| General information |
| Database: | DB00344 |
| Objective: | Phase I study to determine the maximum tolerated dose (MTD) of fluorouracil (FU) in the docetaxel/cisplatin/FU (TPF) regimen when combined with cetuximab (C) for induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). |
| Authors: | Haddad RI, et al |
| Title: | Phase I study of CTPF in patients with locally advanced squamous cell carcinoma of the head and neck. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19704061 |
| Trial Design |
| Clinical Trial Id: | NCT00402545 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced Squamous cell carcinoma of the head and neck |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | docetaxel/cisplatin/FU (TPF) regimen when combined with cetuximab (C) for induction treatment |
| Study Type: | Phase I study |
| Key Patients Feature: | Patients with stage III or IV, previously untreated, locally advancedSCCHN were eligible for participation in thisphase I study. Primary sitesallowed included the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, and unknown primary. Additional eligibility criteria included measurabledisease based on Response Evaluation Criteria in Solid Tumors guidelines, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal hematologic, renal, and liver function |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | FU cohorts were 700, 850, and 1, 000 mg/m(2)/d for 4 days via continuous infusion. TPF given every 3 weeks for three cycles and C was given weekly for a total of 9 weeks, starting on day 1 of TPF. All patients received chemoradiotherapy after CTPF. |
| Primary End Point: | the maximumtolerated dose (MTD) |
| Secondary End Point: | toxicity of the combination and the response rate of the combined CTPF regimen |
| Patients Number: | 30 |
| Trial Results |
| DLT_MTD: | No doselimiting toxicity (DLT) was encountered on dose levels 1 and 2. At dose level 3 of 1000mg/m2, one DLT was encountered and three more patients were enrolled with no DLTs. In the expansion cohort at the MTD, three DLT¡¯s were encountered. The decision was made to decreasethe FU from 1, 000 mg/m2 to dose level 2 of 850 mg/m2. |
| Objective Response Rate: | clinical response, six partial responses and 22 complete responses for an overall response rate of 100%. Perradiographic criteria, all patients attained a partial response |
| 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 major reasons to hold cetuximab were: skin rash, mostlyacneiform rash affecting the face, which occurred in eight patients; paronychial changes (fissure, infection) occurring in eight patients; and patients with a DLT. |
| Conclusions: | CTPF appears to be safe and feasible as given in this study. GI toxicity (mucositis, enteritis, and diarrhea) appears to be the major combined DLT. Reducing the FU in TPF to 850 mg/m(2) reduces GI toxicity and is the recommendedphase II dose. |