| General information |
| Database: | DB00251 |
| Objective: | To determine the maximal tolerated dose (MTD) of the combination of weekly temsirolimus and every other week vinorelbine in patients with advanced or refractory solid tumors. |
| Authors: | Piatek CI, et al |
| Title: | Phase I clinical trial of temsirolimus and vinorelbine in advanced solid tumors. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2014 |
| PMID: | 25374407 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | temsirolimus+ vinorelbine |
| Study Type: | an openlabel, single center, nonrandomized, doseescalatingphase I study |
| Key Patients Feature: | patients with advanced or refractory solid tumors;tumor types included lung (5), prostate (2), neuroendocrine of pancreas (1), bladder (2), uterus (3), cervix (4), and vagina (2). |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with intravenous temsirolimus on days 1, 8, 15, and 22 and intravenous vinorelbine on days 1 and 15. Cycles were repeated every 28 days. |
| Primary End Point: | MTD, DLT, ORR, toxicity |
| Secondary End Point: | NA |
| Patients Number: | 19 |
| Trial Results |
| DLT_MTD: | There was 1 doselimiting toxicity at level II (grade 3 anorexia/dehydration) and 2 at level III (grade 3 hypokalemia; grade 4 neutropenia). Two patients died at dose level III; one was studyrelated with grade 4 neutropenia. Temsirolimus 25 mg given days 1, 8, 15, and 22 in combination with vinorelbine 20 mg/m(2) given days 1 and 15 every 4 weeks was found to be the MTD. |
| Objective Response Rate: | Best response included two patients (prostate and non small cell lung cancer) with partial response. |
| Disease Control Rate: | eight patients with stable disease |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 3/4 toxicities observed during the first cycle included neutropenia (2), anemia (1), anorexia (1), dehydration (1), hyperglycemia (1), hypertriglyceridemia (1), and hypokalemia (1). |
| Conclusions: | Temsirolimus 25 mg given days 1, 8, 15, and 22 in combination with vinorelbine 20 mg/m(2) given days 1 and 15 every 4 weeks was found to be the MTD. This dose combination is considered feasible inphase II trials. |