Small Cell Prostate CancerPhase 2NCT01799278
A Phase II Trial of MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer
A Phase 2 study testing MLN8237 in people with Small Cell Prostate Cancer and Neuroendocrine Prostate Cancer, run by Weill Medical College of Cornell University at 8 sites in United States.
Trial summary
This study will evaluate the response rate of MLN8237 in patients with histologically confirmed or clinically suspected metastatic neuroendocrine prostate cancer (NEPC). MLN8237 is an orally administered Aurora kinase A inhibitor that has demonstrated broad antitumor activity in vitro and in vivo. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Small Cell Prostate Cancer, Neuroendocrine Prostate Cancer, Prostate Adenocarcinoma Plus > 50% Immunohistochemical Staining for Neuroendocrine Markers
- What is being tested?
- MLN8237
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 8 sitesUnited States
- Study dates
- Feb 2013to Aug 2017
- Phase
- Phase 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
- Metastatic prostate carcinoma and at least one of the following:
- Histologic diagnosis of small cell or neuroendocrine prostate cancer
- Histologic diagnosis of prostate adenocarcinoma plus > 50% immunohistochemical staining for neuroendocrine markers (chromogranin, synaptophysin or neuron specific enolase)
- Development of liver metastases in the absence of PSA progression as defined by PCWG2
- Serum chromogranin A level >5 x upper limit of normal and/or serum neuron specific enolase (NSE) >2x upper limit of normal
- Measurable disease by RECIST 1.1 with PCWG2 modifications
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- Patients with pure small cell neuroendocrine carcinoma on histology are not required to have received prior androgen deprivation therapy (ADT) or castrate levels of testosterone, but their testosterone state should be maintained for the duration of the study. Other patients are required to have surgical or ongoing chemical castration, with baseline testosterone level <50ng/dL.
- Patients capable of fathering children must agree to use an effective method of contraception for the duration of the trial and should continue use for 4 months after last dose of study drug
- Subjects must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration.
- 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 metastases provided bilirubin is normal.
- 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).
- ECOG performance status 0-2
- Estimated life expectancy > 3 months
- 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.
Who cannot join
- Radiation therapy to 25% of bone marrow within 2 weeks of first dose
- Residual > Grade 2 toxicity from prior treatment must have resolved with the exception of those explicitly described elsewhere in entry criteria
- Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
- Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed (see section 5.5)
- Severe or uncontrolled systemic infection
- 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.
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- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, 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 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 MLN8237 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
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Chicago
Chicago, Illinois, 60637
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke University Health System
Durham, North Carolina, 27710
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Weill Cornell Medical College
New York, New York, 10065
University of Washington Medical Center
Seattle, Washington, 98195
About this study
Official title: A Phase II Trial of the Aurora Kinase A Inhibitor MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer
This study will evaluate the response rate of MLN8237 in patients with histologically confirmed or clinically suspected metastatic neuroendocrine prostate cancer (NEPC). MLN8237 is an orally administered Aurora kinase A inhibitor that has demonstrated broad antitumor activity in vitro and in vivo. In preclinical models, aurora kinase inhibition resulted in dramatic and preferential anti-tumor activity in NEPC with suppression of neuroendocrine marker expression.
Read the detailed description
This is a multi-institutional single-arm, open-label Phase 2 trial evaluating MLN8237 in patients with histologically confirmed or clinically suspected metastatic neuroendocrine prostate cancer. Subjects will be treated with MLN8237 at 50 mg twice daily for 7 days repeated every 21 days. Individual dose reductions will be made on the basis of the AEs observed. Therapy will continue until disease progression, unacceptable toxicity as a result of MLN8237, or withdrawal of patient consent. Patients will be followed with history, physical, and blood tests at each visit to monitor for toxicity. Response and progression will be evaluated by CT/MRI scan and bone scan after every 3 cycles and determined using RECIST v1.1. PSA and serum chromogranin A and NSE will be followed every cycle. CTC counts by CellSearch will be performed at baseline, at 4-6 weeks, and upon progression. Patients will be followed for survival endpoints following completion of this study until death.
- Conditions
- Small Cell Prostate Cancer, Neuroendocrine Prostate Cancer, Prostate Adenocarcinoma Plus > 50% Immunohistochemical Staining for Neuroendocrine Markers
- Being tested
- MLN8237
- Keywords
- Metastatic prostate carcinoma
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN8237Drug
Also called Alisertib
MLN8237 will be administered orally. The study drug will be administered on an empty stomach with the patient remaining nothing by mouth (NPO), except for water and prescribed medications, for 2 hours before and 1 hour after each dose. Patients will be instructed to take each oral dose of MLN8237 with 8 ounces (1 cup, 240 mL) of water.
| Study group | Role | What they receive |
|---|---|---|
| All Patients | Experimental | MLN8237 at 50 mg twice daily for 7 days repeated every 21 days. Therapy will continue until disease progression, unacceptable toxicity as a result of MLN8237, or withdrawal of patient consent. Receives: Drug: MLN8237 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate, as Assessed by CT/MRI and Bone Scan, of Treatment With MLN8237 for Patients With Neuroendocrine Prostate Cancer
Evaluated per RECIST 1.1 guidelines: Complete response (CR) is defined as complete disappearance of all measurable and evaluable lesions by physical examination or imaging studies and normalization of PSA with no appearance of new lesions for > 1 month. Partial response (PR) is defined as a 30% 56 or greater reduction in the sum longest unidimensional diameter of all measurable lesions. There may be no new lesions. Stable Disease (SD) is characterized by patients who do not meet the criteria of PR and who are without signs of progressive disease for at least 1 month. Disease Progression (DP) is defined as a greater than 20% increase in the sum longest unidimensional diameters of the indicator lesions or the appearance of new lesions. Bone scan progression (evaluable disease only) is defined by PCWG2 criteria. Per consensus guidelines in CRPC, to be considered measurable, lymph nodes need to be at least 2 cm in greatest dimension and 1.5 cm in short axis.
Measured: one year
Secondary outcomes (4)
Progression-free Survival in Response to Therapy
Patients will be followed for survival endpoints following completion of this study until death.
Measured: 3 years
Overall Survival in Response to Therapy
Patients will be followed for survival endpoints following completion of this study until death
Measured: 3 years
Prostate-Specific Antigen (PSA) Test Response Rate
PSA to be followed every cycle to determine response.
Measured: 2 years
Circulating Tumor Cell (CTC) Response
CTC counts by CellSearch will be performed at baseline, at 4-6 weeks, and upon progression to determine response.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionJul 2016
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Small Cell Prostate CancerStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Himisha Beltran, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01799278
- Sponsor's protocol ID
- 1210013164
- Status last verified
- Dec 2017
- First submitted
- 22 Feb 2013
- Last updated
- 23 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Beltran H, Oromendia C, Danila DC, Montgomery B, Hoimes C, Szmulewitz RZ, Vaishampayan U, Armstrong AJ, Stein M, Pinski J, Mosquera JM, Sailer V, Bareja R, Romanel A, Gumpeni N, Sboner A, Dardenne E, Puca L, Prandi D, Rubin MA, Scher HI, Rickman DS, Demichelis F, Nanus DM, Ballman KV, Tagawa ST. A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers. Clin Cancer Res. 2019 Jan 1;25(1):43-51. doi: 10.1158/1078-0432.CCR-18-1912. Epub 2018 Sep 19.
PubMed 30232224
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of the Aurora Kinase A Inhibitor MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer
- ClinicalTrials.gov ID
- NCT01799278
- Acronym / sponsor ID
- 1210013164
- Conditions
- Small Cell Prostate Cancer, Neuroendocrine Prostate Cancer, Prostate Adenocarcinoma Plus > 50% Immunohistochemical Staining for Neuroendocrine Markers
- Keywords
- Metastatic prostate carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Feb 2013 (actual)
- Primary completion
- Jul 2016 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 26 Feb 2013 (estimated)
- Results
- Posted 29 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the response rate of MLN8237 in patients with histologically confirmed or clinically suspected metastatic neuroendocrine prostate cancer (NEPC). MLN8237 is an orally administered Aurora kinase A inhibitor that has demonstrated broad antitumor activity in vitro and in vivo. In preclinical models, aurora kinase inhibition resulted in dramatic and preferential anti-tumor activity in NEPC with suppression of neuroendocrine marker expression.
Detailed description
This is a multi-institutional single-arm, open-label Phase 2 trial evaluating MLN8237 in patients with histologically confirmed or clinically suspected metastatic neuroendocrine prostate cancer. Subjects will be treated with MLN8237 at 50 mg twice daily for 7 days repeated every 21 days. Individual dose reductions will be made on the basis of the AEs observed. Therapy will continue until disease progression, unacceptable toxicity as a result of MLN8237, or withdrawal of patient consent. Patients will be followed with history, physical, and blood tests at each visit to monitor for toxicity. Response and progression will be evaluated by CT/MRI scan and bone scan after every 3 cycles and determined using RECIST v1.1. PSA and serum chromogranin A and NSE will be followed every cycle. CTC counts by CellSearch will be performed at baseline, at 4-6 weeks, and upon progression. Patients will be followed for survival endpoints following completion of this study until death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Patients | Experimental | Drug: MLN8237MLN8237 at 50 mg twice daily for 7 days repeated every 21 days. Therapy will continue until disease progression, unacceptable toxicity as a result of MLN8237, or withdrawal of patient consent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Metastatic prostate carcinoma and at least one of the following:
- Serum chromogranin A level >5 x upper limit of normal and/or serum neuron specific enolase (NSE) >2x upper limit of normal
- Measurable disease by RECIST 1.1 with PCWG2 modifications
- Patients with pure small cell neuroendocrine carcinoma on histology are not required to have received prior androgen deprivation therapy (ADT) or castrate levels of testosterone, but their testosterone state should be maintained for the duration of the study. Other patients are required to have surgical or ongoing chemical castration, with baseline testosterone level <50ng/dL.
- Patients capable of fathering children must agree to use an effective method of contraception for the duration of the trial and should continue use for 4 months after last dose of study drug
Key exclusion criteria (12 listed)
- Radiation therapy to 25% of bone marrow within 2 weeks of first dose
- Residual > Grade 2 toxicity from prior treatment must have resolved with the exception of those explicitly described elsewhere in entry criteria
- Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
- Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed (see section 5.5)
- Severe or uncontrolled systemic infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MLN8237Also: AlisertibMLN8237 will be administered orally. The study drug will be administered on an empty stomach with the patient remaining nothing by mouth (NPO), except for water and prescribed medications, for 2 hours before and 1 hour after each dose. Patients will be instructed to take each oral dose of MLN8237 with 8 ounces (1 cup, 240 mL) of water. | Drug | All Patients |
Primary outcome
Response Rate, as Assessed by CT/MRI and Bone Scan, of Treatment With MLN8237 for Patients With Neuroendocrine Prostate Cancer
Time frame: one year
Evaluated per RECIST 1.1 guidelines: Complete response (CR) is defined as complete disappearance of all measurable and evaluable lesions by physical examination or imaging studies and normalization of PSA with no appearance of new lesions for > 1 month. Partial response (PR) is defined as a 30% 56 or greater reduction in the sum longest unidimensional diameter of all measurable lesions. There may be no new lesions. Stable Disease (SD) is characterized by patients who do not meet the criteria of PR and who are without signs of progressive disease for at least 1 month. Disease Progression (DP) is defined as a greater than 20% increase in the sum longest unidimensional diameters of the indicator lesions or the appearance of new lesions. Bone scan progression (evaluable disease only) is defined by PCWG2 criteria. Per consensus guidelines in CRPC, to be considered measurable, lymph nodes need to be at least 2 cm in greatest dimension and 1.5 cm in short axis.
4 secondary outcomes
Progression-free Survival in Response to Therapy
Time frame: 3 years
Overall Survival in Response to Therapy
Time frame: 3 years
Prostate-Specific Antigen (PSA) Test Response Rate
Time frame: 2 years
Circulating Tumor Cell (CTC) Response
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30232224Beltran H, Oromendia C, Danila DC, Montgomery B, Hoimes C, Szmulewitz RZ, Vaishampayan U, Armstrong AJ, Stein M, Pinski J, Mosquera JM, Sailer V, Bareja R, Romanel A, Gumpeni N, Sboner A, Dardenne E, Puca L, Prandi D, Rubin MA, Scher HI, Rickman DS, Demichelis F, Nanus DM, Ballman KV, Tagawa ST. A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers. Clin Cancer Res. 2019 Jan 1;25(1):43-51. doi: 10.1158/1078-0432.CCR-18-1912. Epub 2018 Sep 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Himisha Beltran, MD principal investigator
Weill Medical College of Cornell University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MLN8237 in people with Small Cell Prostate Cancer and Neuroendocrine Prostate Cancer, run by Weill Medical College of Cornell University at 8 sites 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 15 inclusion and 12 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 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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 phase mean?
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 29 Nov 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?
Response Rate, as Assessed by CT/MRI and Bone Scan, of Treatment With MLN8237 for Patients With Neuroendocrine Prostate Cancer (time frame: one year). 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 NCT01799278, which also lists 1 linked publication.
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 23 Jan 2018.