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Advanced Solid TumorsPhase 1NCT01094288

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

A Phase 1 study testing Alisertib and Docetaxel in people with Advanced Solid Tumors and Adenocarcinoma of the Prostate, run by Millennium Pharmaceuticals, Inc. at 4 sites in United States.

Completed

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

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alisertib and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
4 sitesUnited States
Study dates
17 Aug 2010to 4 Jan 2017
Phase
Phase 1
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 31Show fewer
  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Study site

    Indianapolis, Indiana

  • Study site

    Portland, Oregon

  • Study site

    San Antonio, Texas

  • Study site

    Seattle, Washington

Other trials in United States

About this study

Official title: A Phase 1 Study of MLN8237, an Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen

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.

Read the detailed description

The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have advanced solid tumors including castration-resistant prostate cancer.

The study enrolled approximately 41 patients. Participants were enrolled to receive:

  • Alisertib 10-40 mg + docetaxel 60-75 mg/m^2

All participants will receive alisertib (ECT) in dose escalating cohorts, orally, twice daily for 7 days followed by 14-day rest period in Cycle 1, 3 and onwards (21-day cycle) and orally twice daily from Day 3 to Day 7 followed by 14 day rest period in Cycle 2 [dose held for pharmacokinetic (PK) collection] along with docetaxel 75 mg/m^2, intravenous (IV) infusion on Day 1 of each cycle for maximum of 12 months, or until the occurrence of progressive disease (PD), unmanageable AEs or withdrawal of consent.

This multi-center trial is conducted in United States. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. Participants made multiple visits to the clinic, and were contacted every 12 weeks for up to 25.8 months after last dose of study drug for a follow-up assessment.

Being tested
Alisertib, Docetaxel

What participants receive

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

  • AlisertibDrug

    Also called MLN8237

    Alisertib ECT

  • DocetaxelDrug

    Docetaxel IV infusion

Study groups in NCT01094288
Study groupRoleWhat they receive
Alisertib + DocetaxelExperimentalAlisertib in escalating dose (10-40 mg), enteric-coated tablets (ECT), orally, twice daily for 7 days followed by 14-day rest period in Cycle 1, 3 and onwards (21-day cycle) and orally twice daily from Day 3 to Day 7 followed by 14 day rest period in Cycle 2 along with docetaxel 60-75 mg/m^2, intravenous (IV) infusion on Day 1 of each cycle for maximum of 12 months, or until the occurrence of progressive disease (PD), unmanageable adverse events (AEs) or withdrawal of consent. The starting alisertib dose is 10 mg, orally, twice daily (total 20 mg/day).
Receives: Drug: Alisertib; Drug: Docetaxel

What is being measured

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

  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

    Measured: From enrollment through 30 days after the last dose of study drug (approximately up to 77 months)

Secondary outcomes (13)

  1. Cmax: Maximum Observed Plasma Concentration for Docetaxel

    Measured: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

  2. AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel

    Measured: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

  3. AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel

    Measured: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

  4. Terminal Phase Elimination Half-life (T1/2) for Docetaxel

    Measured: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

  5. Cmax: Maximum Observed Plasma Concentration for Alisertib

    Measured: Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1

  6. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib

    Measured: Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1

  7. AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Day 7 Over the Dosing Interval for Alisertib

    Measured: Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1

  8. Overall Response Rate (ORR) Assessed for Overall Participant Population

    ORR is defined as percentage of participants who achieved complete response (CR) or partial response (PR) as assessed by response evaluation criteria in solid tumors (RECIST) v 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of longest diameter (LD) of target lesions in reference to Baseline. RECIST-Evaluable Population is subset of safety population who had measurable disease by RECIST v 1.1 at baseline and had at least 1 post baseline response. prostate specific antigen (PSA)-Evaluable Population is subset of the safety population who had a baseline PSA reference value (>5 ng/mL) and at least 12 weeks post-baseline PSA assessment for participants with no decline from baseline, or PSA progression within 12 weeks of treatment for participants with PSA decline from baseline.

    Measured: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

  9. Overall Response Rate for Prostate Cancer Participants

    ORR is defined as percentage of participants who achieved CR or PR as assessed by either RECIST v 1.1 or PSA response by prostate cancer working group 2 (PCWG2) criteria. According to RECIST v 1.1, CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. PSA response by PCWG2 is defined as PSA at least 50% decrease in PSA value from baseline for 2 consecutive evaluations. PCWG2 defines PSA progression as the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later.

    Measured: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

  10. Best Overall Response Rate Assessed by RECIST Criteria

    Best response rate is defined as the percentage of participants with CR, PR, CR+PR, stable disease (SD) and progressive disease (PD) as assessed by RECIST criteria 1.1 for target lesions and assessed by CT, PET or MRI. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

    Measured: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

  11. Best Overall Response Rate Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria

    Best Response Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria PSA response is defined as at least 50% decrease in PSA value from baseline for 2 consecutive evaluations.

    Measured: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

  12. Duration of Response

    Duration of response is defined as the time from the date of first documentation of a response to the date of first documented progressive disease (PD), or censored at last SD or better.

    Measured: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

  13. Duration of Stable Disease (SD)

    Duration of SD is defined as the time from first dose to first PD, or censored at last SD or better.

    Measured: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

Timeline

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

  1. First posted26 Mar 2010 (estimated)
  2. Study start17 Aug 2010
  3. Primary completion28 Feb 2014
  4. Study completion4 Jan 2017

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01094288
Sponsor's protocol ID
C14009
Status last verified
Oct 2018
First submitted
17 Mar 2010
Last updated
15 Feb 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alisertib and Docetaxel in people with Advanced Solid Tumors and Adenocarcinoma of the Prostate, run by Millennium Pharmaceuticals, Inc. at 4 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 18 inclusion and 31 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 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 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.

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 15 Feb 2019). 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?

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From enrollment through 30 days after the last dose of study drug (approximately up to 77 months)). 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 NCT01094288.

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 15 Feb 2019.

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