Non Small Cell Lung Cancer Metastatic
Conditions
Keywords
NSCLC, Lung Cancer, Non Small Cell Lung Cancer
Brief summary
This study includes the additional use of radiation therapy in combination immunotherapy in order to determine whether the radiation may improve the response of non-small cell lung cancer to immunotherapy and to monitor any side effects.
Detailed description
Preclinical data suggest that radiation therapy may be uniquely suited to combine with immune checkpoint inhibitors, since radiation can disrupt a tumor's physical barriers to T-cell infiltration and augment antigen presentation, thus serving as an in situ personalized vaccine to activate the immune system and potentially enhance the systemic response. The rationale for this study is to determine the safety and efficacy of combined immune checkpoint inhibitors and radiation therapy in metastatic non-small cell lung cancer patients.
Interventions
RADIATIONRadiation
Radiation therapy will be administered in 3 or 5 fractions over 3-10 days, at a recommended dose of 8-15 Gy per fraction for 3 total fractions (total dose 24-45 Gy) or 6-10 Gy per fraction for 5 total fractions (total dose 30-50 Gy)
DRUGImmuno-Therapeutic Agent
Immune checkpoint inhibitors that are FDA approved for use in patients with metastatic NSCLC will be acceptable for use concurrently with radiotherapy in this trial. The choice of agents will be at the treating medical oncologist's discretion, and include: * Nivolumab 240mg or 3 mg/kg once every 2 weeks (14 day cycle) * Pembrolizumab 200mg or 2 mg/kg once every 3 weeks (21 day cycle) * Atezolizumab 1200 mg once every 3 weeks (21 day cycle) These agents should be continued per standard of care until either disease progression or unacceptable toxicity.
Sponsors
West Virginia Clinical and Translational Science Institute
West Virginia 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
* Stage IV metastatic Non Small Cell Lung Cancer * Measurable disease of at least 1.5 cm in greatest dimension at least 2 non-irradiated sites (except for lymph nodes, in which the short-axis dimension must be at least 1.5cm). There must be at least 1 visceral organ metastasis outside of the brain. * History of prior cytotoxic chemotherapy (with or without concomitant radiation therapy) with subsequent distant (metastatic) disease relapse, or progression of disease while on chemotherapy. * Participant must be planned to receive (or actively receiving) standard of care checkpoint inhibitor immune therapy. For those patients actively receiving checkpoint inhibitor immune therapy the duration of immune therapy at the time of enrollment must be 4 months or less. * Life expectancy greater than 3 months
Exclusion criteria
* Active autoimmune disease, primary immunodeficiency syndrome, HIV/AIDS, or hepatitis B or C * Oral corticosteroid dependency * Uncontrolled or untreated active brain metastases/CNS disease * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Best Overall Response | From the start of treatment until disease progression up to 2 years. | Time to Best Overall Response is measured in months from the start of treatment until the best response is achieved. Both RECIST v1.1 and irRC criteria will be used. RECIST Criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD. Progressive Disease (PD): ≥20% increase in the sum of the diameters of target lesions or appearance of new lesions. irRC Criteria: Complete Response (irCR): Disappearance of all lesions in two consecutive observations ≥4 weeks apart. Partial Response (irPR): ≥50% decrease in tumor burden compared with baseline in two observations ≥4 weeks apart. Stable Disease (irSD): Neither sufficient decrease for irPR nor sufficient increase for irPD. Progressive Disease (irPD): ≥25% increase in tumor burden compared with nadir in two consecutive observations ≥4 weeks apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression Free Survival | From the start of treatment until the date of documented progression or death assessed up to 2 years | The duration of time from start of treatment to time of progression or death, whichever occurs first. For those patients with a CR or PR, the reference for progressive disease is the smallest measurements recorded since the treatment started. RECIST version 1.1 will be used to assess the local response of irradiated lesions only, taking as reference the baseline largest diameter: Complete Response (CR) - Disappearance of the irradiated lesion Partial Response (PR) - \> 30% decrease in the single largest diameter of the irradiated lesion Stable Disease (SD) - Neither sufficient decrease in diameter to qualify as PR nor sufficient increase in diameter to qualify as PD Progressive Disease (PD) - \> 20% increase in the single largest diameter of the irradiated lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). |
| Overall Survival | From the start of treatment until the date date of death, or the last follow up date on which the participant was reported alive, assessed up to 2 years | Amount of time from treatment until death, reported via follow up visit or phone call. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation Therapy + Immunotherapy 3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent
Radiation: Radiation therapy will be administered in 3 or 5 fractions over 3-10 days, at a recommended dose of 8-15 Gy per fraction for 3 total fractions (total dose 24-45 Gy) or 6-10 Gy per fraction for 5 total fractions (total dose 30-50 Gy)
Immuno-Therapeutic Agent: Immune checkpoint inhibitors that are FDA approved for use in patients with metastatic NSCLC will be acceptable for use concurrently with radiotherapy in this trial. The choice of agents will be at the treating medical oncologist's discretion, and include:
* Nivolumab 240mg or 3 mg/kg once every 2 weeks (14 day cycle)
* Pembrolizumab 200mg or 2 mg/kg once every 3 weeks (21 day cycle)
* Atezolizumab 1200 mg once every 3 weeks (21 day cycle)
These agents should be continued per standard of care until either disease progression or unacceptable toxicity. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Radiation Therapy + Immunotherapy |
|---|---|
| Age, Continuous | 66 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 33 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 35 |
| other Total, other adverse events | 32 / 35 |
| serious Total, serious adverse events | 25 / 35 |
Outcome results
Primary
Time to Best Overall Response
Time to Best Overall Response is measured in months from the start of treatment until the best response is achieved. Both RECIST v1.1 and irRC criteria will be used. RECIST Criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD. Progressive Disease (PD): ≥20% increase in the sum of the diameters of target lesions or appearance of new lesions. irRC Criteria: Complete Response (irCR): Disappearance of all lesions in two consecutive observations ≥4 weeks apart. Partial Response (irPR): ≥50% decrease in tumor burden compared with baseline in two observations ≥4 weeks apart. Stable Disease (irSD): Neither sufficient decrease for irPR nor sufficient increase for irPD. Progressive Disease (irPD): ≥25% increase in tumor burden compared with nadir in two consecutive observations ≥4 weeks apart.
Time frame: From the start of treatment until disease progression up to 2 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy + Immunotherapy | Time to Best Overall Response | 14 months |
Secondary
Overall Survival
Amount of time from treatment until death, reported via follow up visit or phone call.
Time frame: From the start of treatment until the date date of death, or the last follow up date on which the participant was reported alive, assessed up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy + Immunotherapy | Overall Survival | 15 months |
Secondary
Time to Progression Free Survival
The duration of time from start of treatment to time of progression or death, whichever occurs first. For those patients with a CR or PR, the reference for progressive disease is the smallest measurements recorded since the treatment started. RECIST version 1.1 will be used to assess the local response of irradiated lesions only, taking as reference the baseline largest diameter: Complete Response (CR) - Disappearance of the irradiated lesion Partial Response (PR) - \> 30% decrease in the single largest diameter of the irradiated lesion Stable Disease (SD) - Neither sufficient decrease in diameter to qualify as PR nor sufficient increase in diameter to qualify as PD Progressive Disease (PD) - \> 20% increase in the single largest diameter of the irradiated lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm).
Time frame: From the start of treatment until the date of documented progression or death assessed up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy + Immunotherapy | Time to Progression Free Survival | 6.9 Months |