Clinical Trials /

Use of an Experimental Drug, CC-115, With Enzalutamide in Men With Castration-Resistant Prostate Cancer

NCT02833883

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Use of an Experimental Drug, CC-115, With Enzalutamide in Men With Castration-Resistant Prostate Cancer
  • Official Title: A Phase 1b Study of Enzalutamide Plus CC-115 in Men With Castration-Resistant Prostate Cancer (CRPC)

Clinical Trial IDs

  • ORG STUDY ID: 16-074
  • SECONDARY ID: c15-160
  • NCT ID: NCT02833883

Conditions

  • Prostate Cancer
  • Castration Resistant Prostate Cancer

Interventions

DrugSynonymsArms
EnzalutamideEnzalutamide plus CC-115
CC-115Enzalutamide plus CC-115

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Enzalutamide plus CC-115ExperimentalThe 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.
  • Enzalutamide
  • CC-115

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 metastatic tissue can be used if available in lieu of baseline
             biopsy if done when patient had CRPC.

          -  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

          -  ECOG performance status of 0-1

          -  Finasteride, bicalutamide and nilutamide discontinued at least 4 weeks prior to
             registration.

          -  Physiologic doses of corticosteroids are permitted (i.e., no more than 10mg of
             prednisone daily).

          -  At least 4 weeks must have elapsed from the use of palliative radiation, Strontium-89,
             Radium-223, or approved immunotherapy prior to registration.

          -  Less than or equal to 5 half lives or 4 weeks, whichever is shorter, from the use of
             any investigational therapy prior to registration.

          -  Normal organ function with acceptable initial laboratory values within 14 days of
             registration.

               -  ANC ≥ 1,500/μl

               -  Hemoglobin ≥ 9g/dL

               -  Platelet count ≥ 100,000/μl

               -  Creatinine ≤ 1.5 x the institutional upper limit of normal (ULN), or 24-hr
                  clearance ≥50 mL/min

               -  Potassium ≥ 3.5 mmol/L (within institutional normal range, or correctable with
                  supplements)

               -  Bilirubin ≤ 1.5 x ULN (unless documented Gilbert's disease)

               -  SGOT (AST) ≤ 2.5 x ULN

               -  SGPT (ALT) ≤ 2.5 x ULN

               -  Glycated hemoglobin (HbA1c < 6.4%

          -  Able to take oral medication without crushing, dissolving or chewing tablets.

          -  Able to adhere to the study visit schedule and other protocol requirements.

        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

               -  Other clinically significant heart disease such as congestive heart failure
                  requiring treatment or uncontrolled hypertension

          -  Uncontrolled diabetes mellitus

          -  Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
             active or uncontrolled infection) that could cause unacceptable safety risks or
             compromise compliance with the protocol

          -  Major surgery ≤ 2 weeks prior to registration or who have not recovered from side
             effects of such therapy. Subjects must have recovered from any effects of recent
             radiotherapy that might confound the safety evaluation of study drug.

          -  Hematopoietic stem cell transplant ≤ 3 months prior to registration.

          -  Adults of reproductive potential not employing two forms of birth control:

               -  Males having partners who are female with child-bearing potential must agree that
                  they and/or their partners will use at least two effective contraceptive methods
                  (including one barrier method) when engaging in reproductive sexual activity
                  throughout the study from the time of informed consent, and will avoid conceiving
                  for 28 days after the last dose of CC-115.

          -  Known human immunodeficiency virus (HIV) infection

          -  Known chronic hepatitis B or C virus (HBV/HCV) infection

          -  Concurrent active second malignancy for which the subject is receiving therapy, other
             than non-melanomatous skin cancer or superficial transitional cell carcinoma.

          -  History of seizure or any condition that may predispose to seizure including, but not
             limited to, underlying brain injury, stroke in the past 6 months, primary brain
             tumors, brain metastases

          -  Active treatment with medications that lower the seizure threshold which cannot be
             held:

               -  Aminophylline/theophylline;

               -  Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone);

               -  Bupropion;

               -  Lithium;

               -  Pethidine;

               -  Phenothiazine antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine);

               -  Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine,
                  doxepin, imipramine, maprotiline, mirtazapine).

          -  Any other condition which, in the opinion of the Investigator, would preclude
             participation in this trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:establish the maximum tolerated dose (MTD)
Time Frame:1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Enzalutamide
  • CC-115
  • 16-074

Last Updated

July 31, 2019