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Metastatic Castration-Resistant Prostate CancerPhase 2NCT02091531

Dual mTOR Inhibitor MLN0128 in Advanced Castration-Resistant Prostate Cancer (CRPC) Patients

A Phase 2 study testing MLN0128 in people with Metastatic Castration-Resistant Prostate Cancer, run by Memorial Sloan Kettering Cancer Center 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
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Trial summary

This is a phase II study which will test the study drug MLN0128 in patients with castration resistant prostate cancer who have received chemotherapy in the past. Phase II clinical trials test how well an investigational drug works in treating a specific cancer. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
MLN0128
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Mar 2014to Oct 2018
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

  • Histologically confirmed prostate cancer with progressive metastatic disease based on any of the following: i) a rise in PSA, ii) transaxial imaging, or iii) radionuclide bone scan.
  • PSA - a minimum of 3 consecutive rising levels, with an interval of ≥
  • 1 week between each determination. The last determination must have a minimal value of ≥ 2 ng/mL and be determined within two weeks prior to enrollment.
  • Measurable Disease - patients showing new or progressive soft tissue masses on CT or MRI scans as defined by the PCWG2 criteria21
  • Radionuclide bone scan - at least two new metastatic lesions.
  • Detectable metastases by bone scan, CT-scan or MRI.
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  • Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration).
  • For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial.
  • Castrate levels of serum testosterone < 50 ng/dL determined within 4 weeks prior to starting treatment.
  • Patients who are receiving an anti-androgen as part of their first-line hormonal therapy must have shown progression of disease off the anti-androgen prior to enrollment.
  • At least 4 weeks must have elapsed from the use of androgen receptor antagonists (i.e., flutamide, nilutamide, bicalutamide, enzalutamide ); 5-α reductase inhibitors (i.e., finasteride, aminoglutethimide); abiraterone acetate; estrogens; nitrosoureas, mitomycin C, isotype therapy, ketoconazole, chemotherapy and other anti-cancer pharmacologic therapy prior to beginning protocol therapy.
  • At least 8 weeks must have elapsed from the use of Strontium-89, Radium-223, Samarium-153, or immunotherapy (e.g., Provenge) prior to beginning protocol therapy.
  • At least 4 weeks must have elapsed from the use of any investigational agent prior to beginning protocol therapy.
  • Note: Prior treatment with PI3K/mTOR pathway inhibitors prohibited.
  • At least 4 weeks must have elapsed from major surgery.
  • Toxicities related to prior therapy must either have returned to ≤ Grade 1, baseline or deemed irreversible.
  • Patients with treated, non-progressive epidural disease are eligible.
  • KPS performance status 70-100% (50-60% is allowed only if due to bone pain)
  • At least 18 years of age, with a life expectancy at least 3 months.
  • Patient must be willing to comply with study procedures.
  • Physical and laboratory test findings
  • Adequate hepatic function with serum bilirubin ≤ 1.5 times the upper institutional limits of normal (ULN), ALT and AST ≤ 2.5 x ULN. Patients with a history of Gilbert's syndrome may be enrolled if the total bilirubin is < 3 mg/dL with a predominance of indirect bilirubin
  • Adequate renal function with serum creatinine ≤ 1.5 x ULN.
  • Adequate hematologic function with absolute neutrophil counts ≥ 1,500 cell/mm3 and platelets ≥ 100,000 cells/mm3 and hemoglobin value ≥ 9 g/dL (Note: patients whose anemia has been corrected to a hemoglobin value ≥ 9 g/dL with blood transfusions are allowed).
  • Electrolytes (including potassium, sodium, and serum calcium corrected for albumin or ionized calcium) must be within normal limits.
  • Left ventricular ejection fraction (LVEF) no more than 5 absolute percentage points below the institutional standard of normal as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks prior to first study drug administration (ie, if the institutional normal is 50%, subject's LVEF may be as low as 45% to be eligible for the study)

Who cannot join

  • Patients that meet any of the criteria listed below will not be eligible for study entry:
  • History of, or current known metastases in the brain or untreated spinal cord compression;
  • History of another malignancy within the previous 2 years except for the following:
  • Adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer,
  • Adequately treated Stage I or II cancer currently in complete remission, or any other cancer that has been in complete remission for at least 2 years;
  • Prior treatment with PI3K/mTOR pathway inhibitors;
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  • Diabetes mellitus on active treatment, or subjects with either of the following:
  • Fasting blood glucose (FBG) ≥ 126 mg/dL (7.0 mmol/L), or
  • HbA1c ≥ 6.5%;
  • Use of herbal products that may decrease PSA levels (i.e., saw palmetto) or systemic corticosteroid greater than the equivalent of 10 mg of prednisone per day during the 4 weeks prior to screening or plans to initiate treatment with the above during the entire duration of the study;
  • Any history of unstable angina, myocardial infarction, New York Heart Association (NYHA) Class III or IV heart failure, and/or pulmonary hypertension;
  • Significant active cardiovascular disease including:
  • Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mmHg) b. Grade 3 or higher valvular disease c. Grade 3 or higher atrial fibrillation d. Grade 3 or higher bradycardia e. Endocarditis f. Pulmonary embolism g. Recent cerebrovascular accident within 6 months prior to enrollment
  • A requirement for positive inotropic support (excluding digoxin) or serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) within 1 year prior to screening
  • A pacemaker or implantable cardiac defibrillator
  • Known history of infection with human immunodeficiency virus (HIV), based on medical history (screening labs to rule out HIV infection are not required);
  • Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 2 Study of the Dual mTOR Inhibitor MLN0128 in Patients With Metastatic Castration-Resistant Prostate Cancer (CRPC)

This is a phase II study which will test the study drug MLN0128 in patients with castration resistant prostate cancer who have received chemotherapy in the past. Phase II clinical trials test how well an investigational drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. MLN0128 is not approved by the FDA.

The purpose of this study is to see what effects (good and bad) the study drug MLN0128 has on the patient and the cancer. MLN0128 is a drug that belongs to a class of drugs called "mTOR kinase inhibitors". A protein, called "mTOR" inside the cells in the body, plays a role in controlling how cells grow. In some cancer cells, mTOR may be over-active. This over-activity may cause some cancer cells to grow out of control. Research has shown that mTOR inhibitors can block this overactivity and may help stop or slow down the growth of some types of cancer cells.

Being tested
MLN0128
Keywords
mTOR Inhibitor MLN0128, PSA, 13-143

What participants receive

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

  • MLN0128Drug

Study groups in NCT02091531
Study groupRoleWhat they receive
MLN0128ExperimentalPatients will be treated with the established phase II dose of MLN0128 (4mg po daily continuously; 1 cycle=4 weeks) to assess mechanisms of sensitivity and resistance in men with CRPC who have received either enzalutamide and/or abiraterone.
Receives: Drug: MLN0128

What is being measured

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

  1. Median Time on Treatment

    from the start of treatment, as defined by the Prostate Cancer Working Group 2 (PCWG2) guidelines.

    Measured: Up to 8 months

Secondary outcomes (2)

  1. Median PSA Rise at End of Treatment as Compared to Baseline

    Summary tables and waterfall plots describing change in PSA relative to baseline will be reported at end of treatment

    Measured: Duration of Treatment, up to 30 weeks

  2. Best Response

    We propose to study both FDG and optional FDHT PET imaging at baseline, 4 weeks after treatment initiation and at the time of progression (end-of-treatment), and to correlate the changes with treatment response. Response and progression will be evaluated in this study using a combination of the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee and modified for prostate cancer and the guidelines for prostate cancer endpoints developed by the Prostate Cancer Clinical Trials Working Group (PCWG2).21

    Measured: Duration of Treatment, up to 30 weeks

Timeline

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

  1. First posted19 Mar 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionOct 2018
  4. Study completionOct 2018

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 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
NCT02091531
Sponsor's protocol ID
13-143
Status last verified
Oct 2018
First submitted
14 Mar 2014
Last updated
21 Nov 2019

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MLN0128 in people with Metastatic Castration-Resistant Prostate Cancer, run by Memorial Sloan Kettering Cancer Center 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 26 inclusion and 17 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 21 Nov 2019. 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 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 Oct 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?

Median Time on Treatment (time frame: Up to 8 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 NCT02091531.

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 21 Nov 2019.

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