Locally Advanced NSCLC Hyperfractionated RT

Phase 2

Completed

• Conditions: Carcinoma, Non Small Cell Lung (NSCLC)
• Interventions: Drug: Carboplatin; Drug: Paclitaxel; Radiation: Daily hyperfractionated radiation therapy

• Registration Number: NCT03128008
• Lead Sponsor: Duke University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-18
• Study First Submitted QC: 2017-04-24
• Study First Posted: 2017-04-25
• Study Start: 2017-12-07
• Primary Completion: 2019-01-16
• Results First Submitted: 2020-01-16
• Results First Submitted QC: 2020-02-11
• Results First Posted: 2020-02-24
• Study Completion: 2021-01-27
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-05
• Last Update Posted: 2021-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Carboplatin/Paclitaxel with radiation therapy	Daily hyperfractionated radiation therapy	Single arm, non randomized, open label study. Eligible subjects will receive standard of care Carboplatin IV once a week, Paclitaxel IV once a week given concurrently with daily hyperfractionated radiation therapy (RT). RT will be delivered as 6 fractions weekly.
Carboplatin/Paclitaxel with radiation therapy	Paclitaxel	Single arm, non randomized, open label study. Eligible subjects will receive standard of care Carboplatin IV once a week, Paclitaxel IV once a week given concurrently with daily hyperfractionated radiation therapy (RT). RT will be delivered as 6 fractions weekly.
Carboplatin/Paclitaxel with radiation therapy	Carboplatin	Single arm, non randomized, open label study. Eligible subjects will receive standard of care Carboplatin IV once a week, Paclitaxel IV once a week given concurrently with daily hyperfractionated radiation therapy (RT). RT will be delivered as 6 fractions weekly.

Primary Outcome Measures

Name	Time	Method
The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy	4 weeks	For the cohort of the participants who meet eligibility criteria and receive radiotherapy with concurrent chemotherapy, the metabolic complete response (MCR) rate will be measured with interim PET-CT utilizing PERCIST response reporting criteria.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Local Control With an Accelerated and Adaptive RT Approach	2 years	The local control rate for the same cohort of participants will be measured by standard of care imaging per NCCN guidelines at routine follow up clinic visits.
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	4 weeks	In the same participant cohort, the proportion of the participants who are 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, will be estimated as well as its confidence interval.
Overall Survival With an Accelerated and Adaptive RT Approach.	2 years	The overall survival (OS) for the treated participants will be characterized by Kaplan-Meier estimator. The medial OS will be estimated with a 95% confidence interval.
Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach.	2 years	Median progression-free survival for participants will be characterized by Kaplan-Meier estimator. The median PFS will be estimated as well as their 95% confidence intervals.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States