Status and phase
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About
This is an open-label, multicenter, non-randomized, dose-escalation phase 1 trial to evaluate the safety and tolerability of SHR3162 in participants with advanced solid tumors.
Full description
Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) is a family of proteins that plays important roles in multiple cellular processes, including single-strand DNA breaks, which if left unrepaired, leads to double-strand breaks (DSB) during DNA replication. The DSB can be repaired either through error-free homologous recombination (HR) or error-prone non-homology end joining. In HR deficient cancer cells with mutations on HR genes such as BRCA1, BRCA2 or partner and localizer of BRCA2 (PALB2), DSB cannot be efficiently and correctly repaired, resulting in cell death. Viable cells, on the other hand, have normal HR and do not replicate as often as cancer cells; thus they can survive PARP inhibition. PARP inhibitors are being actively developed worldwide as promising anti-tumor therapeutics. The current trial will be conducted in participants with advanced solid tumors for whom satisfactory treatments are not yet available.
In the dose-escalation phase, patients will be enrolled sequentially into the 8 dose levels of SHR3162 designated in this study(3-6 patients per cohort). One to two sentinel participants in Cohort 1 who will be treated and closely monitored for 24 hours. If no adverse effects are noted during the 24-hour period, dosing of further participants in the cohort may continue.
In the dose expansion part of the study, up to 12 additional participants will be enrolled at the MTD.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Males and/or females over age 18.
Ability to understand the purposes and risks of the trial and his/her signed informed consent form approved by Human Research Ethics Committee (HREC) of the trial site was obtained before the entering the trial.
Histologically or cytologically confirmed advanced or metastatic solid tumor for which no established standard therapy is available.
At least one measurable lesion by CT or MRI according to RECIST Version 1.1, which is not in irradiated area (only for expansion phase).
Recovered from toxicities of prior anti-cancer treatment to Grade 1 or less (in case of alopecia, Grade 2 is acceptable).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Life expectancy of at least 3 months.
Acceptable liver function defined below:
Acceptable renal function defined below:
Acceptable coagulation status defined below:
Acceptable hematologic status (without hematologic supports including hematopoietic factor, blood transfusion) defined below:
No clinically significant abnormalities in urinalysis.
Female participants of child bearing potential agree not to be pregnant or lactating during the study and for three months following the last dose of study drug. Both men and women of reproductive potential must agree to use a highly effective method of birth control during the study and for three months following the last dose of study drug. A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
30 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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