Trial of Induction Chemotherapy (ICT) Followed by Concurrent Chemoraditherapy (CR) With Monoclonal Antibody Cetuximab in Locally Advanced Head and Neck Squamous Cell Cancer
This is an open label, single arm Phase II study of induction chemotherapy followed by concurrent chemo-radiotherapy in patients with locally advanced head and neck squamous cell cancer (HNSCC) using monoclonal antibody cetuximab. Those patients with locally advanced HNSCC deemed to be candidates for definitive concurrent chemo-radiotherapy will be treated initially with 6 weeks of PCC (Paclitaxel, cetuximab and Carboplatin). This will be followed by a week of no treatment for interim evaluation, followed by definitive concurrent chemo-radiotherapy using 70Gy radiation with weekly cetuximab and cisplatin for 7 weeks. The hypothesis of the study is that the use of cetuximab during induction chemotherapy followed by cetuximab concurrent with chemoradiotherapy using low dose weekly cisplatin will improve local control as well as distant spread.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Induction Chemotherapy (ICT) Followed by Concurrent Chemoraditherapy (CR) With Monoclonal Antibody Cetuximab in Locally Advanced Head and Nec Squamous Cell Cancer|
- Complete Response [ Time Frame: Analysis at Week 26 ] [ Designated as safety issue: No ]Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
- Progression Free Survival [ Time Frame: Same as Primary Outcome Measure ] [ Designated as safety issue: No ]Improvement in progression free survival (PFS)in locally advanced stage III and IV head and neck cancer patients with sequential (ICT) followed by Concurrent chemo-radiotherapy (CR) using monoclonal antibody Cetuximab as compared to historical controls.
|Study Start Date:||June 2010|
|Study Completion Date:||February 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Single arm phase II study
Single arm phase II study of chemotherapy
Other Name: Single arm phase II study
Chemotherapy would be used in two phases. In the initial phase all patients would be treated with ICT involving 6 cycles of PCC. This involves Cetuximab 400mg/m2 Week 1 and then 250mg/m2 weekly, Paclitaxel 80mg/m2 weekly and carboplatin AUC 2 weekly for 6 weeks followed by concurrent chemoradiotherapy with cetuximab. After ICT patients would be given weekly Cisplatin at 30mg/m2 and cetuximab at 250mg/m2 concurrent with radiation therapy.
Typically for tumors treated by megavoltage (6MV) radiotherapy alone or with chemotherapy, the primary tumor bed with an adequate margin and the draining lymphatics will be treated with parallel opposed lateral treatment portals; the lower neck node bearing area will be treated through an anterior port. The standard total dose for the targeted tumor bed and electively treated lymphatics is 50 Gy/25 fractions, and then, an additional boost dose to the neoplasm-bearing site(s) of 16 Gy to 20 Gy.
The total dose received by the spinal cord should not be allowed to exceed 46 Gy. For N1 to N3 disease, they also shall need a total dose (boost included) of 66 Gy and perhaps up to 70 Gy if it can be safely given 6.4 Study Outline:
- Patients who are deemed eligible and sign informed consent would be enrolled in the clinical trial.
- Prior to starting therapy staging PET/CT scan, medical history, physical exam, hematologic and biochemical testing will be undertaken.
- Since mucositis and oropharyngeal dysfunction is very likely with chemo-radiation PEG tube placements will be considered prior to treatment, in order to allow adequate nutrition in case of mucositis.
- Prior to starting radiation patients would undergo dental evaluation which is a standard practice.
- Patients would then undergo 6 weeks of ICT using PCC. Based on toxicity dose would be modified as described in section 8.
- For PCC regimen, cetuxmiab would be given first followed by paclitaxel and then carboplatin using standard pre-medication.
- A CT scan (no PET scan) of the head and neck will be performed during the evaluation Week 7 on any day of that week.
- Following induction chemotherapy patients would be treated with radiation therapy of up to 70 Gy concurrent with weekly Cisplatin at 30mg/m2 and cetuximab at 250mg/m2 for the duration of radiation therapy. Again dose modifications would be performed based as described in section 8.
- Cetuximab would be administered first followed by cisplatin concurrent with radiation.
- History and Physical examination would be performed at the end of treatment to document response and assess toxicity
10. Patient with residual disease at the primary site or neck after completion of chemoradiotherapy would be offered surgery.
11. Week 26 (3 months) after completion of radiation therapy a repeat PET scan will be performed to assess response which is standard of care.
12. After completion of all treatment patients will be followed at every 3 months interval to document relapse or manage toxicities from treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01326923
|United States, Louisiana|
|LSU Health Sciences Center|
|Shreveport, Louisiana, United States, 71103|
|Principal Investigator:||Syed H Jafri, MB,B,S||LSU shreveport|