| General information |
| Database: | DB00704 |
| Objective: | This study aimed to determine the recommendedphase II dose of this targeted combination, their toxicity profile, pharmacokinetic interaction, and preliminary clinical activities. |
| Authors: | Duran I, et al |
| Title: | Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2007 |
| PMID: | 17699864 |
| Trial Design |
| Clinical Trial Id: | NCT00238212 |
| Agent: | sorafenib and erlotinib
|
| Target: | NA
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | sorafenib+erlotinib |
| Study Type: | a dualagent, openlabel, phase I study |
| Key Patients Feature: | patients were required to have a histologicallyconfirmed malignancy, either metastatic or unresectable. Inclusioncriteria included (a) age z18 years; (b) Eastern Cooperative OncologyGroup performance status V2; (c) adequate hematologic, hepatic, andrenal function (absolute neutrophil count z1.5 109/L, plateletsz100 109/L, bilirubin V upper limit of normal, aspartateaminotransferase/alanine aminotransferase V2.5 upper limit ofnormal, and creatinine V upper limit of normal or creatinine clearancez60 mL/min); and (d) 4week interval between study treatment andany prior radiotherapy or chemotherapy. Exclusion criteria included(a) prior treatment with sorafenib, erlotinib, or any agents targetingEGFR, Raf, VEGF, or VEGFR; (b) major surgery within the last 21 days;(c) uncontrolled hypertension (defined as systolic blood pressure>140 mmHg and/or diastolic pressure >90 mmHg in spite of medicaltreatment) or intercurrent illnesses; (d ) bleeding diathesis orcoagulopathy; (e) brain or meningeal metastases; and (f) concurrentuse of enzymeinducing antiepileptic drugs or other CYP3A4 inducers;(Type of tumorNeuroendocrine carcinoma Head and neck squamous cell cancer Hepatocellular cancerSmall cell lung cancer Nasopharyngeal cancer Cholangiocarcinoma )Malignant hemangiopericytoma Ovarian endometrioid cancer Unknown primary adenocarcinoma Thyroid papillary cancer)Bladder transitional cell cancer Anal canal squamous cell cancer Skin squamous cell cancer Duodenum adenocarcinoma) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Sorafenib was administered alone for a 1week runin period, and then both drugs were given together continuously, with every 28 days considered as a cycle. Three dose levels were assessed. |
| Primary End Point: | the recommended phase II dose, their toxicity profile, pharmacokinetic interaction, and preliminary clinical activities |
| Secondary End Point: | NA |
| Patients Number: | 17 |
| Trial Results |
| DLT_MTD: | No DLT was observed at the first dose level. Threepatients were enrolled at dose level 2. Although no DLT wasobserved, hypophosphatemia grade z2 was reported in allpatients prompting a cohort expansion to gain more experiencewith this toxicity. One of four additional patients enrolledpresented with asymptomatic grade 3 hypophosphatemia, resultingin a DLT. |
| Objective Response Rate: | Of the 15 evaluable patients, 3 (20%)achieved a confirmed partial response and 9 (60%) had stabledisease as best response |
| Disease Control Rate: | 0.8 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Fatigue was the most common adverse event (17 patients; 100%) followed by diarrhea (15 patients; 88%), hypophosphatemia (13 patients; 76%), and acneiform rash (12 patients; 71%). These adverse events were predominantly mild to moderate. |
| Conclusions: | Sorafenib and erlotinib are well tolerated and seem to have no pharmacokinetic interactions when administered in combination at their full singleagent recommended doses. This well tolerated combination resulted in promising activity that needs further validation inphase II studies. |