Clinical trial NCT03128008: Locally Advanced NSCLC Hyperfractionated RT
Official title: Phase II Study of Accelerated and Adaptive Radiation Therapy for Locally-Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non Small Cell Lung (NSCLC)
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2017-04-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective phase II study designed to evaluate an accelerated and adaptive RT approach for locally-advanced non-small cell lung cancer (NSCLC). All eligible subjects will have an interim PET-CT during radiation therapy to determine the metabolic complete response rate. Radiation therapy will be given in an accelerated fashion (2 Gy/fraction, 6 fractions/week) with concurrent chemotherapy. Interim responses will be assessed using PERCIST criteria.

Despite concurrent chemotherapy and radiation therapy, local/regional failure occurs in \~50% of patients with locally-advanced NSCLC. Clinical studies have demonstrated that accelerated fractionation (giving the same total dose in a shorter period of time) improves outcomes in several malignancies, including lung cancer. Administering higher than conventional doses of RT to all sites of original disease leads to inferior outcomes. Adapting the RT approach, giving a higher dose to slowly responding disease as assessed with interim PET has been shown to be feasible. PERCIST (Positron Emission Tomography Response Criteria in Solid Tumors) provides guidelines on how to report responses to therapy based on PET-CT. PET-CT response has been shown to be prognostic in a variety of clinical scenarios in lung cancer including after induction therapy. In one study, PET was performed after neoadjuvant chemoradiotherapy (40-50.4 Gy). Complete or partial metabolic response using PERCIST criteria was predictive of loco-regional, distant, and overall progression-free survival.


Eligibility criteria: Inclusion Criteria:

1. Histologic/cytologic documentation of non-small cell lung cancer (NSCLC)
2. Unresectable stage II, IIIA, or IIIB disease
3. Zubrod/ECOG performance status 0-1
4. Weight loss \< 10% in preceding 3 months prior to diagnosis
5. Adequate organ function defined as the following
6. Absolute neutrophil count of ≥ 1,500 and platelet count ≥ 100,000
7. Cockcroft calculated creatinine clearance of ≥ 45 ml/min or 1.5 x the upper limit of normal (ULN)
8. A total bilirubin ≤ 1.5 ULN, aspartate aminotransferase (AST) ≤ 2.0 x ULN
9. ≥ 18 years of age.
10. Negative pregnancy test in women of child-bearing potential
11. Signed study-specific informed consent.
12. No prior chemotherapy or radiotherapy for NSCLC
13. No prior mediastinal or thoracic radiation

Exclusion Criteria:

1. Prior thoracic irradiation.
2. Medical contraindications to thoracic irradiation.
3. Pre-existing sensory neuropathy of grade ≥ 2
4. Pleural effusion: when pleural fluid is visible on both CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.

   Patients with effusions that are minimal (i.e. not visible on chest x-ray) or that are too small to safely tap are eligible
5. Patients with contralateral hilar involvement

Primary outcomes:
measure: The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy
timeFrame: 4 weeks
Secondary outcomes:
measure: The Number of Participants Eligible for an RT Boost After Completing a Standard Dose of RT (60 Gy), Delivered in an Accelerated Fashion (6 Fractions/Week) With Concurrent Chemotherapy
timeFrame: 4 weeks
measure: Overall Survival With an Accelerated and Adaptive RT Approach.
timeFrame: 2 years
measure: Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach.
timeFrame: 2 years
measure: Number of Participants With Local Control With an Accelerated and Adaptive RT Approach
timeFrame: 2 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke Health
name: Christopher Kelsey, MD
role: PRINCIPAL_INVESTIGATOR
References: