Locally Advanced NSCLC Hyperfractionated RT (ADAPT)

• ClinicalTrials.gov Identifier: NCT03128008
• Recruitment Status: Active, not recruiting
• First Posted: April 25, 2017
• Results First Posted: February 24, 2020
• Last Update Posted: February 24, 2020
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non Small Cell Lung (NSCLC)	Drug: Carboplatin; Drug: Paclitaxel; Radiation: Daily hyperfractionated radiation therapy	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Accelerated and Adaptive Radiation Therapy for Locally-Advanced Non-Small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: December 7, 2017
• Actual Primary Completion Date: January 16, 2019
• Estimated Study Completion Date: January 16, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy [ Time Frame: 4 weeks ]
   For the cohort of the subjects 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 :

1. The Number of Subjects 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 [ Time Frame: 4 weeks ]
   In the same subject cohort, the proportion of the subjects 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.
2. Overall Survival With an Accelerated and Adaptive RT Approach. [ Time Frame: 2 years ]
   The overall survival (OS) for the treated subjects will be characterized by Kalan-Meier estimator. The medial OS will be estimated with a 95% confidence interval.
3. Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach. [ Time Frame: 2 years ]
   Median progression-free survival for subjects will be characterized by Kalan-Meier estimator. The median PFS will be estimated as well as their 95% confidence intervals.
4. Local Control With an Accelerated and Adaptive RT Approach [ Time Frame: 2 years ]
   The local control rate for the same cohort of subjects will be measured by standard of care imaging per NCCN guidelines at routine follow up clinic visits.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: Christopher Kelsey, MD; Duke University Health System

  Study Documents (Full-Text)

Documents provided by Duke University:

Study Protocol and Statistical Analysis Plan  [PDF] August 7, 2018

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03128008
• Other Study ID Numbers: Pro00083154
• First Posted: April 25, 2017
• Results First Posted: February 24, 2020
• Last Update Posted: February 24, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Paclitaxel; Carboplatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action