Locally Advanced NSCLC Hyperfractionated RT

NCT03128008 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro00083154
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Non Small Cell Lung (NSCLC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• Overall Survival With an Accelerated and Adaptive RT Approach.

  2 years

• Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach.

  2 years

• Number of Participants With Local Control With an Accelerated and Adaptive RT Approach

  2 years

Study Arms (1)

Carboplatin/Paclitaxel with radiation therapy

EXPERIMENTAL

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; Drug: Paclitaxel; Radiation: Daily hyperfractionated radiation therapy

Interventions

Carboplatin DRUG

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.

Carboplatin/Paclitaxel with radiation therapy

Paclitaxel DRUG

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.

Carboplatin/Paclitaxel with radiation therapy

Daily hyperfractionated radiation therapy RADIATION

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.

Carboplatin/Paclitaxel with radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Prior thoracic irradiation.
• Medical contraindications to thoracic irradiation.
• Pre-existing sensory neuropathy of grade ≥ 2
• 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
• Patients with contralateral hilar involvement

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Carcinoma; Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Linda Kaltenbach, PhD
• Organization: Duke University Health System

Linda.Kaltenbach@duke.edu

(919) 681-6804

Study Officials

• Christopher Kelsey, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: April 25, 2017
• Study Start: December 7, 2017
• Primary Completion: January 16, 2019
• Study Completion: January 27, 2021
• Last Updated: May 28, 2021
• Results First Posted: February 24, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)