Back to resultsEnzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Everolimus
Enzalutamide
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Metastatic Prostate Cancer, Castrate-resistant, Enzalutamide, Everolimus
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
- 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.
Sites / Locations
- Florida Cancer Specialists
- Florida Cancer Center
- Oncology Hematology Care Inc.
- Tennessee Oncology
- Tennessee Oncology PLLC
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Everolimus and Enzalutamide
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
Time to PSA progression
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.
Overall Response Rate (ORR)
Soft tissue response rate [percentage of complete responders (CR) and partial responders (PR) per RECIST v1.1]
Progression-free survival (PFS)
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.
Full Information
NCT ID
NCT02125084
First Posted
April 17, 2014
Last Updated
May 3, 2021
Sponsor
SCRI Development Innovations, LLC
Collaborators
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02125084
Brief Title
Enzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
October 2014 (Actual)
Primary Completion Date
May 3, 2021 (Actual)
Study Completion Date
May 3, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SCRI Development Innovations, LLC
Collaborators
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Metastatic Prostate Cancer, Castrate-resistant, Enzalutamide, Everolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Everolimus and Enzalutamide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001, Afinitor, Votubia
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
MDV3100
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of everolimus plus enzalutamide.
Description
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.
Time Frame
6-8 months
Title
Prostate-specific antigen (PSA) response rate
Description
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.
Time Frame
every 8 weeks for up to 24 months
Title
Number of patients with serious and non-serious adverse events.
Description
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.
Time Frame
every 4 weeks up to 24 months
Title
Pharmacokinetic sampling for everolimus
Description
Levels of everolimus in blood samples will be collected from patients at selected timepoints prior to dosing during the first 3 cycles of treatment.
Time Frame
Cycle 1, Day 1: prior to initial dose and 2hrs post-dose; Cycles 2 and 3, Day 1: prior to initial dose
Secondary Outcome Measure Information:
Title
Time to PSA progression
Description
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.
Time Frame
every 8 weeks up to 24 months
Title
Overall Response Rate (ORR)
Description
Soft tissue response rate [percentage of complete responders (CR) and partial responders (PR) per RECIST v1.1]
Time Frame
every 8 weeks up to 24 months
Title
Progression-free survival (PFS)
Description
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.
Time Frame
every 8 weeks up to 24 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John D. Hainsworth, MD
Organizational Affiliation
SCRI Development Innovations, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
Florida Cancer Specialists
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33916
Country
United States
Facility Name
Florida Cancer Center
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
Facility Name
Oncology Hematology Care Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Tennessee Oncology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Tennessee Oncology PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Enzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer
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