| General information |
| Database: | DB00671 |
| Objective: | Improvements in knowledge of molecular mechanisms in cancer are the basis for new studies combining chemotherapy with targeted drugs. Inhibition of the epidermal growth factor receptor (EGFR) by erlotinib or cetuximab has limited or no activity, respectively, in pancreatic cancer. The crosstalk between EGFR and mammalian target of rapamycin (mTOR) pathways is a potential mechanism of resistance; therefore they conducted a study to explore safety and efficacy of multiple pathway inhibition by cetuximab and everolimus in combination with capecitabine. |
| Authors: | Kordes S, et al |
| Title: | a phase I/II, nonrandomized, feasibility/safety and efficacy study of the combination of everolimus, cetuximab and capecitabine in patients with advanced pancreatic cancer. |
| Journal: | Invest New Drugs. |
| Year: | 2013 |
| PMID: | 22367239 |
| Trial Design |
| Clinical Trial Id: | NCT01077986 |
| Agent: | everolimus, cetuximab
|
| Target: | NA
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | advanced pancreatic cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | everolimus, cetuximab + capecitabine |
| Study Type: | multicenter openlabelphase I/II trial |
| Key Patients Feature: | Patients with cytological or histological confirmed locally advanced or metastatic adenocarcinoma of the pancreas were eligible. Further inclusion criteria comprisedan Eastern cooperative oncology group/World healthorganization (ECOG/WHO) performance status of 0, 1or 2, measurable lesions on CT according to RECIST1.0 criteria (for the phase II part of the study), ageeighteen years of age or older and a lifeexpectancy ofat least three months. Patients had to be mentally, physically and geographically able to undergo treatment andfollowup. Adequate renal, liver and bone marrow function was necessary. Laboratory values accompaniedhereby were serum creatinine <150 ¦Ìmol/L, bilirubin<1.5x upper limit of laboratory normal (ULN), aspartateaminotransferase and alanine aminotransferase <2.5xULN or <5.0x in case of liver metastasis, white bloodcell count >3.0x109, platelets >100x109, respectively. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Safety and efficacy of fixed standard dose cetuximab in combination with various dose levels of everolimus (510 mg/day) and capecitabine (600800 mg/m(2) bid, 2 weeks every 3 weeks) were investigated. |
| Primary End Point: | objective response. |
| Secondary End Point: | NA |
| Patients Number: | 16 |
| Trial Results |
| DLT_MTD: | Mucositis, rash and handfoot syndrome were doselimiting toxicities. Dose level 1 (everolimus 5 mg/day, capecitabine 600 mg/m(2) bid for 2 weeks every 3 weeks and cetuximab 250 mg/m(2) weekly) was considered the maximum tolerated dose (MTD). |
| Objective Response Rate: | Of 31 patients in the phase II part, partial response was documented in two patients (6.5%) and five (16.1%) had stable disease. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 5.0 months (CI 3.1-6.8) |
| Adverse Event(agent arm): | Mucositis, rash and handfoot syndrome were doselimiting toxicities. |
| Conclusions: | The schedule of capecitabine, everolimus and cetuximab resulted in considerable epidermal and mucosal toxicities and prevented escalation to optimal dose levels. Because of toxicity and low efficacy this treatment combination cannot be recommended for treatment in pancreatic cancer patients. |