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Enzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02125084
Recruitment Status : Active, not recruiting
First Posted : April 29, 2014
Last Update Posted : April 12, 2019
Novartis Pharmaceuticals
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
The purpose of this study is to determine the safety and efficacy of a novel combination of agents, enzalutamide and everolimus, for the treatment of patients with metastatic castrate-resistant prostate cancer who have never received prior chemotherapy, or who have previously received docetaxel chemotherapy and have progressive disease.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Everolimus Drug: Enzalutamide Phase 1

Detailed Description:
This is a multi-center, open-label, Phase I study with an expansion cohort, in patients with metastatic Castrate-Resistant Prostate Cancer (CRPC) who are chemotherapy-naive or have previously received docetaxel chemotherapy and have progressive disease at the time of study entry. The dose escalation phase of this study will establish the optimum daily dose of everolimus that can be delivered along with a standard daily dose of enzalutamide to patients with metastatic CRPC. Eligible patients must have evaluable (elevated PSA) or measurable disease (per RECIST v1.1). Following completion of the dose escalation phase, an additional cohort of patients will be treated at the maximum tolerated dose (MTD) to give preliminary information regarding the efficacy of this combination.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Enzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer: A Phase I Study With a Maximum Tolerated Dose Expansion Cohort
Study Start Date : October 2014
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Everolimus and Enzalutamide

Dose Escalation Phase (18 patients): 3-6 patients will be treated at each dose level until the Maximum Tolerated Dose (MTD) is determined.

  • Everolimus: Orally (PO) once daily (dose to be determined;
  • Enzalutamide: 160mg (four 40mg capsules) PO continuous daily dosing.

Dose Expansion Phase (23 patients): Everolimus and Enzalutamide to be administered using the MTD determined in the dose escalation phase.

Drug: Everolimus
Other Names:
  • RAD001
  • Afinitor
  • Votubia

Drug: Enzalutamide
Other Name: MDV3100

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of everolimus plus enzalutamide. [ Time Frame: 6-8 months ]
    MTD will be determined by testing increasing doses of everolimus with standard dose enzalutamide in 3-patient dose escalation cohorts. The MTD is defined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during 1 cycle (28 days) of therapy, assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

  2. Prostate-specific antigen (PSA) response rate [ Time Frame: every 8 weeks for up to 24 months ]
    PSA response will be measured by the percent decreased from the reported baseline value. The proportion of patients with documented PSA decreases of 50% and 85% in PSA levels will be reported separately.

  3. Number of patients with serious and non-serious adverse events. [ Time Frame: every 4 weeks up to 24 months ]
    Evaluate the safety of the combination per CTCAE v4.0, every 4 weeks from date of first study treatment until the date of documented progression, up to 24 months.

  4. Pharmacokinetic sampling for everolimus [ Time Frame: Cycle 1, Day 1: prior to initial dose and 2hrs post-dose; Cycles 2 and 3, Day 1: prior to initial dose ]
    Levels of everolimus in blood samples will be collected from patients at selected timepoints prior to dosing during the first 3 cycles of treatment.

Secondary Outcome Measures :
  1. Time to PSA progression [ Time Frame: every 8 weeks up to 24 months ]
    Defined as the time from date of first protocol treatment until date of PSA progression. PSA progression is defined as when patient has both a ≥25% increase above the nadir or baseline value and when the absolute increase is ≥2ng/mL.

  2. Overall Response Rate (ORR) [ Time Frame: every 8 weeks up to 24 months ]
    Soft tissue response rate [percentage of complete responders (CR) and partial responders (PR) per RECIST v1.1]

  3. Progression-free survival (PFS) [ Time Frame: every 8 weeks up to 24 months ]
    Restaging will occur every 8 weeks from date of first treatment until date of first progression, or date of death from any cause, whichever comes first - up to 24 months.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:


  1. Adenocarcinoma of the prostate confirmed histologically.
  2. Metastatic disease confirmed by biopsy or imaging studies.
  3. Castrate-resistant prostate cancer (i.e., progression of prostate cancer while receiving standard androgen ablation therapy, orchiectomy or luteinizing hormone-releasing hormone [LHRH] antagonist). Castrate levels of serum testosterone must be documented at progression in patients who have not had an orchiectomy.
  4. Chemotherapy-naive or previously treated with docetaxel for metastatic prostate cancer.
  5. ECOG of 0 to 2.
  6. Patients must have progressive metastatic prostate cancer by at least 1 of the following criteria:

    • Progression of measurable lesions defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
    • Bone progression defined by 2 or more new lesions on bone scan.
    • PSA progression is determined by a minimum of two rising PSA levels with an interval of 1 week or greater between each determination. The screening PSA measurement (documenting progression) must be greater than or equal to 2 ng/mL.
  7. Adequate hematologic, hepatic and renal function.
  8. Adequate coagulation parameters and serum chemistries.
  9. Ability to swallow and retain oral medication.
  10. Life expectancy of 6 months or greater.
  11. Ability to understand the nature of the study and give written informed consent.

Exclusion Criteria:

  1. Treatment with more than 2 prior chemotherapy regimens.
  2. Previous treatment with enzalutamide or other investigational androgen receptor inhibitors.
  3. Previous treatment with PI3K/mTOR inhibitors.
  4. Known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or its excipients.
  5. Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of study drug is required.
  6. Most recent chemotherapy ≤21 days from first dose of study treatment and/or patient did not recover from most recent chemotherapy side effects prior to study entry.
  7. CNS metastases.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02125084

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United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33916
Florida Cancer Center
Saint Petersburg, Florida, United States, 33705
United States, Ohio
Oncology Hematology Care Inc.
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Tennessee Oncology
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology PLLC
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Novartis Pharmaceuticals
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Study Chair: John D. Hainsworth, MD SCRI Development Innovations, LLC

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Responsible Party: SCRI Development Innovations, LLC Identifier: NCT02125084     History of Changes
Other Study ID Numbers: SCRI GU 99
First Posted: April 29, 2014    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019

Keywords provided by SCRI Development Innovations, LLC:
Metastatic Prostate Cancer

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents