Trial record 7 of 48 for:    mdv3100 | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by SCRI Development Innovations, LLC
Novartis Pharmaceuticals
Information provided by (Responsible Party):
SCRI Development Innovations, LLC Identifier:
First received: April 17, 2014
Last updated: September 8, 2014
Last verified: September 2014

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 Intervention Phase
Prostate Cancer, Castrate-resistant
Drug: Everolimus
Drug: Enzalutamide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Escalating doses of everolimus will be tested with standard dose enzalutamide. [ Time Frame: 6-8 months ] [ Designated as safety issue: Yes ]
    Establish the optimal daily dose of everolimus to be administered in conjunction with a standard daily dose of enzalutamide

  • Prostate-specific antigen (PSA) response rate decline of greater than 50 percent. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Obtain preliminary information regarding the efficacy of the combination in the treatment of men with docetaxel-refractory metastatic prostate cancer

  • Number of patients with serious and non-serious adverse events. [ Time Frame: every 4 weeks up to 24 months ] [ Designated as safety issue: Yes ]
    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.

  • Levels of everolimus in blood samples collected from patients at selected timepoints prior to everolimus dosing during the first 3 cycles of treatment. [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PSA response rate (decline of greater than 85 %) [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]
  • Time to PSA progression [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]
    Restaging will occur every 8 weeks from date of first treatment until date of first PSA progression.

  • Overall Response Rate (ORR) [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]
    Soft tissue response rate [percentage of complete responders (CR) and partial responders (PR) per RECIST v1.1]

  • Progression-free survival (PFS) [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]
    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.

Estimated Enrollment: 43
Study Start Date: August 2014
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older
Genders 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02125084

Contact: Sarah Cannon Research Institute 1-877-691-7274

United States, Ohio
Oncology Hematology Care Inc. Recruiting
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Tennessee Oncology PLLC Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Novartis Pharmaceuticals
Study Chair: John D. Hainsworth, MD SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT02125084     History of Changes
Other Study ID Numbers: SCRI GU 99
Study First Received: April 17, 2014
Last Updated: September 8, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents processed this record on September 22, 2014