Locally Advanced NSCLC Hyperfractionated RT (ADAPT)

Phase II Study of Accelerated and Adaptive Radiation Therapy for Locally-Advanced Non-Small Cell Lung Cancer (NSCLC)

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non Small Cell Lung (NSCLC)
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Radiation: Daily hyperfractionated radiation therapy

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Carboplatin/Paclitaxel with 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.

Drug: Carboplatin; Single arm non randomized open label study. Subjects will receive standard of care Carboplatin IV once a week. Chemotherapy is given concurrently with daily hyperfractioned radiation therapy.; Drug: Paclitaxel; Single arm non randomized open label study. Subjects will receive standard of care Paclitaxel IV once a week. Chemotherapy is given concurrently with daily hyperfractioned radiation therapy.; Radiation: Daily hyperfractionated radiation therapy; All subjects will receive 6 fractions(2Gy per fraction) of radiation therapy weekly. All subjects will complete an interim PET-CT after 48Gy-54Gy of RT . Subjects with a complete response on PET will complete RT at 60 Gy; subjects who have residual disease on interim PET and meet strict planning constraints eligibility will proceed to boost RT for a total RT dose of 72Gy. Interim PET-CT response will be measured using PERCIST criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy	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.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	4 weeks
Overall Survival With an Accelerated and Adaptive RT Approach.	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.	2 years
Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach.	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.	2 years
Number of Participants With Local Control With an Accelerated and Adaptive RT Approach	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.	2 years

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Christopher Kelsey, MD, Duke Health

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2017
• Primary Completion (Actual): January 16, 2019
• Study Completion (Actual): January 27, 2021

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: Pro00083154

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No