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Prostate CancerPhase 1NCT02106507

ARN 509 Plus Everolimus in Men With Progressive Metastatic Castration-Resistant Prostate Cancer After Treatment With Abiraterone Acetate

A Phase 1 study testing apalutamide and Everolimus in people with 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
Search all trials

Trial summary

The purpose of this study is to test the safety of the combination of apalutamide plus everolimus at different dose levels. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
apalutamide and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Apr 2014to 28 Jun 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with progressive metastatic disease based on any of the following:
  • Rise in PSA: minimum of 3 rising levels, with an interval of at least 1 week between each determination. The last determination must have a value ≥ 2 ng/mL, obtained within 4 weeks of starting study drug, or
  • Measurable disease: new or progressive soft tissue disease on CT or MRI scans, or
  • Radionuclide bone scan: at least 2 new bone lesions, as defined by the PCWG2 criteria1
  • Castration-resistant prostate cancer: patients must have surgical or ongoing chemical (androgen deprivation therapy) castration, with baseline testosterone level ≤ 50 ng/dL determined within 4 weeks of starting study drug.
  • Dose-Escalation: Prior treatment with abiraterone acetate. At least 4 weeks must have elapsed from the last dose of abiraterone acetate.
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  • Expansion Cohort only (if conducted in the study): Men with mCRPC and disease progression as defined by PCWG2 within 3 months (primary resistance); or after at least 6 months of treatment (acquired resistance) of starting treatment with abiraterone acetate. At least 4 weeks must have elapsed from the last dose of abiraterone .acetate
  • Physiologic doses of corticosteroids are allowed (i.e. no more than 10 mg prednisone daily).
  • Patients currently receiving bone loss prevention treatment (e.g. bisphosphonates, denosumab, etc.) must be on a stable dose for at least 4 weeks prior to starting study treatment.
  • Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) 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 (e.g., bicalutamide, flutamide, nilutamide); 5-α reductase inhibitors (e.g., dutasteride, finasteride, aminoglutethimide); estrogens; ketoconazole and other anti-cancer pharmacologic therapy prior to enrollment.
  • At least 6 weeks must have elapsed from the use of bicalutamide if used as part of an initial combined androgen blockage therapy for more than 6 months or if used as second line hormonal therapy and associated with a PSA response of at least 3 months duration.
  • At least 12 weeks must have elapsed from the use of Strontium-89, Radium-223 or any investigational or approved immunotherapy (e.g., Provenge) prior to starting study drug.
  • At least 4 weeks must have elapsed from the use of any other investigational agent prior to starting study drug.
  • At least 4 weeks must have elapsed from major surgery prior to starting study drug.
  • Patients with treated, non-progressive epidural disease are eligible.
  • At least 18 years of age, with a life expectancy of at least 3 months.
  • ECOG performance status 0 or 1 (2 is allowed only if due to bone pain).
  • Toxicities related to prior therapy must either have returned to ≤ Grade 1, baseline, or deemed irreversible.
  • 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 cells/mm3, 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
  • Adequate blood clotting time with an INR <2
  • Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Who cannot join

  • Prior treatment with apalutamide, or PI3K/mTOR pathway inhibitors.
  • History of, or current metastases in the brain, meninges, or untreated spinal cord compression.
  • Patients previously treated with chemotherapy for mCRPC. At least 12 months must have elapsed from chemotherapy given in the adjuvant or neoadjuvant setting.
  • History of any other malignancy within the previous 5 years except for the following: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, stage I or II cancer currently in complete remission, or any other cancer that has been in complete remission for at least 5 years.
  • History of seizure or condition that may predispose to seizure (e.g., prior stroke within 1 year of starting study drug, brain arteriovenous malformation)
  • Concurrent therapy with medications known to have seizure potential
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  • Known intolerance or hypersensitivity to Vitamin E, everolimus or to rapamycin derivatives.
  • Use of herbal products that may decrease PSA levels (e.g., saw palmetto).
  • Known human immunodeficiency virus (HIV) infection.
  • Patients who have received live attenuated vaccines within 1 week of start of Everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study.
  • Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing.
  • Male patients whose sexual partner(s) are women of child-bearing potential (WOCBP) who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment. Highly effective contraception methods include combination of any two of the following (a+b or a+c or b+c):
  • Use of oral, injected or implanted hormonal methods of contraception or;
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS);
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
  • Total abstinence or;
  • Male/female sterilization.
  • Patients with a known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus.
  • Patients with uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
  • Patients who have any severe and/or uncontrolled medical conditions such as:
  • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease ii. Symptomatic congestive heart failure of New York heart Association Class III or IV iii. active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA), iv. known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), v. active, bleeding diathesis;

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: Phase 1b Study of ARN 509 Plus Everolimus in Men With Progressive Metastatic Castration-Resistant Prostate Cancer After Treatment With Abiraterone Acetate

The purpose of this study is to test the safety of the combination of apalutamide plus everolimus at different dose levels.

Conditions
Prostate Cancer
Being tested
apalutamide, Everolimus
Keywords
Apalutamide, RAD001, Everolimus, Castration-resistant, 13-025, ARN-509
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • apalutamideDrug

    apalutamide, 240 mg/day, oral

  • EverolimusDrug

    5 mg/day of everolimus dose of everolimus will be escalated to 10 mg/day depending on the safety seen during dose escalation and steady-state trough drug levels as recommended

Study groups in NCT02106507
Study groupRoleWhat they receive
Progressive Metastatic Castration-Resistant Prostate CancerExperimentalThis is a single-institution Phase 1b dose-escalation study in which eligible patients with progressive mCRPC will receive oral doses of apalutamide in combination with everolimus.
Receives: Drug: apalutamide; Drug: Everolimus

What is being measured

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

  1. safety

    Safety will be evaluated according to the NCI Common Terminology Criteria for Adverse Events V4.0 (CTCAE). Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests throughout the conduct of the study.

    Measured: 2 years

  2. pharmacokinetics

    Pharmacokinetic parameters (Cmax, Tmax, AUC(INF), AUC(TAU), will be derived from blood to obtain everolimus concentration or plasma to obtain apalutamide and it's major metabolite concentration versus time data for patients in the dose escalation cohorts.

    Measured: 2 years

  3. maximum tolerated dose (MTD)

    The first phase of the study will examine the safety of apalutamide in combination with everolimus in patients with metastatic castration-resistant prostate cancer. Up to 2 dose levels will be tested. A standard "3 plus 3" dose escalation rule will be used in order to determine the MTD/RP2D. Patients will be treated in cohorts of three and the dosage will be escalated if the clinical toxicity is acceptable. The MTD is defined as the highest dose with an observed incidence of dose limiting toxicity (DLT) in no more than one out of six patients treated at a particular dose level.

    Measured: 2 years

Secondary outcomes (1)

  1. anti-tumor activity

    Tumor biopsies pre- and post-treatment will be collected to evaluate for downstream indicators of PI3K pathway modulation, including pS6K, p4EBP1, pAKT, AR, PHLLP 1 and 2, and additional pathways of interest if safe and feasible per treating investigator. In lieu of biopsy, if a patient is having an elective or clinical resection/surgery and tissue is already being removed, some of that tissue may be collected for research purposes to fulfill the biopsy requirement for that timepoint. These biomarkers will be measured at baseline and cycle 2 and after treatment to explore the association between changes in the tumor biomarkers and progression-free survival.

    Measured: 2 years

Timeline

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

  1. First posted8 Apr 2014 (estimated)
  2. Study startApr 2014
  3. Primary completion28 Jun 2021
  4. Study completion28 Jun 2021

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02106507
Sponsor's protocol ID
13-025
Status last verified
May 2023
First submitted
3 Apr 2014
Last updated
26 May 2023
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing apalutamide and Everolimus in people with 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 27 inclusion and 22 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 26 May 2023. 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

safety (time frame: 2 years). The study lists 3 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 NCT02106507.

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 26 May 2023; AzTrials last refreshed its copy on 6 Nov 2026.

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