| General information |
| Database: | DB00380 |
| Objective: | They conducted a phase I study to assess the safety, tolerance, maximal tolerance dose (MTD) and efficacy of hR3 in combination with concurrent chemoradiation in patient with locally advanced esophageal carcinoma. |
| Authors: | Zhao KL, et al |
| Title: | a phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus. |
| Journal: | Invest New Drugs. |
| Year: | 2012 |
| PMID: | 21901403 |
| Trial Design |
| Clinical Trial Id: | NCT00950417 |
| Agent: | nimotuzumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer |
| Cancer Subtype: | stage IIIVa esophageal carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Nimotuzumab + concurrent chemoradiation |
| Study Type: | phase I dose escalation study |
| Key Patients Feature: | (1)cytologically or histologically confirmed esophageal carcinoma; (2) age of 18-75; (3)locally advanced, stage IIIVa (AJCC, 2002); (4)performance status of ECOG 0-2; (5) no treatments prior toenrollment; (6) at least one measurable lesion on CT, MRIor esophageal barium exam; (7) normal functions of heart, lung, liver, kidney and bone marrow; (8) blood examsqualified for chemotherapy, which included hemoglobulinof more than and equal to 9 g/dl, neutrophil more than and equal to 1.5¡Á109/L and platelet (PLT) more than and equal to 100¡Á109/L, creatinine less than and equal to 1.5 UNL; and (9) informed consentsigned. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | A total dose of 61.2 Gy was delivered by conventional fractionation. Chemotherapy was concurrently administered with irradiation every 4 weeks with PF regimen (cisplatinum of 25 mg/m(2)/d, d13; 5Fu of 1, 800 mg/m(2), intravenously infusion in 72 h) for 4 cycles. hR3 was administrated weekly during irradiation for 6 weeks. hR3 dose escalation started with 100 mg/week, and followed by 200 mg/week and 400 mg/week. Three patients were enrolled in of each dose cohort. 11 patients were enrolled in the trial with 3, 4 and 4 in 100 mg/week, 200 mg/week and 400 mg/week cohort, respectively. 2 patients in 200 mg/week and 400 mg/week cohort were withdrawn due to patients' own decisions. |
| Primary End Point: | DLTs, MTD, PFS, OS |
| Secondary End Point: | NA |
| Patients Number: | 14 |
| Trial Results |
| DLT_MTD: | No dose limiting toxicity was observed. Grade 3-4 of esophagitis, Grade 3 of leucocytopenia and neutrocytopenia occurred in 18% (2/11), 18%(2/11) and 9% (1/11) of patients, respectively MTD has not been reached yet |
| Objective Response Rate: | For local response rate in nine patients, who completed theplanned treatment, two patients (22%) reached completeresponse (CR), 5 (56%), partial response (PR), and 2(22%), stable disease (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): | No dose limiting toxicity was observed. Grade 3-4 of esophagitis, Grade 3 of leucocytopenia and neutrocytopenia occurred in 18% (2/11), 18% (2/11) and 9% (1/11) of patients, respectively.For nimotuzumabrelated toxicity only one patient experienced Grade 1 skin rash, and no Grade more than and equal to 3 of toxicity was noticed. In 9 patients, who completed planned treatments, 6month and 1year overall survival were 78% and 67%, respectively, and 1 year local progression free survival, 100%. hR3 of 400 mg/week administered concurrently with chemoradiation was welltolerant. MTD has not been reached yet. |
| Conclusions: | For nimotuzumabrelated toxicity only one patient experienced Grade 1 skin rash, and no Grade more than and equal to 3 of toxicity was noticed. In 9 patients, who completed planned treatments, 6month and 1year overall survival they were 78% and 67%, respectively, and 1 year local progression free survival, 100%. hR3 of 400 mgweek administered concurrently with chemoradiation was welltolerant. MTD has not been reached yet. |