Clinical Trials /

A Study of CC-90011 and Comparators in Participants With Prostate Cancer

NCT04628988

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CC-90011 and Comparators in Participants With Prostate Cancer
  • Official Title: A Phase 1, Open-label, Functional Imaging Study to Assess Whether CC-90011 Reverses the Castration Resistance Due to Lineage Switch in Participants 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

Clinical Trial IDs

  • ORG STUDY ID: CC-90011-PCA-001
  • SECONDARY ID: U1111-1257-9342
  • NCT ID: NCT04628988

Conditions

  • Prostatic Neoplasms

Interventions

DrugSynonymsArms
CC-90011CC-90011 in combination with Abiraterone and Prednisone
AbirateroneZytigaCC-90011 in combination with Abiraterone and Prednisone
PrednisoneDeltasoneCC-90011 in combination with Abiraterone and Prednisone

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CC-90011 in combination with Abiraterone and PrednisoneExperimentalOral 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)
  • CC-90011
  • Abiraterone
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          1. Participant is a male ≥ 18 years of age the time of signing the informed consent form
             (ICF).

          2. Histologically confirmed adenocarcinoma of the prostate.

          3. 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

               -  Has completed at least 12 weeks of prior continuous therapy with enzalutamide.

               -  Has not been without enzalutamide treatment for >15 days prior to initiation of
                  study treatment.

          4. Participants who have received abiraterone prior to enzalutamide are eligible.

          5. One to two line(s) of prior taxane-based chemotherapy are allowed. If docetaxel
             chemotherapy is used more than once, this will be considered as one regimen.

          6. 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.

          7. 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.

          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.

          9. Participants must have the following laboratory values:

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7
                  days (14 days if participant received pegfilgastrim)

               -  Hemoglobin (Hgb) ≥ 9 g/dL (≥ 90 g/L or > 5.59 mmol/L)

               -  Platelet count (plt) ≥ 100 x 109/L

               -  Serum potassium concentration within normal range, or correctable with
                  supplements

               -  Serum AST/SGOT and ALT/SGPT ≤ 3.0 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if
                  liver metastases are present

               -  Serum total bilirubin ≤ 1.5 x ULN (≤ 2 x ULN in case of documentened Gilbert).

               -  Participants must have serum albumin ≥ 3.0 g/dL

               -  Serum creatinine ≤ 1.5 x ULN, or measured glomerular filtration rate (GFR) ≥ 60
                  mL/min/1.73m2 using an exogenous filtration marker such as iohexol, inulin, 51Cr
                  EDTA or 125I iothalamate. In cases where the serum creatinine is < 1,5xULN, there
                  is no need to calculate GFR.

               -  PT (or INR) and activated partial thromboplastin time (APTT)

                    1. within normal range (Part A)

                    2. ≤1.5 ULN

        Exclusion Criteria:

          1. Participant has received anti-cancer therapy (either approved or investigational) ? 4
             weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.

             - < 42 days for prior nitrosureas or mitomycin C

          2. 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).

          3. Previous anaphylactic reaction to either FDHT or FDG.

          4. 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.

          5. 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.

          6. 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-90011.

          7. Participant with symptomatic or uncontrolled ulcers (gastric or duodenal),
             particularly those with a history of and/or risk of perforation and GI tract
             hemorrhages.

          8. Participant with any hemorrhage/bleeding event > CTCAE Grade 2 or haemoptysis > 1
             teaspoon within 4 weeks prior to the first dose

          9. Symptomatic and untreated or unstable central nervous system (CNS) metastases.

               -  Participant recently treated with whole brain radiation or stereotactic
                  radiosurgery for CNS metastases must have completed therapy at least 4 weeks
                  prior to Cycle 1, Day 1 and have a follow-up brain computed tomography (CT) or
                  magnetic resonance imaging (MRI) demonstrating either stable or improving
                  metastases 4 or more weeks after completion of radiotherapy (the latter to be
                  obtained as part of the Screening Assessments, refer to Section 6.1)

               -  Participant must be asymptomatic and off steroids or on stable dose of steroids
                  for at least 4 weeks (?10 mg/day prednisone equivalent)

         10. Participant has known symptomatic acute or chronic pancreatitis.

         11. Participant with severe hepatic impairment (Child-Pugh Class C).

         12. Abiraterone with prednisone is contraindicated in combination with Ra-223.

         13. Medical castration with LHRH analogue is not permitted at any time during treatment
             with abiraterone and prednisone if not started at least 4 weeks prior to Cycle 2 Day
             1.

         14. Participant has impaired cardiac function or clinically significant cardiac diseases,
             including any of the following:

               -  LVEF < 45% as determined by multiple gated acquisition scan (MUGA) or
                  echocardiogram (ECHO)

               -  Complete left bundle branch or bifascicular block

               -  Congenital long QT syndrome

               -  Persistent or clinically meaningful ventricular arrhythmias or atrial
                  fibrillation.

               -  QTcF ≥ 450 msec on Screening ECG (mean of triplicate recordings)

               -  Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting
                  CC-90011

         15. Participant has other clinically significant heart disease such as congestive heart
             failure requiring treatment or uncontrolled hypertension (blood pressure ? 160/95 mm
             Hg).

         16. Participants who are known to be human immunodeficiency virus (HIV) positive with an
             acquired immunodeficiency syndrome (AIDS) defining opportunistic infection within the
             last year, a detectable viral load, or a current CD4 count < 350 cells/uL.

         17. Participant has untreated chronic hepatitis B or chronic hepatitis B virus (HBV)
             carriers with HBV DNA > 500 IU/mL (2500 copies/mL), or active hepatitis C. Inactive
             hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA
             < 500 IU/mL), and cured hepatitis C participants can be enrolled.

         18. Participant with ongoing treatment with chronic, therapeutic dosing of anticoagulants
             (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors, thrombin
             antagonist). Low dose low molecular weight heparin for catheter maintenance and for
             short-term prophylaxis for participants with prior pulmonary embolism (PE) and deep
             vein thrombosis (DVT) are permitted under careful consideration by the Investigator.

         19. Participant has a history of concurrent second cancers requiring active, ongoing
             systemic treatment.

         20. Participant has any significant medical condition (eg, active or uncontrolled
             infection or renal disease), laboratory abnormality, or psychiatric illness that would
             prevent the participant from participating (or compromise compliance) in the study or
             would place the participant at unacceptable risk if he/she were to participate in the
             study.

         21. Participants with poor bone marrow reserve as assessed by Investigator such as in the
             following conditions of:

               -  Having received extensive bone radiotherapy

               -  Having experienced several episodes of bone marrow aplasia in previous treatments

               -  Requiring regular hematopoietic support (blood transfusion, erythropoietin, GCSF)

         22. Participant has any condition that confounds the ability to interpret data from the
             study.

         23. Participant does not tolerate the study drug components.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of androgen receptor (AR) level
Time Frame:From Screening to the end of cycle 3 (each cycle is 28 days)
Safety Issue:
Description: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 Outcome Measures

Measure:Safety and tolerability assessed by Adverse events (AEs)
Time Frame:From the time the subject signs the ICF until 90 days (± 3 days) after the last dose of study medication
Safety Issue:
Description:All AEs will be monitored and recorded from the time the subject signs the ICF until 90 days (± 3 days) after the last dose of study medication. For SAEs made known to the Investigator at any time thereafter that are suspected of being related to study drug, must be reported. For subjects who have high blood pressure related to abiraterone treatment, blood pressure monitoring every 2 weeks should continue after discontinuation of abiraterone until the blood pressure normalizes or returns to pre-enrollment levels.
Measure:Safety and tolerability assessed by dose-limiting toxicities (DLTs)
Time Frame:Through study completion, Up to 1.5 years
Safety Issue:
Description:DLTs will be assessed using the NCI CTCAE criteria, version 5.0. An event will be considered a DLT if the event is attributed (definitely, probably or possibly) to study treatment during Cycle 2 (4weeks) consistent with CC-90011 in combination with abiraterone and prednisone
Measure:Assessment of anti-tumor activity
Time Frame:Through study completion, Up to 3 years
Safety Issue:
Description:Anti-tumor activity will be assessed based on Prostate Cancer Clinical Trials Working Group (PCWG3) criteria

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • mCRPC
  • AR
  • enzalutamide
  • abiraterone
  • LSD1
  • Prostate Cancer
  • CC-90011
  • Prednisone

Last Updated

November 16, 2020