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This is a Phase I, first-in-human, open-label, dose-escalation study of IMP4297 administered orally once every day to patients with advanced solid tumors for whom standard therapy either does not exist or has proven to be ineffective or intolerable. Patients with advanced breast cancer, ovarian cancer or prostate cancer are preferred. There are two stages to this study: a dose-escalation stage and a dose-expansion stage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IMP4297 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IMP4297 | Drug | The dose levels will be escalated following a modified 3+3 dose escalation scheme. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The AEs (adverse event) of single and multiple doses of IMP4297 administered to participants with advanced solid tumors. | Evaluate the TEAE (treatment-emergent adverse event) of IMP4297 | Each visit after IMP4297 administrated (through study completion, an average of 10 months) |
| The maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLTs) of IMP4297 | Evaluate DLT and determine the MTD | Within 28 days after IMP4297 administrated |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under Curve [AUClast, AUCINF] | Within 7 days after firstly single dose administrated | |
| Area Under Curve [AUClast, AUCINF] | Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) |
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Inclusion Criteria:
Exclusion Criteria:
Inadequate hematologic and organ function, defined by the following (hematologic parameters must be assessed ≥14 days after a prior treatment, if any):
The INR applies only to patients who do not receive therapeutic anti-coagulation.
Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, radiotherapy within 4 weeks prior to initiation of study treatment with the following exceptions:
Adverse events from prior anti-cancer therapy that have not resolved to NCI CTCAE Grade ≤ 1, except for alopecia.
Prior therapies targeting PARP (poly-ADP ribose polymerase).
Clinical significant active infection
Known clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
Known human immunodeficiency virus infection
New York Heart Association Class II or greater congestive heart failure; history of myocardial infarction or unstable angina within 6 months prior to Day 1; history of stroke or transient ischemic attack within 6 months prior to Day 1
Active or untreated brain metastasis
Pregnant (positive pregnancy test) or lactating women
Male or female patients of child-producing potential unwilling to use double barrier contraception: condoms, sponge, foams, jellies, diaphragm or intrauterine device, contraceptives (oral, injectable or parenteral), implanon, or other avoidance of pregnancy measures during the study and for 90 days after the last day of treatment
Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
Inability to comply with study and follow-up procedures
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
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| Name | Affiliation | Role |
|---|---|---|
| BingHe Xu, Doctor | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Principal Investigator |
| JunNing Cao, Doctor | Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Hospital Chinese Academy of Medical Sciences | Beijing | Beijing Municipality | 100021 | China | ||
| Fudan University Shanghai Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37338150 | Derived | Cao J, Guo H, Ji D, Shen W, Zhang S, Hsieh CY, Xiong Cai S, Edward Tian Y, Xu C, Zhang P, Xu B. Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors: A Phase I Trial. Oncologist. 2023 Dec 11;28(12):e1259-e1267. doi: 10.1093/oncolo/oyad163. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D010051 | Ovarian Neoplasms |
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C000729920 | senaparib |
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| Maximum plasma concentration (Cmax) | Within 7 days after firstly single dose administrated |
| Maximum plasma concentration (Cmax) | Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) |
| Time at which Cmax occurred (Tmax) | Within 7 days after firstly single dose administrated |
| Time at which Cmax occurred (Tmax) | Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) |
| Trough Concentrations (Ctrough) | Within 7 days after firstly single dose administrated |
| Trough Concentrations (Ctrough) | Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) |
| Clearance (CL/F) | Within 7 days after firstly single dose administrated |
| Clearance (CL/F) | Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) |
| Volume of distribution (Vd/F) | Within 7 days after firstly single dose administrated |
| Volume of distribution (Vd/F) | Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) |
| Shanghai |
| Shanghai Municipality |
| 200032 |
| China |
| D017437 |
| Skin and Connective Tissue Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D005834 | Genital Neoplasms, Male |
| D005832 | Genital Diseases, Male |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |