A Phase 1, Open-label, Functional Imaging Study to Assess Whether CC-90011 Reverses the Castration Resistance Due to Lineage Switch in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC) Who Have Failed Enzalutamide as Last Prior Therapy, Followed by a Dose Finding Study of CC-90011 Combined With Abiraterone and Prednisone
Overview
- Phase
- Phase 1
- Intervention
- CC-90011
- Conditions
- Prostatic Neoplasms
- Sponsor
- Celgene
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Assessment of androgen receptor (AR) level
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open-label, positron emission tomography (PET) imaging Proof of Biology (POB) study to determine whether CC -90011 reverses, by the induction of androgen receptor (AR) expression, the castration resistance, due to lineage switch, in participants with mCRPC that have failed enzalutamide as last prior therapy. This study aims to assess whether CC-90011 can induce AR expression and, consequently, re-sensitize tumors to anti-hormonal therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant is a male ≥ 18 years of age the time of signing the informed consent form (ICF).
- •Histologically confirmed adenocarcinoma of the prostate.
- •Surgically or medically castrated, with testosterone levels of \< 50 ng/dL (\<2.0 nM). If the participant is being treated with luteinizing hormone-releasing hormone (LHRH) agonists/antagonists (participant who have not undergone orchiectomy) this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study.
- •Participants must have failed prior therapy with enzalutamide or apalutamide
- •Has completed at least 12 weeks of prior continuous therapy with enzalutamide or apalutamide .
- •Has been without enzalutamide, or apalutamide treatment for \>30 days prior to initiation of study treatment.
- •Documented prostate cancer progression as assessed by the investigator with one of the following:
- •Prostate-specific antigen (PSA) progression defined by a minimum of 3 rising PSA levels with an interval of ≥1 week between each determination. The PSA value at screening must be ≥1 µg/L (1 ng/mL) if PSA is the only indication of progression; participants on systemic glucorticoids for control of symptoms must have documented PSA progression by PCWG3 criteria while on systemic glucocorticoids prior to commencing Cycle 1 Day 1 treatment.
- •Radiographic progression of soft tissue disease by RECIST 1.1 or bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
- •Participants must have FDHT lesion \>2 cm lesion that has an SUVmax of 2.9 or less in bone, or 2.4 or less in soft tissue, or two or more smaller lesions that meet those criteria.
Exclusion Criteria
- •Participant has received anti-cancer therapy (either approved or investigational) \< 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day
- •\< 42 days for prior nitrosureas or mitomycin C
- •Toxicities resulting from prior systemic cancer therapies must have resolved to ≤ NCI CTCAE Grade 1 prior to starting CC-90011 treatment (with exception of Grade 2 peripheral neuropathy and alopecia).
- •Previous anaphylactic reaction to either FDHT or FDG.
- •Participant has undergone major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to Cycle 1 Day 1 or who have not recovered from surgery.
- •Participant has completed any radiation treatment \< 4 weeks prior to Cycle 1 Day 1 or \< 2 weeks for palliative bone radiotherapy (single fraction). Participants with \> 25% of myelopoietic bone marrow radiation are not allowed to be enrolled on this study.
- •Participant has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management), or any other significant GI disorder that could affect the absorption of CC-
- •Participant with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
- •Participant with any hemorrhage/bleeding event \> CTCAE Grade 2 or haemoptysis \> 1 teaspoon within 4 weeks prior to the first dose
- •Symptomatic and untreated or unstable central nervous system (CNS) metastases or clinically significant spinal cord compression.
Arms & Interventions
CC-90011 in combination with Abiraterone and Prednisone
Oral administration (PO) of CC-90011 monotherapy administered once per week (QW), for 4 weeks. From cycle 2 onwards, all participants will receive 60 mg of CC-90011 PO QW, in combination with 100 mg of abiraterone PO daily, and 5 mg of prednisone PO every 12 hours (10mg QD)
Intervention: CC-90011
CC-90011 in combination with Abiraterone and Prednisone
Oral administration (PO) of CC-90011 monotherapy administered once per week (QW), for 4 weeks. From cycle 2 onwards, all participants will receive 60 mg of CC-90011 PO QW, in combination with 100 mg of abiraterone PO daily, and 5 mg of prednisone PO every 12 hours (10mg QD)
Intervention: Abiraterone
CC-90011 in combination with Abiraterone and Prednisone
Oral administration (PO) of CC-90011 monotherapy administered once per week (QW), for 4 weeks. From cycle 2 onwards, all participants will receive 60 mg of CC-90011 PO QW, in combination with 100 mg of abiraterone PO daily, and 5 mg of prednisone PO every 12 hours (10mg QD)
Intervention: Prednisone
Outcomes
Primary Outcomes
Assessment of androgen receptor (AR) level
Time Frame: From Screening to the end of cycle 3 (each cycle is 28 days)
FDG/FDHT PET imaging will be compared with Screening to Cycle 1 (each cycle is 28 days) and from Cycle 1 to Cycle 3 (Cycle 2-3 is combined therapy period) to assess changes in AR expression.
Secondary Outcomes
- Assessment of anti-tumor activity(Through study completion, Up to 3 years)
- Safety and tolerability assessed by dose-limiting toxicities (DLTs)(Through study completion, Up to 1.5 years)
- Safety and tolerability assessed by Adverse events (AEs)(From the time the subject signs the ICF until 90 days (± 3 days) after the last dose of study medication)