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

NCT02106507 | Completed Phase 1

• 1 other identifier: 13-025
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Prostate Cancer

Keywords

Apalutamide; RAD001; Everolimus; Castration-resistant; 13-025; ARN-509

Outcome Measures

Primary Outcomes (3)

• 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.

  2 years

• 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.

  2 years

• 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.

  2 years

Secondary Outcomes (1)

• anti-tumor activity

  2 years

Study Arms (1)

Progressive Metastatic Castration-Resistant Prostate Cancer

EXPERIMENTAL

This 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.

Drug: apalutamide; Drug: Everolimus

Interventions

apalutamide DRUG

apalutamide, 240 mg/day, oral

Progressive Metastatic Castration-Resistant Prostate Cancer

Everolimus DRUG

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

Progressive Metastatic Castration-Resistant Prostate Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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);

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Aragon Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Everolimus

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Dana Rathkopf, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2014
• First Posted: April 8, 2014
• Study Start: April 1, 2014
• Primary Completion: June 28, 2021
• Study Completion: June 28, 2021
• Last Updated: May 26, 2023

Record last verified: 2023-05

Locations

US (1)