Entry Detail
| General information | |
| Database: | DB00693 |
| Objective: | To determine if intrapatient dose escalation of the multitargeted kinase inhibitor sorafenib is feasible in patients with advanced pretreated solid malignancies. |
| Authors: | Semrad TJ, et al |
| Title: | Feasibility study of intrapatient sorafenib doseescalation or reescalation in patients with previously treated advanced solid tumors. |
| Journal: | Invest New Drugs |
| Year: | 2012 |
| PMID: | 22015991 |
| Trial Design | |
| Clinical Trial Id: | NCT00810394 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | PHASE II STUDy |
| Key Patients Feature: | Patients aged 18 years and older with refractory solidtumors were eligible. Patients with measurable or nonmeasurable disease on imaging studies performed within28 days of registration were eligible and were required tohave an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Any number of prior treatmentswas allowed, as long as treatment was completed at least2 weeks prior to registration and all toxicities had resolvedto grade 1 or less. Further inclusion criteria included abilityto give informed consent, ability to take oral medication, and acceptable endorgan function defined by an absoluteneutrophil countmore than and equal to 1, 500/mm3, hemoglobinmore than and equal to 9.0 g/dl, platelet countmore than and equal to 100, 000/mm3, total bilirubinless than and equal to 1.5 times the upperlimit of normal (ULN), ALT and ASTless than and equal to 2.5 times the ULN(less than and equal to 5 x ULN for patients with liver involvement), andcreatinineless than and equal to 1.5 times ULN. Patients on warfarin or lowmolecular weight heparin treatment were allowed providedwere on a stable dose and had no evidence of bleeding |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | An intrapatient dose escalation scheme starting at 400 mg BID was employed in this prospective trial. Doses were escalated to 600 mg BID for the second cycle and to 800 mg BID for the third cycle in the absence of grade 3+ adverse events. In the event of grade 3+ adverse events during cycle 1, doses were reduced to 400 mg daily through cycle 2. Dose reescalation for cycle 3 was allowed in the absence of grade 3+ adverse events during cycle 2. Further dose escalation was prohibited. |
| Primary End Point: | the overall percentage of patients tolerating dose escalation to 600 mg BID through cycle 2 or tolerating reescalation to 400 mg BID through cycle 3 |
| Secondary End Point: | NA |
| Patients Number: | 50 |
| Trial Results | |
| DLT_MTD: | Common grade 3+ adverse events included handfootskin reaction, hypertension, and hypophosphatemia. |
| Objective Response Rate: | Of the 34 patients who wereevaluable for treatment response by RECIST, no responseswere observed. The best overall response was stable disease in 38% of evaluable patients. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.7 months (95% C.I. 4.3-6.1 months). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common grade 3+ adverse events included handfoot skin reaction, hypertension, and hypophosphatemia. Conclusions Intrapatient dose escalation and/or reescalation of sorafenib were not feasible in pretreated solid tumor patients. |
| Conclusions: | Intrapatient dose escalation andor reescalation of sorafenib were not feasible in pretreated solid tumor patients. Sorafenib dose escalation remains an investigational approach. |