| General information |
| Database: | DB00697 |
| Objective: | They assessed the maximal tolerated dose (MTD), evaluated the pharmacokinetics and preliminary antitumour efficacy of oral SU014813 administered continuously in combination with docetaxel to patients with advanced solid tumours. |
| Authors: | de Jonge MJ, et al |
| Title: | Phase I safety and pharmacokinetic study of SU014813 in combination with docetaxel in patients with advanced solid tumours. |
| Journal: | Eur J Cancer. |
| Year: | 2011 |
| PMID: | 21439816 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | SU014813
|
| Target: | VEGFR2, PDGFR¦Â and FLT3ITD phosphorylation
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced and measurable or evaluable solid tumour(GIST Melanoma) |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | SU014813+docetaxel |
| Study Type: | Phase I safety and pharmacokinetic study |
| Key Patients Feature: | Patients with a cytologically or histologically confirmeddiagnosis of an advanced and measurable or evaluable solidtumour were eligible. Additional criteria included: age P18 years; ECOG performance status 0 or 1; an adequate bonemarrow function (haemoglobin P 10 g/dL, platelet count P100 . 109/L, absolute neutrophil count P 1.5 . 109/L), liverfunction (bilirubin 6 1.5 the upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase 6 2.5 . ULN (5 . ULN in case of liver metastasis in thepresence of a normal alkaline phosphatase), alkaline phosphatase 6 2.5 . ULN (5 . ULN in case of bone or liver metastasis in the presence of a normal ALT/AST)) and renal function(serum creatinine 6 1.5 . ULN) and a serum albumin P3.0 g/dL. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | In thisphase I study successive patient cohorts received docetaxel 60 or 75mg/m(2) every 3weeks in combination with chronic daily dosing of SU014813. Dose limiting toxicity was assessed both in the first and second treatment cycle. |
| Primary End Point: | maximal tolerated dose (MTD) |
| Secondary End Point: | (a) evaluation of pharmacokinetics drug interactions between SU014813 and docetaxel and (b) to assess antitumour effects induced by the combination in the patients with measurable disease. |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | Dose limiting toxicities were prolonged neutropenia, neutropenic fever, fatigue and diarrhoea.Other toxicities included fatigue, alopecia, nausea, vomiting, anorexia, rash, hypertensionand hair discolouration. The recommendedphase II dose was determined to be docetaxel75 mg/m2 in combination with SU014813 50 mg/day |
| Objective Response Rate: | Two patients (8%) achieved a partial response (PR) and 7patients (29%) had stabilisation of their disease (SD) >6 months, for a clinical benefit rate of37.5% |
| Disease Control Rate: | 0.37 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Dose limiting toxicities were prolonged neutropenia, neutropenic fever, fatigue and diarrhoea. Other toxicities included fatigue, alopecia, nausea, vomiting, anorexia, rash, hypertension and hair discolouration. |
| Conclusions: | Oral SU014813 50mgday with docetaxel 75mg/m(2) is a clinically feasible regimen with a manageable safety profile and antitumour activity. Further development is warranted in patients with melanoma and GIST. |