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

NCT02833883 | Completed Phase 1

• 2 other identifiers: 16-074c15-160
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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.

Conditions

Prostate Cancer; Castration Resistant Prostate Cancer

Keywords

Enzalutamide; CC-115; 16-074

Outcome Measures

Primary Outcomes (1)

• establish the maximum tolerated dose (MTD)

  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.

  1 year

Study Arms (1)

Enzalutamide plus CC-115

EXPERIMENTAL

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.

Drug: Enzalutamide; Drug: CC-115

Interventions

Enzalutamide DRUG

Enzalutamide plus CC-115

CC-115 DRUG

Enzalutamide plus CC-115

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (5)

University of California San Francisco

San Francisco, California, 94143, United States

Location

John Hopkins Medical Center

Baltimore, Maryland, 21287, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27701, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Zhao JL, Antonarakis ES, Cheng HH, George DJ, Aggarwal R, Riedel E, Sumiyoshi T, Schonhoft JD, Anderson A, Mao N, Haywood S, Decker B, Curley T, Abida W, Feng FY, Knudsen K, Carver B, Lacouture ME, Wyatt AW, Rathkopf D. Phase 1b study of enzalutamide plus CC-115, a dual mTORC1/2 and DNA-PK inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC). Br J Cancer. 2024 Jan;130(1):53-62. doi: 10.1038/s41416-023-02487-5. Epub 2023 Nov 18.

  PMID: 37980367 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one

Condition Hierarchy (Ancestors)

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

Study Officials

• Dana Rathkopf, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 14, 2016
• Study Start: July 1, 2016
• Primary Completion: January 13, 2023
• Study Completion: January 13, 2023
• Last Updated: January 19, 2023

Record last verified: 2023-01

Locations

US (5)