A Phase 1b Study of Enzalutamide Plus CC-115 in Men With Castration-Resistant Prostate Cancer (CRPC)
Overview
- Phase
- Phase 1
- Intervention
- Enzalutamide
- Conditions
- Prostate Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 40
- Locations
- 5
- Primary Endpoint
- establish the maximum tolerated dose (MTD)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The main purpose of this study to define the good and/or bad effects of the combination of enzalutamide and CC-115 in patients with castration-resistant prostate cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
- •NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
- •Males 18 years of age and above with a life expectancy of at least 6 months.
- •Histological or cytological proof of prostate cancer
- •Willing to provide a tumor sample via biopsy from a metastatic site of disease to be collected at screening if safe and feasible per treating investigator discretion. Adequate archival tissue can be used if available in lieu of baseline biopsy.
- •Documented progressive metastatic CRPC based on at least one of the following criteria:
- •Rise in PSA: a minimum of 3 rising levels, with an interval of at least 1 week between each determination. The last determination must have a value ≥1 ng/mL, obtained within 4 weeks of starting study drug
- •Measurable disease: new or progressive soft tissue disease on computerized tomography (CT) or magnetic resonance imaging
- •Radionuclide bone scan: at least 2 new bone lesions, as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria33
- •Serum testosterone \< 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue (agonist or antagonist) if they have not undergone orchiectomy
Exclusion Criteria
- •Prior exposure to enzalutamide, ARN-509, or other investigational AR-directed therapy
- •Prior exposure to abiraterone acetate, ketoconazole or other specific CYP-17 inhibitors
- •Prior exposure to agents specifically targeting both mTOR complexes (dual TORC1+TORC2 inhibitors) and/or PI3K/AKT pathways
- •Prior chemotherapy for castration resistant disease. Chemotherapy given in the castration-sensitive setting is permissible. At least 6 months from registration must have elapsed since chemotherapy was last received.
- •Symptomatic central nervous system metastases
- •Known history of acute or chronic pancreatitis
- •Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management
- •Clinically significant cardiac diseases, including any of the following:
- •Unstable angina pectoris
- •Myocardial infarction ≤ 3 months prior to registration
Arms & Interventions
Enzalutamide plus CC-115
The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until the maximum tolerated dose is identified. Participants at each site will participate in the dose escalation phase of the study. During the dose escalation phase, study participants will be assigned sequentially to three dose levels in groups (cohorts) of 3 to 6 subjects per dose level: Cohort 1: CC-115 at 5 mg dose twice a day \& enzalutamide at 160 mg once a day. Cohort 2: CC-115 at 10 mg dose twice a day \& enzalutamide at 160 mg once a day. The protocol has been amended to accrue an additional in the expansion phase treated at 7.5 mg BID. Amended to treat expansion group with 5mg BID of CC-115.
Intervention: Enzalutamide
Enzalutamide plus CC-115
The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until the maximum tolerated dose is identified. Participants at each site will participate in the dose escalation phase of the study. During the dose escalation phase, study participants will be assigned sequentially to three dose levels in groups (cohorts) of 3 to 6 subjects per dose level: Cohort 1: CC-115 at 5 mg dose twice a day \& enzalutamide at 160 mg once a day. Cohort 2: CC-115 at 10 mg dose twice a day \& enzalutamide at 160 mg once a day. The protocol has been amended to accrue an additional in the expansion phase treated at 7.5 mg BID. Amended to treat expansion group with 5mg BID of CC-115.
Intervention: CC-115
Outcomes
Primary Outcomes
establish the maximum tolerated dose (MTD)
Time Frame: 1 year
Subjects will be treated in cohorts of size three and six and the dosage will be escalated if the clinical toxicity is acceptable. The maximum tolerated dose is defined as the highest dose level with an observed incidence of DLT in no more than one out of six subjects treated at a particular dose level. A DLT will be determined by cycle 1 toxicity, although all-cycle toxicity will be recorded.