| General information |
| Database: | DB00336 |
| Objective: | Thisphase I study was designed to investigate the safety and tolerability of combining weekly cisplatin treatment with cetuximab and hyperfractionatedaccelerated radiotherapy (HART) for locally advanced SCCHN. |
| Authors: | Kuhnt T, et al |
| Title: | Phase I trial of doseescalated cisplatin with concomitant cetuximab and hyperfractionatedaccelerated radiotherapy in locally advanced squamous cell carcinoma of the head and neck. |
| Journal: | Ann Oncol. |
| Year: | 2010 |
| PMID: | 20427347 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | cisplatin with concomitant cetuximab and hyperfractionatedaccelerated radiotherapy |
| Study Type: | Phase I trial |
| Key Patients Feature: | Patients aged 18 and 70 years were eligible for inclusion if they had beendiagnosed with histologically confirmed unresectable squamous cellcarcinoma of the oral cavity (excluding the lip), oropharynx, hypopharynxor larynx measurable in one dimension and classified as stage III or IVA/B(International Union Against Cancer). In the phase I protocol no humanpapillomavirus status or p16 was determined in oropharynx carcinoma.Furthermore, inclusion required a Karnofsky Index (KI) 70% andadequate pulmonary, cardiac, bone marrow, hepatic and renal functions.Study treatment was given in curative intent. Before the initiation ofradiotherapy, all patients had to undergo a dental examination and receiveda percutaneous endoscopic gastrostomy. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with cetuximab, 400 mg/m2 initial dose on day 7 of HART, followed by 250 mg/m2 weekly during the administration of HART, which started with 2.0 Gy/day (5 days/week) for 3 weeks followed by 1.4 Gy/twicedaily (Monday to Friday) for another 3 weeks, resulting in a total dose of 70.6 Gy. Cisplatin was administered weekly starting on the first day of radiotherapy until week 6. Cisplatin was dose escalated of four dose levels from 20 to 40 mg/m2 using a classical 3 + 3 dose escalation algorithm. |
| Primary End Point: | the MTD of cisplatin in combination with cetuximab and HART, according to the incidence of doselimiting toxic effects (DLTs). |
| Secondary End Point: | acute toxicity and objective tumor response rate (ORR). |
| Patients Number: | 18 |
| Trial Results |
| DLT_MTD: | No maximum tolerated dose was reached for cisplatin. One of six patients of dose level 4 had grade 4 neutropenia. The most common types of grade 3+ adverse events weremucositis (9 of 16 patients), infield dermatitis (6 of 16 patients) and neutropenia (4 of 16 patients). |
| Objective Response Rate: | 5 complete responses, 8 partial responses and 1 progressive disease (at distant sites) were documented in a total of 15 patients(objective response rate 87%). |
| Disease Control Rate: | 0.87 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2 years PFS: 9/15 (60%) |
| Median OS A vs. C: | 2 years OS: 12/15 (80%) |
| Adverse Event(agent arm): | Sixteen patients were eligible for toxicity, and 15 for response. No maximum tolerated dose was reached for cisplatin. One of six patients of dose level 4 had grade 4 neutropenia. This patient died 1 week after the end of the study treatment. The most common types of grade 3+ adverse events were mucositis (9 of 16 patients), infield dermatitis (6 of 16 patients) and neutropenia (4 of 16 patients). Cetuximabrelated hypersensitivity was observed in 1 out of 18 patients. |
| Conclusions: | The combination of cisplatin with cetuximab and HART is active, well tolerated and merits additional investigation. The recommended weekly dose of cisplatin forphase II studies is 40 mgm2. |