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

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ClinicalTrials.gov Identifier: NCT02833883
Recruitment Status : Recruiting
First Posted : July 14, 2016
Last Update Posted : October 3, 2018
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Castration Resistant Prostate Cancer Drug: Enzalutamide Drug: CC-115 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Enzalutamide Plus CC-115 in Men With Castration-Resistant Prostate Cancer (CRPC)
Actual Study Start Date : July 2016
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: 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 17-30 patients in the expansion phase treated at 7.5 mg BID.
Drug: Enzalutamide
Drug: CC-115



Primary Outcome Measures :
  1. 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.



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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02833883


Contacts
Contact: Dana Rathkopf, MD 646-422-4379
Contact: Wassim Abida, MD, PhD 646-422-4633

Locations
United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Felix Feng, MD    415-502-7222      
United States, Maryland
John Hopkins Medical Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Emmanuel Antonarakis, MBBCh    410-464-6641      
Principal Investigator: Emmanuel Antonarakis, MBBCh         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Dana Rathkopf, MD    646-422-4379      
Contact: Wassim Abida, MD, PhD    646-422-4633      
Principal Investigator: Dana Rathkopf, MD         
United States, Washington
University of Washington School of Medicine Recruiting
Seattle, Washington, United States, 98109
Contact: Heather Cheng, MD, PhD    206-606-7486      
Principal Investigator: Heather Cheng, MD, PhD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Celgene Corporation
Investigators
Principal Investigator: Dana Rathkopf, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02833883     History of Changes
Other Study ID Numbers: 16-074
c15-160 ( Other Identifier: Prostate Cancer Clinical Trials Consortium, LLC (PCCTC) )
First Posted: July 14, 2016    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:
Enzalutamide
CC-115
16-074

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases