| General information |
| Database: | DB00920 |
| Objective: | Thisphase I study evaluated the safety, tolerability, maximum tolerated dose (MTD), and recommendedphase II dose (RP2D) of tivantinib combined with sorafenib in patients with advanced solid tumors. |
| Authors: | Puzanov I, et al |
| Title: | Phase 1 trial of tivantinib in combination with sorafenib in adult patients with advanced solid tumors. |
| Journal: | Invest New Drugs. |
| Year: | 2015 |
| PMID: | 25294187 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | tivantinib sorafenib
|
| Target: | NA
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | tivantinib + sorafenib |
| Study Type: | Phase I trial |
| Key Patients Feature: | patients were enrolled if they met the following criteria: were 18 years of age or older; had advanced or metastatic solid tumors for which no effective treatment was available |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | A standard 3 + 3 dose escalation design was used. At the RP2D, expansion cohorts in 5 tumor types could be enrolled. Pharmacogenetic and pharmacodynamic analysis were performed. |
| Primary End Point: | safety, tolerability, maximum tolerated dose (MTD), and recommendedphase II dose (RP2D |
| Secondary End Point: | NA |
| Patients Number: | 87 |
| Trial Results |
| DLT_MTD: | The ecommendedphase II dose (RP2D) was tivantinib 360 mg BID and sorafenib 400 mg BID for all cancer histologies, except in hepatocellular carcinoma (hepatocellular carcinoma) patients tivantinib was 240 mg BID plus sorafenib 400 mg BID. |
| Objective Response Rate: | in all patients was 11.5 % with the highest ORR observed in melanoma (26.3 %), followed by RCC (15.0 %) and hepatocellular carcinoma (10.0 %). |
| Disease Control Rate: | 58 % in all patients, 90 % in RCC, 65 % in hepatocellular carcinoma, 63 % in melanoma, 40 % in breast cancer, and 8 % in non small cell lung cancer patients. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.6 months (95 % CI: 3.4-5.3 months) in all patients with the longest PFS observed in RCC patients (7.2 months, 95 % CI: 4.8-12.9 months), following by melanoma (4.9 months, 95 % CI: 1.7-5.6 months) and hepatocellular carcinoma (3.5 months, 95 % CI: 3.0-11.1 months) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | he most common treatmentrelated adverse events (AE) were rash (40 %), diarrhea (38 %), and anorexia (33 %). |
| Conclusions: | The combination treatment could be administered at full standard singleagent doses in all patients except those with hepatocellular carcinoma, where tivantinib was lothey wered to 240 mg BID. Preliminary evidence of anticancer activity was observed in patients with RCC, hepatocellular carcinoma, and melanoma, including patients refractory to sorafenib andor other antiVEGF pathway therapies. The combination treatment has therapeutic potential in treating a variety of solid tumors. |