Clinical trial NCT06130995: Relugolix + Enzalutamide Study in High-Risk Prostate Cancer
Official title: Phase IB Trial of Relugolix and Enzalutamide as Neoadjuvant/ Adjuvant to Local-regional Treatment in Patients With High-risk Locally Advanced Prostate CAncer (RENAPCA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Androgen Deprivation Therapy
Locally Advanced Prostate Cancer
Keywords: dose limiting toxicity (DLTs)
pathologic complete response (pCR)
minimal residual disease (MRD)
radiation therapy (RT)
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Astellas Pharma Inc
First posted: 2023-11-14
Enrollment: 46
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: This is a single arm phase Ib study with safety lead-in cohorts to investigate the efficacy and safety of neoadjuvant and adjuvant hormonal therapy with relugolix plus enzalutamide in patients with high-risk locally advanced prostate cancer who are candidates for ADT followed by definitive radiation therapy (RT) or surgical treatment.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test how effective and safe it is to use a combination of two medications, relugolix and enzalutamide, in patients with advanced prostate cancer. We want to see if this combination can help improve the chances of curing the cancer and make the patients live longer without the cancer getting worse.

The main questions we want to answer in this study are:

* Can using relugolix and enzalutamide together help increase the chances of curing high-risk advanced prostate cancer?
* Does this combination treatment help patients live longer without their cancer getting worse?

Participants in this study will be asked to take relugolix and enzalutamide as part of their cancer treatment. They will also undergo Radiation Therapy or prostatectomy, which are standard treatments for this type of cancer.

Detailed description: This clinical trial aims to assess the effectiveness and safety of combining relugolix and enzalutamide as neoadjuvant and adjuvant androgen deprivation therapy (ADT) in patients diagnosed with high-risk locally advanced prostate cancer who are also candidates for definitive radiation therapy (RT) or surgical treatment. The objectives of this phase Ib clinical trial are to evaluate the efficacy, safety, and dynamic changes in biomarkers associated with this combination therapy. A combined total of up to 41 evaluable patients will participate in this study, with the initial safety lead-in cohorts involving a potential enrollment of 12 patients, followed by a dose expansion cohort that may include up to 29 subjects.

The combined treatment cycle spans 28 days, with patients receiving six months of neoadjuvant therapy followed by an additional 18 months in the adjuvant setting. Treatment duration may be shortened if unacceptable toxicity occurs or if a patient withdraws consent. Approximately 24 months of post-accrual follow-up are anticipated to adequately assess the efficacy and safety of the treatment.

Ultimately, the study aims to contribute valuable insights into the potential benefits of neoadjuvant and adjuvant hormonal therapy with relugolix plus enzalutamide in improving outcomes for patients facing high-risk locally advanced prostate cancer.

Eligibility criteria: Inclusion Criteria:

1. Capable of giving signed informed consent;
2. Patients must be ≥18 years of age at the time of signing the informed consent form.
3. Men with a diagnosis of adenocarcinoma of the prostate pathologically proven diagnosis with the following:

   • Locally advanced high-risk prostate defined as i. PSA \>20 ng/mL or ISUP grade 4/5 (Gleason score \>7) or cT2c or ii. Any PSA, any ISUP grade, cT3-4 or cN+ (locally advanced)
4. Have normal organ and bone marrow function measured at the screening visit including

   * Platelets ≥100 × 103/microliter (μL);
   * Hemoglobin ≥ 10.0 grams/dL;
   * Leukocytes (WBC) ≥ 3 × 103/μL;
   * Absolute neutrophil count ≥1.5 × 103/μL;
   * Serum AST and ALT ≤2.5 × upper limit of normal (ULN);
   * Total bilirubin ≤1.5 ×ULN (unless values are consistent with Gilbert's syndrome for which the total bilirubin must be \< 3x ULN);
   * Serum creatinine ≤ 1.5 × ULN; OR Measured or calculated creatinine clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
6. The participant has, in the opinion of the investigator, a life expectancy of at least 6 months.
7. Male patients must be willing to use contraception during treatment and for 3 months after the last dose of study treatment when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.

Exclusion Criteria:

1. History of major adverse cardiac event, including myocardial infarction, new congestive heart failure (CHF) or CHF exacerbation, or stroke, within the past 6 months.
2. Patients who are receiving any other investigational agents.
3. Patients with distant metastatic cancer will be excluded from the study as intermittent hormonal therapy is not standard of care treatment for this population.
4. Active secondary malignancies requiring treatment
5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of study drugs
6. Participants with uncontrolled intercurrent illness.
7. Participant is unable to swallow pills.
8. Not a candidate for surgical or radiation therapy

Primary outcomes:
measure: Proportion of patient experiencing dose limiting toxicity (DLT) and tolerable dose of relugolix and enzalutamide combination
timeFrame: 2-3 years
measure: Proportion of patients experiencing Pathologic Complete Response (pCR) and Minimal Residual Disease (MRD) in Neoadjuvant ADT with the combination of Relugolix and Enzalutamide
timeFrame: 4-6 years
Secondary outcomes:
measure: Objective response rate (ORR) of neoadjuvant ADT of relugolix and enzalutamide
timeFrame: 4-6 years
measure: Frequency and severity of adverse events of relugolix and enzalutamide
timeFrame: 4 years
measure: Prostate specific antigen (PSA) response to the combination of relugolix and enzalutamide
timeFrame: 4 years
measure: Diagnostic precision and constraints of biopsy in assessing positive margin rates and rates of pathologic downgrade.
timeFrame: 4-6 years
measure: Progression-Free Survival (PFS) in Patients Receiving Neoadjuvant Relugolix and Enzalutamide
timeFrame: 4-6 years
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center at OU Health, University of Oklahoma Health Sciences Center (SCC-OUHSC)
state: Oklahoma
Study officials:
References: