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Adenocarcinoma of the ProstatePhase 1/2NCT01848067

Alisertib, Abiraterone Acetate and Prednisone in Treating Patients With Hormone-Resistant Prostate Cancer

A Phase 1/2 study testing Alisertib, Abiraterone acetate and Prednisone in people with Adenocarcinoma of the Prostate and Hormone-resistant Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Alisertib, Abiraterone acetate and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
14 Aug 2013to 23 Jun 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Patients must have a pathologically confirmed diagnosis of prostate adenocarcinoma. Features of neuroendocrine phenotype are allowed.
  • Patients must have evidence of metastatic disease.
  • 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.
  • 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).
Show all 20Show fewer
  • 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.
  • Patients must have and ECOG performance status of ≤ 2.
  • Patients must be on continuous LH-RH agonist or antagonist treatment or surgically castrated with castrate levels of testosterone (< 20 ng/dl).
  • 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.
  • For Phase I: Patients must have either failed, are intolerant to, or have refused treatment with docetaxel.
  • For Phase II: Patients must have received 1 but no more than 2 prior chemotherapy regimen for prostate cancer.
  • 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.
  • Patients receiving treatment with bisphosphonates or denosumab must remain on treatment during the study.
  • 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.
  • Patients must have recovered to grade ≤ 1 from all acute toxicity of previous radiation or hormonal or chemotherapy.
  • 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).
  • 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.
  • 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

Who cannot join

  • Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
  • Major surgery within 28 days or serious infection requiring IV antibiotics within 14 days preceding the first dose of study treatment.
  • Patient has received other investigational drugs within 14 days before enrollment.
  • 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.
  • 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)]
  • Ongoing nausea or vomiting of any severity without improvement after appropriate treatment.
Show all 15Show fewer
  • > Grade 1 diarrhea, not controlled with appropriate treatment.
  • 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.
  • 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.
  • Radiation therapy to more than 25% of the active bone marrow. Whole pelvic radiation is considered to be over 25%.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase I/II Study of Alisertib in Combination With Abiraterone and Prednisone for Patients With Castration-Resistant Prostate Cancer After Progression on Abiraterone

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Phase I: To determine the safe dose of alisertib when given in combination with abiraterone (abiraterone acetate) and prednisone in metastatic castration resistant prostate cancer (mCRPC) patients with disease progression on abiraterone and prednisone.
  2. Phase II: To determine the proportion of patients who have no disease progression after alisertib is added to abiraterone and prednisone.

SECONDARY OBJECTIVES:

  1. Phase II: To determine the prostate specific antigen (PSA) kinetics after alisertib is added to abiraterone and prednisone regimen (this includes the proportion of patients with PSA progression free at 3 months, proportion of patients with 50% PSA reduction after study treatment, maximum PSA decline from baseline during the first 12 weeks).
  2. Phase II: To compare baseline circulating tumor cells (CTCs) enumeration to 12 week post-therapy CTC enumeration.
  3. Phase II: To compare baseline neuroendocrine marker (chromogranin A and neuron-specific enolase [NSE]) levels to 12 week post therapy neuroendocrine marker levels.
  4. Phase II: To further assess overall safety of combination of alisertib with abiraterone and prednisone in the phase 1 portion of the study.

OUTLINE: This is a phase I, dose escalation study of alisertib followed by a phase II study.

Patients receive alisertib orally (PO) twice daily (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.

After completion of study treatment, patients are followed up at 30 days.

Being tested
Alisertib, Abiraterone acetate, Prednisone
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlisertibDrug

    Also called MLN8237

    Given PO

  • Abiraterone acetateDrug

    Also called Abiraterone, Zytiga

    Given PO

  • PrednisoneDrug

    Also called Cortan, Deltasone, Orasone, Prednisone Intensol

    Given PO

Study groups in NCT01848067
Study groupRoleWhat they receive
Treatment (alisertib, abiraterone acetate, prednisone)ExperimentalPatients 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.
Receives: Drug: Alisertib; Drug: Abiraterone acetate; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Summarized with descriptive statistics.

    Measured: Up to 21 days

  2. Phase II: Duration of Progression Free Survival According to the PCWG2 Criteria

    The Kaplan-Meier product limit method will be used to estimate the probability distribution of progression free survival (PFS). The proportion of patients achieving at least a 50% decline from baseline will be reported with a 95% confidence interval. The results will be presented graphically using a waterfall plot.

    Measured: 12 weeks

Secondary outcomes (1)

  1. Number of Participants With a PSA Value Equal to or Greater Than 25%

    Compared between the two patient subsets using the nonparametric Mann-Whitney test. A comparison of CTC counts between baseline and at progression for those who have progressed will be carried out using either a paired t test or the nonparameteric Wilcoxon matched pairs test.

    Measured: Baseline up to 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2013 (estimated)
  2. Study start14 Aug 2013
  3. Primary completion3 Mar 2015
  4. Study completion23 Jun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01848067
Sponsor's protocol ID
13P.128
Other IDs
2013-02, JT 2978
Status last verified
May 2025
First submitted
3 May 2013
Last updated
4 May 2025
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 22237781

  • Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. doi: 10.1200/JCO.2007.12.4487.

    PubMed 18309951

  • D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998 Sep 16;280(11):969-74. doi: 10.1001/jama.280.11.969.

    PubMed 9749478

  • Lytton B. Prostate cancer: a brief history and the discovery of hormonal ablation treatment. J Urol. 2001 Jun;165(6 Pt 1):1859-62. No abstract available.

    PubMed 11371867

  • Carroll PR, Kantoff PW, Balk SP, Brown MA, D'amico AV, George DJ, Grossfeld GD, Johnson CS, Kelly WK, Klotz L, Lee WR, Lubeck DP, Mcleod DG, Oh WK, Pollack A, Sartor O, Smith MR, Hart C; Second International Conference on Newer Approaches to Androgen Deprivation Therapy (ADT) in Prostate Cancer. Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):1-6. doi: 10.1016/s0090-4295(02)01559-5. No abstract available.

    PubMed 12231036

  • Denis L, Murphy GP. Overview of phase III trials on combined androgen treatment in patients with metastatic prostate cancer. Cancer. 1993 Dec 15;72(12 Suppl):3888-95. doi: 10.1002/1097-0142(19931215)72:12+3.0.co;2-b. No abstract available.

    PubMed 8252511

  • Hellerstedt BA, Pienta KJ. The current state of hormonal therapy for prostate cancer. CA Cancer J Clin. 2002 May-Jun;52(3):154-79. doi: 10.3322/canjclin.52.3.154.

    PubMed 12018929

  • Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. doi: 10.1056/NEJMoa040720.

    PubMed 15470213

  • de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. doi: 10.1016/S0140-6736(10)61389-X.

    PubMed 20888992

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.

    PubMed 20818862

  • Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94. doi: 10.1200/JCO.2005.04.5252.

    PubMed 16809734

  • de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. doi: 10.1056/NEJMoa1014618.

    PubMed 21612468

  • Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res. 2009 Aug 1;15(15):4792-8. doi: 10.1158/1078-0432.CCR-08-2660. Epub 2009 Jul 28.

    PubMed 19638458

  • Nelson PS. Molecular states underlying androgen receptor activation: a framework for therapeutics targeting androgen signaling in prostate cancer. J Clin Oncol. 2012 Feb 20;30(6):644-6. doi: 10.1200/JCO.2011.39.1300. Epub 2011 Dec 19. No abstract available.

    PubMed 22184375

  • Attard G, Reid AH, Yap TA, Raynaud F, Dowsett M, Settatree S, Barrett M, Parker C, Martins V, Folkerd E, Clark J, Cooper CS, Kaye SB, Dearnaley D, Lee G, de Bono JS. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008 Oct 1;26(28):4563-71. doi: 10.1200/JCO.2007.15.9749. Epub 2008 Jul 21.

    PubMed 18645193

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alisertib, Abiraterone acetate and Prednisone in people with Adenocarcinoma of the Prostate and Hormone-resistant Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01848067, which also lists 52 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.

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