| General information |
| Database: | DB00499 |
| Objective: | They conducted a phase I/II trial to determine the safety and efficacy of infliximab in combination with sorafenib in patients with advanced RCC. |
| Authors: | Larkin JM, et al |
| Title: | a phase I/II trial of sorafenib and infliximab in advanced renal cell carcinoma. |
| Journal: | Br J Cancer. |
| Year: | 2010 |
| PMID: | 20842130 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | sorafenib and infliximab
|
| Target: | NA
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | sorafenib+ infliximab |
| Study Type: | a phase I/II trial |
| Key Patients Feature: | histologically proven metastatic RCC;measurable disease according to RECIST 1.0 (Therasse et al, 2000);either systemic treatmentnaive or have progressed after immunotherapy; Eastern Cooperative Oncology Group performance statusof 0 or 1; adequate bone marrow, liver and renal function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Phase I was carried out according to a standard three and three design, respecyively: the first cohort of three patients was treated at fulldose sorafenib 400 mg twice per day (bd) orally and infliximab 5 mg kg 1 intravenously. In the absence of significant safety and toxicity problems in the first cohort, the dose of infliximab was to be escalated to the full dose of 10 mg kg 1 in combination with sorafenib 400 mg bd in the second cohort of three patients. Sorafenib was started on day 0 with standard dose reductions and interruptions for toxicity as necessary. Infliximab was administered at weeks 1, 3 and 7 and then every 4 weeks. |
| Primary End Point: | for phase 1: safety and efficacy: for phase 2: the proportion of patients who were progression free at 6 months (PFS6). |
| Secondary End Point: | toxicity, overall survival and response rate at 12 weeks. |
| Patients Number: | 16 |
| Trial Results |
| DLT_MTD: | Adverse events included grade3 hand-foot syndrome (31%), rash (25%), fatigue (19%) and infection (19%). Although manageable, toxicity resulted in 75% of thepatients requiring at least one dose reduction and 81% requiring at least one dose delay of sorafenib. |
| Objective Response Rate: | Four patients were progression freeat 6 months (PFS6 31%); median PFS and overall survival were 6 and 14 months, respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6 months |
| Median OS A vs. C: | 14 months |
| Adverse Event(agent arm): | Adverse events included grade 3 hand-foot syndrome (31%), rash (25%), fatigue (19%) and infection (19%). Although manageable, toxicity resulted in 75% of the patients requiring at least one dose reduction and 81% requiring at least one dose delay of sorafenib. |
| Conclusions: | Sorafenib and infliximab can be administered in combination, but a significant increase in the numbers of adverse events requiring dose adjustments of sorafenib was observed. There was no evidence of increased efficacy compared with sorafenib alone in advanced RCC. The combination of sorafenib and infliximab does not warrant further evaluation in patients with advanced RCC. |