Entry Detail
| General information | |
| Database: | DB00830 |
| Objective: | The maximum tolerated dose (MTD) and overall safety of sunitinib plus pemetrexed and carboplatin was determined in patients with advanced solid malignancies |
| Authors: | Blais N, et al |
| Title: | Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignanciesresults of a phase I doseescalation study. |
| Journal: | Invest New Drugs. |
| Year: | 2013 |
| PMID: | 23963796 |
| Trial Design | |
| Clinical Trial Id: | NCT00528619 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Sunitinib combined with pemetrexed + carboplatin |
| Study Type: | phase I doseescalation study |
| Key Patients Feature: | Patients aged 18 years or older with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were enrolled. Patients had a histologic or cytopathologic diagnosis of solid malignancy refractory to standard therapy or for which no standard therapy existed, adequate organ function (including bone marrow, kidney, and liver), and a life expectancy of more than and equal to 12 weeks. In the expansion cohort, previously treated and/or platinum refractory/intolerant patients with recurrent or advanced non small cell lung cancer of any histologic subtype and patients with advanced unresectable mesothelioma (pleural or peritoneal; stage 3 or 4) were eligible for enrollment. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients received oral sunitinib on a continuous daily dosing (CDD) schedule (37.5 mg/day) or Schedule 2/1 (2 weeks on treatment, 1 week off treatment; 37.5 or 50 mg/day). Pemetrexed (400500 mg/m(2) IV) and carboplatin (AUC = 5 mg.min/ml IV) were administered q3w. At the MTD for the chosen schedule, a cohort of patients with non small cell lung cancer (non small cell lung cancer) or mesothelioma was further evaluated. |
| Primary End Point: | The maximum tolerated dose (MTD) and overall safety |
| Secondary End Point: | NA |
| Patients Number: | 21 |
| Trial Results | |
| DLT_MTD: | The MTD was defined as the highest dose at which 0/3 or less than and equal to 1/6 patients experienced a doselimiting toxicity (DLT) during the first 22 days of treatment, with the next higher dose level having at least 2/3 or 2/6 patients with a DLT. DLTs were defined as grade 3 or 4 drugrelated toxicities that occurred during the defined time frame or that resulted in a delay in administering cycle 2. Hematologic DLTs were defined as neutropenia (grade more than and equal to 3 with grade more than and equal to 3 infection; grade 4 lasting more than and equal to 7 days or with fever >38.5 ¡ãC lasting >24 h), thrombocytopenia (grade more than and equal to 3 with bleeding or grade 4 for more than and equal to 7 days), or lymphopenia accompanied by an opportunistic infection. Nonhematologic DLTs included grade 3/4 toxicities lasting more than and equal to 7 days. Nausea, vomiting, and diarrhea that persisted at grade 3/4 despite maximal medical therapy were also considered DLTs.The MTD was defined as the highest dose at which 0/3 or less than and equal to 1/6 patients experienced a doselimiting toxicity (DLT) during the first 22 days of treatment, with the next higher dose level having at least 2/3 or 2/6 patients with a DLT. DLTs were defined as grade 3 or 4 drugrelated toxicities that occurred during the defined time frame or that resulted in a delay in administering cycle 2. Hematologic DLTs were defined as neutropenia (grade more than and equal to 3 with grade more than and equal to 3 infection; grade 4 lasting more than and equal to 7 days or with fever >38.5 ¡ãC lasting >24 h), thrombocytopenia (grade more than and equal to 3 with bleeding or grade 4 for more than and equal to 7 days), or lymphopenia accompanied by an opportunistic infection. Nonhematologic DLTs included grade 3/4 toxicities lasting more than and equal to 7 days. Nausea, vomiting, and diarrhea that persisted at grade 3/4 despite maximal medical therapy were also considered DLTs. |
| Objective Response Rate: | 19.00% |
| Disease Control Rate: | 42.90% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Overall survival times were greater than 10.0, 6.9, and 10.6 months (all 3 patients were alive at last data collection point). |
| Adverse Event(agent arm): | Among patients in the expansion cohort, fatigue/asthenia (n = 6; 100 %), nausea, and decreased appetite (each n = 5; 83 %) were most common. Hematologic laboratory abnormalities on Schedule 2/1 at the MTD were grade 3/4 neutropenia, n = 5 (83 %); grade 3 leukopenia, n = 5 (83 %); grade 3 lymphopenia, n = 1 (17 %); grade 3/4 thrombocytopenia, n = 3 (50 %); and grade 3 anemia, n = 3 (50 %). |
| Conclusions: | With this combination, in patients with advanced solid malignancies, sunitinib MTD on Schedule 21 was 37.5 mgday. Sunitinib plus pemetrexed and carboplatin they were tolerable at the MTD, although sunitinib dose delays and reductions they were often required due to myelosuppression. |