Pilot Study for Locally Advanced Head and Neck Cancer
Induction chemotherapy is gaining momentum in the management of locally advanced squamous cell carcinoma of the head and neck (SCCHN). The combination of docetaxel, cisplatin, and 5-FU (TPF) was superior compared with PF in a Phase III clinical trials73,74. We have completed a Phase II clinical trial that showed that docetaxel, cisplatin, and cetuximab (TPE) is highly active and well tolerated as induction chemotherapy in SCCHN (Argiris et al. ASCO 2008; A6002). Preliminary survival results are very encouraging. 39 patients were enrolled and with median follow up 26 months the 2-year PFS was 70% and the 2-year OS 84%.The combination of chemotherapy plus cetuximab is already a standard treatment in recurrent or metastatic SCCHN47. Therefore, TPE can be used as the platform for the addition of novel agents.
EGFR and VEGF are among the most important and validated molecular targets in cancer therapy. The incorporation of novel targeted therapies to chemotherapy and radiotherapy is of particular interest in head and neck cancer, and may improve efficacy without significantly increasing toxicity. A Phase III trial of carboplatin/paclitaxel/bevacizumab with or without cetuximab in advanced NSCLC has been proposed by SWOG. Bevacizumab is currently being investigated in SCCHN with promising results. A Phase II study investigating the combination of pemetrexed and bevacizumab (UPCI 05-002) as well as a Phase II trial of cetuximab and bevacizumab (UPCI 05-087) in recurrent or metastatic SCCHN are ongoing at the University of Pittsburgh with encouraging results (ASCO 2008 and ASCO 2009). In this study, 32 have been already enrolled. There was only 1 patient with grade 3 hemorrhage. The objective response rate is 20%, the median PFS 2.8 months and the median OS 8.1 months.
In order to further improve the efficacy of TPE and the rate of complete responses we propose to add bevacizumab to the TPE followed by XPE regimen we developed at the University of Pittsburgh. Due to non-overlapping toxicities and based on our prior experience we anticipate that the regimen will be well tolerated. Moreover, we plan to obtain tumor biopsies and blood samples in the first cycle and evaluate the modulation of biomarkers post combination therapy. Data from induction with TPE (presented at ASCO 2009) indicate the potential significance of cytokine levels in patient outcome. Also, we will evaluate the feasibility of subsequent concurrent radiation, cisplatin, cetuximab and bevacizumab. Patients with stable disease in the primary could be considered candidates to surgical resection at the discretion of their physician, if the tumor is resectable.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of Induction Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A) in Patients With Locally Advanced Head and Neck Cancer|
- Response rate [ Time Frame: 10 years ] [ Designated as safety issue: No ]To evaluate the rate of complete responses with induction with cisplatin, docetaxel, cetuximab and bevacizumab (TPE-A) in patients with locally advanced head and neck cancer.
- Serum Correlatives [ Time Frame: 10 years ] [ Designated as safety issue: No ]To evaluate serum cytokines and to correlate with complete response rate post induction therapy.
- Biomarkers [ Time Frame: 10 years ] [ Designated as safety issue: No ]To collect tumor tissue from pretreatment and post-treament (optional) biopsies for biomarker studies on tumor tissue. We plan to investigate a panel of EGFR and angiogenesis biomarkers on Tissue Microarrays (TMAs).
- Toxicity [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]To evaluate the toxicities associated with induction TPE-A and subsequent concurrent radiation, cispaltin, cetuximab and bevacizumab (XPE-A).
- Response rate and progression-free survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]To evaluate the objective response rate post XPE-A, and the progression- free survival and overall survival and quality of life.
|Study Start Date:||December 2010|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
Experimental: Study Intervention
Induction therapy consists of 3 cycles of bevacizumab 15mg/kg on day 1, cetuximab weekly days 1,8,15 (loading dose of cetuximab 400mg/m2 on cycle 1, day 1, then 250 mg/m2 on all subsequent administrations), cisplatin 75mg/m2 on day 1, docetaxel 75mg/m2 on day 1, repeated every 21 days. After 3 cycles of induction therapy, patients will receive standard radiation 70-74 Gy/ 200 cGy/ daily, 5 days/ week with concurrent weekly cisplatin 30mg/m2, cetuximab 250mg/m2 and bevacizumab 15mg/kg every 3 weeks x 3. There is optional surgery for non-responders in the primary (stable disease) after TPE-A.
Bevacizumab, 15 mg/kg IV over 30 minutes (if this infusion rate was well tolerated), every 3 weeks until completion of radiation The initial dose will be delivered over 90+/-15 minutes. If the first infusion is tolerated without infusion associated adverse events (fever and/or chills), the second infusion may be delivered over 60+/-10 minutes. If the 60 minute infusion is well tolerated, all subsequent infusions may be delivered over 30+/-10 minutes.
Other Name: Avastin
Please refer to this study by its ClinicalTrials.gov identifier: NCT01262859
|United States, Pennsylvania|
|Hillman Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15232|