| General information |
| Database: | DB00684 |
| Objective: | Thisphase I study was undertaken to define the toxicity and the maximum tolerated doses (MTD) of the combination in patients with advanced solid tumors. |
| Authors: | Kumar SK, et al |
| Title: | Phase 1 study of sorafenib in combination with bortezomib in patients with advanced malignancies. |
| Journal: | Invest New Drugs. |
| Year: | 2013 |
| PMID: | 23887852 |
| Trial Design |
| Clinical Trial Id: | NCT00303797 |
| Agent: | sorafenib bortezomib
|
| Target: | NA
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | sorafenib + bortezomib |
| Study Type: | Phase I study |
| Key Patients Feature: | Patients over 18 years of age, with cytologic or histologic proof of unresectable cancer without curativetreatment options, were enrolled provided they had adequatehematological (neutrophilsmore than and equal to 1, 500/¦ÌL; hemoglobinmore than and equal to 9 g/dl;plateletsmore than and equal to 100, 000/¦ÌL) and organ function (total bilirubinless than and equal to 1.5x upper limit of normal (ULN), ASTless than and equal to 3¡ÁULN or ASTless than and equal to 5¡ÁULN if liver involvement, creatinineless than and equal to 1.5¡ÁULN). Inclusion onthe study required an ECOG performance status<= 2, noresidual adverse effects from preceding therapy, and no activeinfection. (Tumor siteKidney Lung PancreasBreast Adrenal gland Multiple myeloma CLL Spindle cell tumorMelanoma) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients with cytologic or histologic proof of unresectable solid tumors were treated with escalating doses of sorafenib (twice daily) and bortezomib (days 1, 4, 8 and 11 intravenously) with 21day cycles. |
| Primary End Point: | MTD, DLTs, tumor response and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 14 |
| Trial Results |
| DLT_MTD: | The recommendedphase 2 doses are sorafenib 200 mg twice daily continuously with bortezomib 1 mg/m(2) on days 1, 4, 8, 11 (21 day cycles); DLT was seen in two patients (one grade 3 abdominal pain and grade 4 lipase elevation; one with grade 3 vomiting) |
| Objective Response Rate: | One patient with renal cell cancer had a partial response and 5 patients attained stable disease. |
| Disease Control Rate: | NA |
| Median Time to Progression: | The median time to progression for the entire cohort was 53 days: 48 days in dose level 1 and 90 days in dose level 2. |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | no grade 4 hematologic toxicities or grade 5 toxicities were seen in this study. One grade 4 fatigue and one grade 4 lipase (one of the reported DLTs) were observed during cycle 1. The most common cycle 1 toxicities reported included gastrointestinal toxicities (nausea, anorexia), dermatologic (rash, pruritus), fatigue, and hematological (thrombocytopenia) toxicities. |
| Conclusions: | The combination of sorafenib and bortezomib was tolerated well. The recommendedphase 2 doses are sorafenib 200 mg twice daily continuously with bortezomib 1 mg/m(2) on days 1, 4, 8, 11 (21 day cycles). The combination shows preliminary signs of efficacy, supportingphase 2 studies. |