A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer

• ClinicalTrials.gov Identifier: NCT02407054
• Recruitment Status: Active, not recruiting
• First Posted: April 2, 2015
• Last Update Posted: December 3, 2019
• Sponsor: Eli Lilly and Company
• Collaborator: Sarah Cannon Development Innovations
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY3023414 in combination with enzalutamide in men with prostate cancer.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer Metastatic	Drug: LY3023414; Drug: Enzalutamide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blinded, Placebo-Controlled, Randomized Phase II Study of Enzalutamide With or Without the PI3 Kinase/mTOR Inhibitor LY3023414 in Men With Metastatic Castration Resistant Prostate Cancer
• Actual Study Start Date: April 29, 2015
• Actual Primary Completion Date: September 26, 2018
• Estimated Study Completion Date: February 14, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: LY3023414 + Enzalutamide; Lead In- LY3023414 orally twice daily in first week for pharmacokinetics (PK); thereafter LY3023414 orally twice daily in combination with enzalutamide orally once daily for 28-day cycles. Randomization- LY3023414 orally twice daily in combination with enzalutamide orally once daily for 28-day cycles. Participants may remain on treatment until discontinuation criteria are met.	Drug: LY3023414; Administered orally; Drug: Enzalutamide; Administered orally
Active Comparator: Enzalutamide + Placebo; Enzalutamide orally once daily in combination with matching LY3023414 placebo orally twice daily for 28-day cycles. Participants may remain on treatment until discontinuation criteria are met.	Drug: Enzalutamide; Administered orally; Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death from Any Cause (Approximately 6 Months) ]

Secondary Outcome Measures :

1. Time to Disease Progression [ Time Frame: Baseline to Objective Disease Progression (Approximately 6 Months) ]
2. Percent Change from Baseline to 12 Weeks in Prostate Specific Antigen (PSA) [ Time Frame: Baseline, 12 Weeks ]
3. PK: Area Under the Concentration Curve (AUC) of LY3023414 and Enzalutamide [ Time Frame: Predose Cycle 1 to Cycle 3 Day 1 (Approximately 2 Months) ]
4. Proportion of Participants with a Complete or Partial Response (Overall Response Rate) [ Time Frame: Baseline to Second Measured Complete Response or Partial Response (Approximately 4 Months) ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate.
• Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• Prostate cancer progression documented by PSA and/or radiographic progression according to prostate cancer working group 2 (PCWG2).
• Prior abiraterone treatment completed at least 4 weeks prior to cycle 1 day 1. Participants must have failed prior abiraterone treatment.
• Surgically or medically castrated, with testosterone levels of < 50 nanograms/deciliter.
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
• Ability to swallow the study drugs whole.
• Adequate hematologic function.
• Adequate coagulation parameters, defined as international normalization ratio (INR) ≤ 2.
• Availability of tumor tissue from any time since diagnosis of prostate cancer disease. If no tumor samples are available the participant might still be eligible following discussion between the investigator and the medical monitor.

Exclusion Criteria:

• Prior cytotoxic chemotherapy, immunotherapy, a PI3K/AKT/mTOR agent (including TORC1 and TORC2 inhibitors), or RA 223 dichloride for the treatment of castration resistant prostate cancer (CRPC). Participants may have received docetaxel in the hormone-sensitive setting.
• Prior investigational new generation potent anti-androgen therapy (such as ARN 509).
• Prior treatment with enzalutamide.
• Pathological finding consistent with small cell carcinoma of the prostate.
• Prior systemic treatment with an azole drug (fluconazole, itraconazole) within 4 weeks of cycle 1 day 1.
• Known brain metastasis.
• History of (a) seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma); (b) loss of consciousness or transient ischemic attack within 12 months prior to day 1 of cycle 1.
• Uncontrolled hypertension (systolic blood pressure [BP] ≥ 160 millimeters of mercury [mmHg] or diastolic BP ≥ 95 mmHg).
• Have serious pre-existing medical conditions (at the discretion of the investigator).
• Have known acute or chronic leukemia or current hematologic malignancies that, in the judgment of the investigator and sponsor, may affect the interpretation of results.
• Have insulin-dependent diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c <7%.
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, grade ≥2 diarrhea, and malabsorption syndrome).
• Have a history of New York Heart Association (NYHA) Class ≥3, QTc interval > 480 milliseconds (ms) on screening electrocardiogram (ECG) per Friderica's formula, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration.
• Clinically significant electrolyte imbalance ≥ grade 2.
• Currently receiving treatment with therapeutic doses of warfarin sodium.
• Have initiated treatment with bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents (e.g. denosumab) ≤28 days prior to day 1 of cycle 1.
• Concurrent serious infections requiring parenteral antibiotic therapy.
• Have a second primary malignancy that in the judgment of the investigator and medical monitor may affect the interpretation of results.
• Have an active, known fungal, bacterial, and/or known viral infection.

Contacts and Locations

  Show 36 Study Locations

Sponsors and Collaborators

Eli Lilly and Company

Sarah Cannon Development Innovations

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Additional Information:

Click here for more information about this study: A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02407054 History of Changes
• Other Study ID Numbers: 15798; I6A-MC-CBBD ( Other Identifier: Eli Lilly and Company )
• First Posted: April 2, 2015
• Last Update Posted: December 3, 2019
• Last Verified: December 1, 2019

Additional relevant MeSH terms:

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