Advanced Metastatic Castration Resistant Prostate Cancer
Conditions
Keywords
mCRPC, Prostate Cancer
Brief summary
This is a Phase 1 and Phase 2 study to evaluate the safety and antitumor activity of INV-9956 in adult patients with advanced metastatic Castration Resistant Prostate Cancer.
Detailed description
This is a Phase 1 and Phase 2 study to evaluate the safety and antitumor activity of INV-9956 in adult patients with advanced metastatic Castration Resistant Prostate Cancer. The entire study consists of two parts: Phase 1 for dose escalation and Phase 2 for dose expansion. Phase 1 dose escalation of INV-9956 follows a real time monitored, PK/PD and safety guided scheme with a traditional 3+3 design for DLT assessment. Phase 2 aims to reassure the safety profile and better define efficacy. Phase 2 consists of up to 2 cohorts by different AR gene status: * Cohort A: AR mutant CRPC * Cohort B: AR wide-type CRPC (optional) Currently enrolling patients under Phase 2.
Interventions
DRUGINV-9956
INV-9956 is co-administered with dexamethasone and fludrocortisone acetate
Sponsors
Shenzhen Ionova Life Sciences Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained. 2. Male aged ≥ 18 years. 3. Histologically confirmed adenocarcinoma of the prostate. 4. Castration resistant prostate cancer with serum testosterone \<50 ng/dL. 5. Metastatic disease. 6. Ongoing androgen deprivation therapy with GnRH analogue or antagonist, or have had bilateral orchiectomy. 7. Received at least one prior line of taxane-based chemotherapy and at least one line of hormonal AR targeted therapy (eg, abiraterone, enzalutamide). Patients who have refused or were intolerant to taxane-based chemotherapy may be enrolled. 8. ECOG performance status 0-1. 9. Adequate marrow, liver and kidney function. 10. INR ≤1.5. 11. Able to swallow study treatment. 12. Has a life expectancy of \> 3 months.
Exclusion criteria
1. Have a medical condition such as Crohn's disease or have undergone significant surgery to the gastrointestinal tract that could impair absorption or that could result in short bowel syndrome with diarrhea due to malabsorption. 2. History of pituitary or adrenal dysfunction. 3. Poorly controlled diabetes mellitus. 4. Clinically significant abnormality in serum potassium and sodium. 5. Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor. 6. Active or unstable cardio-/cerebro-vascular disease, including thromboembolic events. 7. History of congestive heart failure; cardiac disease, myocardial infarction within 6 months prior to enrollment. 8. Prolonged QTcF interval. 9. Active infection or other medical condition that would make corticosteroid contraindicated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximum tolerated dose (MTD) | Within first 28 days of treatment | The highest dose level at which at least 6 patients have been treated and less than 33% of patients experienced a DLT. |
| Phase 1: Recommended dose range (RDR) | 12 months | The RDR will be determined based on the PK and PD data, the preliminary clinical activity of INV-9956, as well as the incidence rate and nature of the toxicities observed in subsequent cycles beyond Cycle 1 |
| Phase 2: Evaluate Radiographic progression-free survival (rPFS) | 12 months | To evaluate rPFS per PCWG-modified RECIST v1.1 (soft tissue response) and PCWG3 criteria (bone metastases) |
| Phase 2: Evaluate overall response rate (ORR) | 12 months | To evaluate ORR per PCWG-modified RECIST v1.1 (soft tissue response) and PCWG3 criteria (bone metastases) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Characterize the safety of INV-9956 as assessed by CTCAE v5.0 | 12 months | To analyze the safety profile of INV-9956 as a single agent by AE, clinical lab test results, ECG and Vital signs changes |
| Phase 1: Determine the PK using AUC of INV-9956 | 12 months | To determine the pharmacokinetics (PK) using AUC of INV-9956 after a single dose and at steady state after multiple doses |
| Phase 1: Determine the PK using Cmax of INV-9956 | 12 months | To determine the pharmacokinetics (PK) using Cmax of INV-9956 after a single dose and at steady state after multiple doses |
| Phase 1: Determine the blood concentration of steroid hormone | 12 months | To determine the blood concentration of steroid hormones at various timepoints as PD markers for INV-9956 |
| Phase 1: Evaluate Radiographic progression-free survival (rPFS) | 12 months | To evaluate rPFS per PCWG-modified RECIST v1.1 (soft tissue response) and PCWG3 criteria (bone metastases) |
| Phase 1: Evaluate overall response rate (ORR) | 12 months | To evaluate ORR per PCWG-modified RECIST v1.1 (soft tissue response) and PCWG3 criteria (bone metastases) |
| Phase 2: Characterize the safety of INV-9956 as assessed by CTCAE v5.0 | 12 months | To analyze the safety profile of INV-9956 as a single agent by AE, clinical lab test results, ECG and Vital signs changes |
| Phase 2: Determine the PK using AUC of INV-9956 | 12 months | To determine the pharmacokinetics (PK) using AUC of INV-9956 after a single dose and at steady state after multiple doses |
| Phase 2: Determine the PK using Cmax of INV-9956 | 12 months | To determine the pharmacokinetics (PK) using Cmax of INV-9956 after a single dose and at steady state after multiple doses |
| Phase 2: Determine the blood concentration of steroid hormone | 12 months | To determine the blood concentration of steroid hormones at various timepoints as PD markers for INV-9956 |
Countries
China, United States
Contacts
CONTACTYi Zhu, MD, MBA
Outcome results
None listed