NCT02277457

Personalized Adaptive Radiation Therapy With Individualized Systemic Targeted Therapy (PARTIST) for Locally Advanced, Non-small Cell Lung Cancer With Genomic Driver Mutations

• Status: Withdrawn
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Michigan Rogel Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Hypotheses: Short-term - Targeted therapy with erlotinib or crizotinib plus PART (Personalized Adaptive Radiation Therapy) will be safe and will yield favorable outcomes in patients with stage III, EGFR (Epidermal Growth Factor Receptor) + or ALK (Anaplastic Lymphoma Kinase) + NSCLC (Non-Small Cell Lung Cancer). Long-term - In patients with stage III NSCLC harboring driver mutations, treatment with relevant targeted agents plus PART will improve both local-regional and systemic tumor control resulting in improved survival relative to standard chemoradiotherapy.

Detailed description

The proposed trial is a pilot study that will accrue 30 patients with inoperable stage IIIA/B NSCLC harboring either an EGFR mutation (n=20) or an ALK rearrangement (n=10). Patients with EGFR+ tumors will be treated with erlotinib 150 mg orally QD; patients with ALK+ tumors will be treated with crizotinib 250 mg orally BID. Treatment consists of six weeks of concurrent PART plus erlotinib or crizotinib, followed by erlotinib or crizotinib for a total of 1 year. All patients will be treated with response-driven PART with dose intensified to the active (FDG-avid) region based on a mid-treatment FDG-PET/CT scan while maintaining dose limits for organs-at-risk. The primary endpoints will be PFS and OS. Primary analyses will be performed separately for ALK+ and EGFR+ patients. The secondary endpoint of treatment-related toxicity will focus on pneumonitis and esophagitis with a strict stopping rule in place. Current standard therapy affords suboptimal outcomes for patients with locally advanced NSCLC due to both locoregional and distant recurrences. Since targeted therapy is more effective than chemotherapy in patients with relevant driver mutations, the best way to significantly improve outcomes in this subgroup of patients is to optimize systemic therapy with targeted agents while improving local control with PET-adapted, high-dose RT.

Conditions

• Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
RADIATION	PET-Adaptive RT	All patients will be treated with response-driven PET-adaptive RT. The radiation dose will be delivered in greater than or equal to 2.2 Gy per daily fraction to FDG-PET/CT-guided target volumes with the treatment duration limited to 30 fractions and total radiation dose limited to 66-80.4 Gy.
DRUG	Erlotinib	150 mg once daily
DRUG	Crizotinib	250 mg twice daily

Timeline

• Start date: 2015-09-01
• Primary completion: 2021-06-01
• First posted: 2014-10-29
• Last updated: 2016-06-24

Locations

1 site across 1 country: United States