| General information |
| Database: | DB00312 |
| Objective: | The purpose of thisphase IB trial was to evaluate the tolerability, pharmacokinetics and preliminary evidence of antitumor activity of erlotinib plus gemcitabine in patients with pancreatic cancer and other solid tumors. |
| Authors: | Dragovich T, et al |
| Title: | Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors:phase IB trial. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2007 |
| PMID: | 17149608 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Erlotinib+gemcitabine |
| Study Type: | phase IB trial |
| Key Patients Feature: | male and femalepatients, aged 18 years, documented diagnosisof locally advanced or metastatic pancreatic adenocarcinoma or another epithelial malignancy, gemcitabinena ve, no restriction on prior number of other chemotherapyregimens, performance status 70% by Karnofskyscale, absolute neutrophil count 1, 500/mm3, plateletcount 100, 000/mm3, bilirubin .2 mg/dl, aspartateaminotransferase (AST) and alanine aminotransferase(ALT) .2 times the upper limit of normal (ULN) forthe institution (5 times if due to hepatic metastases), serum albumin 2.5 g/dl, creatinine .1.5 times theULN or creatinine clearance 60 ml/min |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | In the escalatingphase of the trial, patients were enrolled in sequential cohorts using 100 or 150 mg oral daily dosing of erlotinib. Gemcitabine dose was 1, 000 mg/m(2) weekly x 7 (first cycle), then weekly x 3, every 4 weeks. |
| Primary End Point: | the safety, tolerability, pharmacokinetic interactions and maximally tolerated dose. |
| Secondary End Point: | the preliminary antineoplastic activity , as measured by objective response rate, progression free survival and estimated median survival. |
| Patients Number: | 26 |
| Trial Results |
| DLT_MTD: | In Cohort IA, at the 100 mg/day doseof erlotinib, three patients have developed grade 3 transaminase elevations. After stricter inclusion criteriawere adopted (Cohort IB), no additional events ofgrade 3 transaminase elevations were observed and thedose of erlotinib was escalated to 150 mg/day (CohortsIB and IIB) without reaching doselimiting toxicities |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Patients with unresectable or metastatic pancreatic cancer (n = 15) had a median progression free survival of 289 days |
| Median OS A vs. C: | 389 days (12.5 months), and a 1year survival rate of 51%. |
| Adverse Event(agent arm): | The most common toxicities included diarrhea, skin rash, fatigue and neutropenia. |
| Conclusions: | The 150 mgday dose of erlotinib can be safely administered in combination with standard dose gemcitabine in selected patients with pancreatic cancer and other advanced solid tumors. Promising antitumor activity has been observed in patients with pancreatic cancer. |