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

NCT02125084 | Completed Phase 1

• 1 other identifier: SCRI GU 99
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 5

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.

Conditions

Prostate Cancer

Keywords

Metastatic Prostate Cancer; Castrate-resistant; Enzalutamide; Everolimus

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD) of everolimus plus enzalutamide.

  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.

  6-8 months

• Prostate-specific antigen (PSA) response rate

  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.

  every 8 weeks for up to 24 months

• Number of patients with serious and non-serious adverse events.

  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.

  every 4 weeks up to 24 months

• Pharmacokinetic sampling for everolimus

  Levels of everolimus in blood samples will be collected from patients at selected timepoints prior to dosing during the first 3 cycles of treatment.

  Cycle 1, Day 1: prior to initial dose and 2hrs post-dose; Cycles 2 and 3, Day 1: prior to initial dose

Secondary Outcomes (3)

• Time to PSA progression

  every 8 weeks up to 24 months

• Overall Response Rate (ORR)

  every 8 weeks up to 24 months

• Progression-free survival (PFS)

  every 8 weeks up to 24 months

Study Arms (1)

Everolimus and Enzalutamide

EXPERIMENTAL

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; Drug: Enzalutamide

Interventions

Everolimus DRUG

Also known as: RAD001, Afinitor, Votubia

Everolimus and Enzalutamide

Enzalutamide DRUG

Also known as: MDV3100

Everolimus and Enzalutamide

Eligibility Criteria

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

You may qualify if:

• KEY POINTS:
• Adenocarcinoma of the prostate confirmed histologically.
• Metastatic disease confirmed by biopsy or imaging studies.
• 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.
• Chemotherapy-naive or previously treated with docetaxel for metastatic prostate cancer.
• ECOG of 0 to 2.
• 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.
• Adequate hematologic, hepatic and renal function.
• Adequate coagulation parameters and serum chemistries.
• Ability to swallow and retain oral medication.
• Life expectancy of 6 months or greater.
• Ability to understand the nature of the study and give written informed consent.

You may not qualify if:

• Treatment with more than 2 prior chemotherapy regimens.
• Previous treatment with enzalutamide or other investigational androgen receptor inhibitors.
• Previous treatment with PI3K/mTOR inhibitors.
• Known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or its excipients.
• 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.
• 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.
• CNS metastases.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (5)

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Center

St. Petersburg, Florida, 33705, United States

Location

Oncology Hematology Care Inc.

Cincinnati, Ohio, 45242, United States

Location

Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Everolimus; enzalutamide

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

• John D. Hainsworth, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

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 17, 2014
• First Posted: April 29, 2014
• Study Start: October 1, 2014
• Primary Completion: May 3, 2021
• Study Completion: May 3, 2021
• Last Updated: May 4, 2021

Record last verified: 2021-05

Locations

US (5)