NCT02945631

Quarterback 2b - Sequential Therapy With Reduced Dose Chemoradiotherapy for HPV Oropharynx Cancer

Quarterback 22: A Phase II Clinical Trial of Sequential Therapy and De-Intensified Chemoradiotherapy for Locally Advanced HPV Positive Oropharynx Cancer

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Icahn School of Medicine at Mount Sinai · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to establish the efficacy and toxicity of low dose chemoradiotherapy after induction chemotherapy in patients with locally advanced HPV+ oropharynx cancer and establish prognostic factors that would apply to help select patients for this treatment in the future.

Detailed description

In general, patients with Human Papilloma Virus Oropharynx Cancer (HPVOPC) are young and will live for prolonged periods. They are at high risk for long-term toxicity and mortality from radiotherapy. While the long-term consequences of chemotherapy for head and neck cancer are relatively constrained, high-dose radiotherapy (RT) and chemoradiotherapy (CRT) substantially impact on local tissues and organ function and result in a significant rate of late mortality and morbidity in patients. Studies are now being designed to reduce the impact of RT and CRT for patients. Identifying appropriate endpoints and study arms which will allow an early assessment of outcomes will be problematic, particularly for equivalence studies wherein survival differences are small, and where prolonged time periods and large patient numbers are necessary to accurately assess outcomes. For Sequential Therapy as given with TAX 324, 3-year PFS may be an appropriate endpoint. The same may not be possible for CRT. The best example of changing outcomes in CRT trials would be R91-11, in which a premature negative conclusion regarding the efficacy of induction therapy was published with the early analysis. Late toxicity and morbidity, a hallmark of upfront cisplatin-based CRT trials, led to equivalence between induction therapy and CRT for laryngectomy-free survival at 5 years, and more importantly a non-significant relative 10% improvement in overall survival in the PF induction arm compared to the CRT arm which included an every 3-week bolus cisplatin for 3 cycles during radiotherapy. The survival results in HPVOPC achieved in TAX 324 and preliminary data from ECOG 1308 strongly suggest that it might be possible to reduce long-term morbidity in HPVOPC and preserve survival perhaps by better patient selection and by reducing radiotherapy intensity in the context of ST for more advanced cases. Best approach of HPV-negative disease might be with novel therapies and more aggressive Sequential Therapy (ST) or CRT. Current radiation dose reduction trials are under way in ECOG, RTOG and other radiation based groups. The data from TAX 324 suggest that it is possible to reduce the radiation dose because of the superior progression free survival and the ability to select risk based CRT.

Conditions

• Locally Advanced HPV Positive Oropharynx Cancer

Interventions

Type	Name	Description
RADIATION	PTV56	total dose of 56 Gy in 2.0 Gy/fraction x 28 fractions.
RADIATION	PTV50.4	total dose of 50.4 Gy in 1.8 Gy /fraction x 28 fractions.

Timeline

• Start date: 2016-04-25
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2016-10-26
• Last updated: 2026-04-02

Locations

1 site across 1 country: United States