A Randomized Phase II Trial of Concurrent Chemoradiation With Cetuximab (ERBITUX®), 5 Fluorouracil, Hydroxyurea, and Twice-daily Radiation (CetuxFHX) Versus Cetuximab (ERBITUX®), Cisplatin, and Accelerated Radiation With Concomitant Boost (CetuxPX) After Induction Chemotherapy in Patients With Locally Advanced Head and Neck Cancer
Overview
- Phase
- Phase 2
- Intervention
- Cetuximab
- Conditions
- Head and Neck Cancer
- Sponsor
- University of Chicago
- Enrollment
- 110
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The main purpose of this study is to explore and compare the efficacy of Cetuximab (ERBITUX®) added to two concurrent chemoradiotherapy platforms of different intensity in locally advanced head and neck cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 or older
- •Stage III and IV head and neck cancer
- •Patients with squamous cell carcinoma of unknown primary and suspected origin in the head and neck area
- •No prior chemotherapy or radiotherapy
- •Prior surgical therapy of incisional or excisional biopsy and organ-sparing procedures only
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
- •Normal organ and marrow function
Exclusion Criteria
- •Unequivocal demonstration of metastatic disease
- •Known severe hypersensitivity to drugs used in the study
- •Treatment with a non-approved or investigational drug within 30 days before Day 1
- •Incomplete healing from previous surgery
- •Pregnancy or breast feeding
- •Uncontrolled intercurrent illness including
- •Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF
- •Acute hepatitis or known HIV
- •Severe baseline neurologic deficits
- •Prior therapy which specifically and directly targets the EGFR pathway
Arms & Interventions
A: Cetuximab+FHX
Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
Intervention: Cetuximab
A: Cetuximab+FHX
Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
Intervention: 5-FU
A: Cetuximab+FHX
Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
Intervention: Hydroxyurea
A: Cetuximab+FHX
Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
Intervention: Twice-daily radiation
B: Cetuximab + PX
Cetuximab \[250 mg/m2 (day 1, weekly x7)\] + PX (Cisplatin \[100mg/m2 (week 1 \& 4 on day 1 (or 2))\], Accelerated fraction radiotherapy with concomitant boost \[AFX-CB (72 Gy/42 F/6 W) (3-D or IMRT based)\]). Total duration: 7 weeks.
Intervention: Cetuximab
B: Cetuximab + PX
Cetuximab \[250 mg/m2 (day 1, weekly x7)\] + PX (Cisplatin \[100mg/m2 (week 1 \& 4 on day 1 (or 2))\], Accelerated fraction radiotherapy with concomitant boost \[AFX-CB (72 Gy/42 F/6 W) (3-D or IMRT based)\]). Total duration: 7 weeks.
Intervention: Cisplatin
B: Cetuximab + PX
Cetuximab \[250 mg/m2 (day 1, weekly x7)\] + PX (Cisplatin \[100mg/m2 (week 1 \& 4 on day 1 (or 2))\], Accelerated fraction radiotherapy with concomitant boost \[AFX-CB (72 Gy/42 F/6 W) (3-D or IMRT based)\]). Total duration: 7 weeks.
Intervention: Accelerated fraction radiotherapy with concomitant boost
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: 2 years
Time from randomization until disease progression or death from any cause. Kaplan-Meier estimate of PFS at 2 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Secondary Outcomes
- Objective Response Rate to CRT(From date of chemoradiotherapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 weeks)
- Overall Survival (OS)(2 years)
- Objective Response Rate to Induction(Post-Induction (8 weeks))
- Residual Lymph Node Disease(Up to 10 weeks)