Trial purpose
Cancer treatment
Tumor type
Genitourinary
Age
18+
Trial acronym
ATRIDIA SHR3680-002
Clinical summary
Summary
This study consists of 2 phases. In the dose escalation phase, up to 6 dose levels of SHR3680 (40 mg/day, 80 mg/day, 160 mg/day, 240 mg/day, 360 mg/day, 480 mg/day) will be investigated with a sequential "3+3" design (3 or 6 participants in each dose level). There will be a single-dose pharmacokinetic (PK) run-in period (7 days). Following the first dose, participants will enter a 1 week treatment-free period to evaluate safety and single-dose PK. If not dose-limiting toxicities (DLTs) are observed during the 1-week period, SHR3680 administration will resume at the same dose level. In the expansion phase, up to 12 additional participants will be enrolled at the MTD or recommended phase 2 dose (RP2D). The purpose of the expansion part of the study is to explore the clinical benefits of SHR3680 and to further identify its PK features.
Conditions
This trial is treating people with Prostate Cancer
Eligibility
Inclusion
- Male 18 years and older
- Ability to understand the purposes and risks of the trial and his/her signed informed consent form approved by the HREC of the trial site, which must be obtained before entering the trial
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
- Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the screening visit
- Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
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Progressive disease by PSA or imaging after docetaxel-based chemotherapy or abiraterone in the setting of medical or surgical castration. Prior enzalutamide is allowed as long as patients had a PSA response >50% or were treated for at least 6 months. Disease progression for study entry is defined by one or more of the following three criteria:
- PSA progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥2 μg/L (2 ng/mL)
- Soft tissue disease progression defined by RECIST (Appendix A)
- Bone disease progression defined by two or more new lesions on the bone scan
- ECOG performance status of 0 or 1
- Life expectancy of at least 6 months
- Able to swallow the study drug and comply with study requirements
-
Acceptable liver function defined as:
- Total bilirubin ≤ 1.5 times the upper limit of normal range (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times ULN; however, ≤ 5 times ULN in a subject who has liver metastases or has been treated with biliary drainage
-
Acceptable renal function defined below:
• Serum creatinine ≤ 1.5 times ULN
-
Acceptable hematologic status (without hematologic support including hematopoietic factor, blood transfusion) defined below:
- Absolute neutrophil count (ANC) ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 9.0 g/dL
Exclusion
- Treatment with AR antagonists (enzalutamide, bicalutamide, flutamide, nilutamide), 5-α reductase inhibitors (finasteride, dutasteride), estrogens, or chemotherapy within 4 weeks of enrollment (day 1 visit) or plans to initiate treatment with any of these drugs during the study. Ongoing therapy with bisphosphonates or Rank Ligand inhibitors are acceptable.
- Prior treatment with a PARP inhibitor or have plans to initiate treatment with a PARP inhibitor during the study (only apply to subjects participating in Part 2b)
- Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to initiate treatment with any of these therapies during the study
- Metastases in the brain or active epidural disease (Note: patients with treated for epidural disease are allowed to enter the trial)
- Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within 4 weeks of enrollment (day 1 visit) or plans to initiate treatment with any of these therapies during the study
- History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
- Radiation therapy within 3 weeks (if single fraction of radiotherapy, then a 1-week gap is allowable) and radionuclide therapy within 8 weeks of enrollment (Day 1 visit). Any radiotherapy-related AE > Grade 1 before the start of study treatment.
- Have used or plan to use from 30 days prior to enrollment (day 1 visit) through to the end of the study medications known to lower the seizure threshold or prolong the QT-interval (described in Appendix I)
- Cardiac disease with New York Heart Association (NYHA) Class III or IV, including congestive heart failure, myocardial infarction within 6 months prior to the trial entry, unstable arrhythmia, or symptomatic peripheral arterial vascular disease
- Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
- History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack within 12 months of enrollment (day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)
- Use of an investigational agent within 4 weeks of enrollment or plans to initiate treatment with an investigational agent during the study
- Major surgery, other than diagnostic surgery, within 4 weeks prior to trial entry, without complete recovery
- Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within the last 3 months)
- Structurally unstable bone lesions suggesting impending fracture
Inclusion
- You are able to swallow medication by mouth.
- You have had a certain type of treatment or surgical procedure.
- Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
- You are currently being treated on a clinical trial.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
Atridia Pty Ltd.
Scientific Title
A Phase 1 Trial of SHR3680 in Subjects With Metastatic Castration-Resistant Prostate Cancer as Monotherapy
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