Carcinoma, Non Small Cell Lung (NSCLC)
Conditions
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.
Interventions
DRUGCarboplatin
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.
DRUGPaclitaxel
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.
RADIATIONDaily 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.
Sponsors
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
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. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Carboplatin/Paclitaxel With Radiation Therapy |
|---|---|
| Age, Continuous | 67.5 years STANDARD_DEVIATION 7.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 10 |
| other Total, other adverse events | 9 / 10 |
| serious Total, serious adverse events | 6 / 10 |
Outcome results
Primary
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.
Time frame: 4 weeks
Population: 8 participants have RECIST measurements available
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel With Radiation Therapy | The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy | Progressive Disease | 1 Participants |
| Carboplatin/Paclitaxel With Radiation Therapy | The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy | Stable Disease | 6 Participants |
| Carboplatin/Paclitaxel With Radiation Therapy | The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy | Partial Response | 1 Participants |
| Carboplatin/Paclitaxel With Radiation Therapy | The Metabolic Complete Response Rate, Assessed Using Interim PET-CT, in an Accelerated Fashion (2 Gy/Fraction, 6 Fractions/Week) With Concurrent Chemotherapy | Complete Response | 0 Participants |
Secondary
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.
Time frame: 2 years
Population: One participant does not have any follow up data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin/Paclitaxel With Radiation Therapy | Number of Participants With Local Control With an Accelerated and Adaptive RT Approach | 1 Participants |
Secondary
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.
Time frame: 2 years
Population: 1 participant did not have any follow up data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel With Radiation Therapy | Overall Survival With an Accelerated and Adaptive RT Approach. | NA months |
Secondary
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.
Time frame: 2 years
Population: One participant did not have any follow up data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel With Radiation Therapy | Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach. | 13.39 months |
Secondary
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.
Time frame: 4 weeks
Population: 9 participants indicated whether they had Boost or not
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin/Paclitaxel With Radiation Therapy | 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 | 3 Participants |