Outcomes
DLTs, neutropenia, diarrhea, fever, Tumor, cancer, toxicities, thrombocytopenia, nausea, vomiting
UNCONTROLLED HYPERTENSION, NEUTROPENIA, TUMOR, GYNECOLOGIC CANCER, CANCER, DISEASE, THROMBOCYTOPENIA, ELECTROLYTE DISORDER, DISEASE
The primary endpoint was to determine the recommended phase 2 dose (RP2D) and tolerability of the fuzuloparib-apatinib combination. Secondary endpoints included best overall response, objective response rate (ORR) and disease control rate (DCR) per RECIST v1.1, cancer antigen 125 (CA-125) response, PFS, overall survival, and PK parameters.Safety was monitored using AEs, laboratory tests and clinical examinations. AEs were graded according to CTCAE v4.03. DLTs were assessed from the first dose of study treatment (cycle 0 day 1) to the end of cycle 1 of the combination therapy (34 days in total), and defined as any of the following treatment-related AEs (TRAEs): non-hematologic toxicities of grade 3 or worse (with the exception of well-managed grade 3 nausea, vomiting, or diarrhea, and grade 3 creatinine or electrolyte disorder which resolved to grade 1 or baseline level within 24 h), uncontrolled hypertension of grade 3 or worse, grade 4 neutropenia or grade 3 neutropenia accompanied by fever (≥ 38.5 °C), grade 4 thrombocytopenia and toxic effects resulting in dose delay for ≥ 14 days.Tumor response was assessed using CT or MRI at baseline and every 2 cycles per RECIST v1.1. A complete response (CR) or partial response (PR) was confirmed with a subsequent scan at least 4 weeks after the initial documentation. Disease evaluations based on CA-125 were performed according to the Gynecologic Cancer Intergroup (GCIG) criteria. CA-125 response, defined as a reduction of ≥ 50% in CA-125 level, was assessed in patients with CA-125 levels ≥ 2 folds of the normal upper limit at baseline; the response was confirmed by repeat testing at least 4 weeks apart.Pharmacokinetic sampling for single dose of fuzuloparib and apatinib was done on day 1 and day 4 (pre-dose and 0.5, 1, 2, 3, 4, 8, 12, 24, 48 h post-dose) of cycle 0, respectively; sampling for continuous dosing of the combination therapy was done on days 1 (pre-dose and 0.5, 1, 2, 3, 4, 8, 12, 24 h post-dose), 8 (pre-dose), 15 (pre-dose), 22 (pre-dose) of cycle 1, and day 1 (pre-dose and 0.5, 1, 2, 3, 4, 8, 12, 24 h post-dose) of cycle 2.