Treatment Selection According to Skin Reaction to Cetuximab
The therapy of patients with locally advanced head and neck cancer will be adjusted to the grade of skin rush as recorded after the first two cycles of Cetuximab and Cisplatin, i.e. either with radioimmunotherapy (radiotherapy and Cetuximab) or radiochemotherapy (radiotherapy and Cisplatin.
Head and Neck Cancer
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Skin Reaction to Cetuximab as Criteria for Treatment Selection in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Phase 2 Study|
- locoregional complete response rate [ Time Frame: 12-14 weeks after therapy ] [ Designated as safety issue: No ]The primary objective of the study is to determine radiologically the complete response rate 12-14 weeks after therapy.
- feasibility (toxicity profile) of the proposed regimen [ Time Frame: participants will be followed for the duration of treatment (an expected average of 20 weeks) ] [ Designated as safety issue: Yes ]number of patients with adverse events graded according to the National Cancer Institute CTC v3.0 (as measure of safety and tolerability)
- locoregional control [ Time Frame: at 2 years after thapy ] [ Designated as safety issue: No ]Locoregional control will be calculated from the first day of the therapy to the occurrence of the local and/or regional recurrence (whichever will occur first) or death from any cause other than distant metastasis.
- progression-free survival [ Time Frame: 2 years after therapy ] [ Designated as safety issue: No ]Progression-free will be calculated from the first day of the therapy to the appearance of local or regional recurrence, distant metastases, secondary primary cancer or death from any cause.
- overall survival [ Time Frame: 2 years after therapy ] [ Designated as safety issue: No ]Overall survival is defined as a time interval between the first day of therapy and death from any cause.
- late toxicity including thyroid function [ Time Frame: up to 2 years post-therapy ] [ Designated as safety issue: Yes ]number of patients with adverse events graded according to the National Cancer Institute CTC v3.0 (as measure of safety and tolerability)
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Background: According to literature, the treatment results in irradiated patients who develop intensive skin reaction after concomitant Cetuximab administration appear improved as compared to the results of standard combination of radiotherapy and Cisplatin. In other patients, no beneficial effect of Cetuximab is expected and the therapy with Cisplatin (concomitantly with irradiation) is more effective in this group.
In this proposed single-institution non-randomized phase II study on patients with locally advanced squamous cell carcinoma of the head and neck, the therapy will be adjusted to the grade of skin rush as recorded after the first two cycles of Cetuximab and Cisplatin, i.e. either with radioimmunotherapy (radiotherapy and Cetuximab) or radiochemotherapy (radiotherapy and Cisplatin).
Methods: In the patients with inoperable tumors, induction chemotherapy (Docetaxel 75 mg/m2, Cisplatin 75 mg/m2, 5-Fluorouracil 750 mg/m2 in continuous infusion days 1-5; repeated every 21 days for 4 cycles) will be administered. In the week before the first fraction of radiotherapy, all patients will receive a loading dose of Cetuximab (400 mg/m2) and combination of Cetuximab (250 mg/m2) and Cisplatin (30 mg/m2) during the first week of irradiation. After multidisciplinary assessment of the grade of skin rush, conducted at the end of the second week of irradiation, the patients will be grouped as follows: arm A - skin rush of CTCAE v3.0 grade <2 will proceed with radiochemotherapy with Cisplatin; arm B - skin rush of CTCAE v3.0 grade >=2 will proceed with radioimmunotherapy with Cetuximab.
The planned number of patients included in the study is 120 (arm A - 50, arm B - 70) and recruitment period is 3 years. The primary objective of the study is to determine radiologically the complete response rate 12-14 weeks after therapy. The secondary objectives are locoregional control, progression-free survival and overall survival at 2 years after therapy, acute and late toxicity.
Expected results: The expected complete response rate in patients treated with radiochemotherapy and those treated with radioimmunotherapy is 50% and 75%, respectively. We also expect the difference in an absolute survival gain between the groups to be 25%.
|Contact: Primož Strojan, Prof.||firstname.lastname@example.org|
|Institute of Oncology Ljubljana||Recruiting|
|Ljubljana, Slovenia, SI-1000|
|Contact: Primož Strojan, Prof. email@example.com|
|Sub-Investigator: Marta Dremelj, MD, MSc|
|Sub-Investigator: Igor Fajdiga, MD, PhD|
|Sub-Investigator: Cvetka Kuhar Grašič, MD, PhD|
|Sub-Investigator: Jančar Boris, MD, MSc|
|Sub-Investigator: Simona Jereb, MD|
|Sub-Investigator: Katarina Karner, MD, MSc|
|Sub-Investigator: Barbara Žumer, MD|
|Principal Investigator:||Primož Strojan, Prof.||Dept. of Radiation Oncology, Institute of Oncology Ljubljana, Slovenia|
|Principal Investigator:||Branko Zakotnik, Prof.||Dept. of Medical Oncology, Institute of Oncology Ljubljana, Slovenia|