Entry Detail
| General information | |
| Database: | DB00556 |
| Objective: | The purpose of thisphase Ib study was to define the recommendedphase 2 dose of the combinations of gemcitabine and cisplatin or gemcitabine and carboplatin plus dovitinib. |
| Authors: | Galsky MD, et al |
| Title: | Phase Ib study of dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin in patients with advanced solid tumors. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2014 |
| PMID: | 25023489 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | dovitinib |
| Target: | Fibroblast growth factor receptor 3 Plateletderived growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | dovitinib + gemcitabine plus cisplatin or gemcitabine plus carboplatin |
| Study Type: | a singlecenter, nonrandomized, openlabelphase Ib trial |
| Key Patients Feature: | eligible patients were age more than and equal to 18 years with metastaticsolid tumors refractory to standard therapy or for whomgemcitabine plus cisplatin/carboplatin would constitute appropriate therapy. Patients had discontinued allprior chemotherapy and immunotherapy at least 4 weeksprior to enrollment and had a Karnofsky performancestatus of more than and equal to 70 %. required baseline laboratory valuesincluded absolute neutrophil count more than and equal to 1.5 ¡Á 109/l; platelets more than and equal to 125 ¡Á 109/l; hemoglobin more than and equal to 9 g/dl; serum creatinineclearance more than and equal to 60 ml/min or creatinine less than and equal to 1.5 for the cisplatin arm or a serum creatinine clearance more than and equal to 30 ml/min forthe carboplatin arm; bilirubin less than and equal to 1.5 ¡Á upper limit of normal (Uln); alanine transaminase and aspartate transaminase less than and equal to 1.5 ¡Á Uln; and a normal cardiac ejection fraction |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin |
| Treatment Info: | Treatment was administered with gemcitabine (1, 000 mg/m(2) on days 1 and 8), cisplatin (70 mg/m(2)), or carboplatin (AUC 5) on day 1, and dovitinib (orally on days 15, 812, and 1519), every 21 days. The starting dose of dovitinib was 300 mg and was dose escalated in successive cohorts using 3 + 3 dose escalation rules. |
| Primary End Point: | RP2D, pharmacokinetic, antitumor activity |
| Secondary End Point: | NA |
| Patients Number: | 14 |
| Trial Results | |
| DLT_MTD: | There were no protocoldefined doselimiting toxicities in the cisplatin arm.Two additional doselimiting toxicities (prolonged neutropenia and febrile neutropenia) occurred in the lotheyr dose cohort, and the study was closed. |
| Objective Response Rate: | No patients achieved an objective response to treatment. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | the most prominent adverse events in both the cisplatin and carboplatin arms were cytopenias: 64 % of patients experienced grade 3-4 neutropenia, and 36 % of patients experienced grade 3-4 thrombocytopenia. the remainder of the adverse events was consistent with the known side effect profiles of gemcitabine, cisplatin/carboplatin, and dovitinib. |
| Conclusions: | Dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin was poorly tolerated due to myelosuppression. |