 weeks prior to day1 treatment. 12. Patients receiving treatment with bisphosphonates or denosumab must remain on treatment during the study. 13. Patients must not require concurrent radiation or other chemotherapy while receiving protocol therapy. Patients may have received previous radiation but must have completed radiation at least 4weeks (8 weeks for radiation to the brain) prior to registration. 14. Patients must have recovered to grade ≤ 1 from all acute toxicity of previous radiation or hormonal or chemotherapy. 15. Patient agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of Alisertib. Adequate renal function as defined by serum creatinine ≤ 1.5 x ULN. If creatinine >1.5 x ULN, calculated or measured creatinine clearance must be ≥ 40 mL/minute (Cockcroft-Gault). 16. ANC > 1500/mm³, platelets > 100,000/mm³, Hgb > 9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines. 17. Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)< 1.5 x ULN. AST and/or ALT may be up to 5X ULN if with known liver mets Exclusion Criteria: 1. Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection. 2. Major surgery within 28 days or serious infection requiring IV antibiotics within 14 days preceding the first dose of study treatment. 3. Patient has received other investigational drugs within 14 days before enrollment. 4. Known GI disease or GI procedure that could impact drug absorption in the upper bowel, or tolerance of Alisertib. Examples include but are not limited to partial gastrectomy, small bowel resection, pancreatectomy, malabsorption or celiac disease. 5. Patient requires constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed (to manage gastric acidity or reflux) during the study day 8 - 20. [Histamine-2 (H2) receptor antagonists are not permitted from the day prior (Day -1) through to the end of Alisertib dosing (Day 7)] 6. Ongoing nausea or vomiting of any severity without improvement after appropriate treatment. 7. > Grade 1 diarrhea, not controlled with appropriate treatment. 8. History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease requiring supplemental oxygen. 9. Clinical and/or radiographic evidence of cerebral metastases. However, patients who have a history of central nervous system (CNS) metastasis but who have no radiographic or clinical evidence of residual tumor (eg, following complete surgical resection or stereotactic radiosurgery) are not excluded from participation in this study. 10. Radiation therapy to more than 25% of the active bone marrow. Whole pelvic radiation is considered to be over 25%. 11. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. 12. Serious medical or psychiatric illness or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study. 13. Currently active other malignancy excluding controlled non-melanoma skin cancer. Patients are considered NOT to have \"currently active\" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse. 14. Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's Wort within 14 days prior to the first dose of Alisertib and during the study. 15. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Adenocarcinoma of the Prostate

Hormone-resistant Prostate Cancer

Recurrent Prostate Cancer

Stage IV Prostate Cancer

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:AlisertibGiven PO

Drug:Abiraterone acetateGiven PO

Drug:PrednisoneGiven PO

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Treatment (alisertib, abiraterone acetate, prednisone)Patients receive alisertib PO BID on days 1-7, abiraterone acetate PO daily, and prednisone PO BID. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Study Status


Start Date: August 14, 2013

Completed Date: June 23, 2016

Phase: Phase 1/Phase 2

Type: Interventional


Primary Outcome: Phase I: Frequency of Dose Limiting Toxicities of Alisertib, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.1

Secondary Outcome: Number of Participants With a PSA Value Equal to or Greater Than 25%

Study sponsors, principal investigator, and references

Principal Investigator: Jianqing Lin, MD

Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborator: Millennium: The Takeda Oncology Company

More information:

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29. doi: 10.3322/caac.20138. Epub 2012 Jan 4.

Discuss Prednisone