| General information |
| Database: | DB00731 |
| Objective: | This trial of patients with metastatic CRC (MCRC) examined the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of erlotinib in combination with capecitabine and oxaliplatin (XELOX), a regimen with established efficacy. |
| Authors: | Van Cutsem E, et al |
| Title: | a phase Ib doseescalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients. |
| Journal: | Ann Oncol. |
| Year: | 2008 |
| PMID: | 17986625 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | erlotinib, capecitabine and oxaliplatin |
| Study Type: | a phase Ib doseescalation study |
| Key Patients Feature: | Patients with histologically confirmed MCRC, at least one measurablelesion according to the response evaluation criteria in solid tumors(RECIST) [30], Eastern Cooperative Oncology Group performance statuszero to one, 18 years of age and a life expectancy 12 weeks were eligiblefor the trial. Patients could be chemotherapy naive or had one previoustreatment with 5FU and/or irinotecan for MCRC. Exclusion criteriaincluded: prior chemotherapy/radiotherapy <4 weeks before trial entry (oradjuvant chemotherapy <6 months before), hypersensitivity tofluoropyrimidines, peripheral neuropathy with functional impairment, inadequate renal, hepatic, cardiopulmonary or hematologic function |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients previously untreated or treated with one line of 5fluorouracil and/or irinotecan received escalating oral doses of erlotinib (daily), capecitabine (days 114) and i.v. oxaliplatin (day 1 of a 21day cycle). |
| Primary End Point: | maximum tolerated dose (MTD) of the triplet combination, and safety |
| Secondary End Point: | pharmacokinetics (PK) and preliminary antitumor efficacy |
| Patients Number: | 23 |
| Trial Results |
| DLT_MTD: | The MTD for this combination in MCRC is capecitabine 825 mg/m2 twice daily days 1-14, oxaliplatin130 mg/m2 day 1 and erlotinib 100 mg/day of a 21day cycle. |
| Objective Response Rate: | The majorityof patients had stable disease Standard deviation, (SD)(duration 7 weeks to >47 weeks), a PR (duration 9 weeks to >53weeks) or a CR. Five secondline patients were assessable for response, two in cohort 1 (one PR, one SD) and three in cohort2 (one PR, two SD) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events (AEs) were diarrhea and rash. There was a trend for reduced capecitabine concentrations in the presence of erlotinib. One patient died, due to multiorgan failure, which was not considered treatment related. Two patients in cohort 1 withdrew due to AEs; one with HenochSchonlein purpura (possibly treatment related), and one with dysesthesia (probably treatment related) and obstruction (unrelated). In cohort 2, two patients withdrew due to AEs; one due to diarrhea (probably treatment related) and one due to intestinal ischemia (unrelated). |
| Conclusions: | The MTD for this combination in MCRC is capecitabine 825 mg/m(2) twice daily days 114, oxaliplatin 130 mg/m(2) day 1 and erlotinib 100 mgday of a 21day cycle. The combination was well tolerated at the MTD, with no unexpected AEs. The use of this combination in MCRC warrants further investigation. |