Non-Small Cell Lung Cancer
Conditions
Keywords
Radiation Treatment, SBRT, ChemoImmunotherapy
Brief summary
The purpose of this research study is to find out if adding radiation prior to chemoimmunotherapy and surgery is effective for people with non-small cell lung cancer (NSCLC) who have the potential for surgery. Standard of Care Chemoimmunotherapy: For this study, standard of care chemotherapy will be used. This means this is the type of chemotherapy that is normal for your cancer. In addition to the chemotherapy, you will also receive the immunotherapy drug, nivolumab. This will be administered intravenously once every 3 weeks for up to 3 cycles (i.e. 9 weeks of total systemic therapy), prior to surgical resection assessment. This combination is made up of the chemotherapy drugs carboplatin or cisplatin along with pemetrexed, paclitaxel or gemcitabine, and the immunotherapy drug is nivolumab. The chemotherapy is used to kill cancer cells, and the immunotherapy enables your immune system to attack cancer cells. Stereotactic Body Radiation Therapy (SBRT) SBRT is when radiation is delivered at higher doses over a smaller period of time. For this study, you will receive three doses of radiation delivered every other day, for three total days. The final dose of radiation will happen within 7 days of starting chemoimmunotherapy. You will be followed for up to 100 days following your last chemoimmunotherapy dose to monitor for potential side effects. Following this you will continue with your standard follow up with your doctor. During the standard follow-up time, study staff will review your charts to see if there have been any new updates with your cancer following treatment so they can tell how this treatment affects how long patients live and whether it helps avoid recurrence of the cancer.
Interventions
DRUGNivolumab
This will be administered intravenously once every 3 weeks for up to 3 cycles (i.e. 9 weeks of total systemic therapy)
DRUGChemotherapy
Chemotherapy options include: carboplatin or cisplatin along with pemetrexed, paclitaxel or gemcitabine
RADIATIONSBRT
Three fractions of radiation delivered every other day, for three total days. The final dose of radiation will happen within 7 days of starting chemoimmunotherapy
PROCEDURESurgical Resection
Post treatment patient will be evaluated for surgical resection
Sponsors
University of Maryland, Baltimore
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. Age greater than or equal to18 years at time of study entry 2. Eastern cooperative oncology group (ECOG) performance status of 0 or 1 3. Participants with histologically confirmed stage II-IIIC(N3) NSCLC (per the 8th International Association for the Study of Lung Cancer) with disease that is considered borderline resectable prior to initiation of RT or systemic therapy. a. Patients with intrathoracic, contralateral N3 disease will be allowed to enroll (see
Exclusion criteria
for further details) 4. Subject cases must be reviewed in a multidisciplinary thoracic tumor board setting prior to enrollment to allow for adequate discussion regarding the potential for resection. 5. Participants must have a tumor tissue sample available for biomarker testing, including next-generation sequencing to confirm EGFR/ALK status. Assessment of EGFR/ALK status may be performed locally through a CLIA approved laboratory testing method. a. Tissue source may be a formalin fixed paraffin block (FFPE) of a previous tumor biopsy sample. Source of biomarker testing may be obtained from archived tissue if adequate or from a new biopsy, if needed and clinically indicated 6. Absence of major associated pathologies that increase the surgery risk to an unacceptable level 7. Pulmonary function capacity (eg. FVC, FEV1, TLC, and DLCO) capable of tolerating proposed lung resection according to surgeon. 8. Adequate normal organ and marrow function defined below: 1. Platelet count greater than or equal to100,000/mm3 2. Hemoglobin greater than or equal to 8 g/dL 3. Absolute neutrophil count (ANC) greater than or equal to 1000/mm3 4. Creatinine less than or equal to 1.5 x ULN or creatinine clearance (CrCl) greater than or equal to 40 mL/min 5. Total bilirubin less than or equal to 1.5 x ULN (except subjects with Gilbert Syndrome who can have total bilirubin \< 3.0 mg/dL) 6. AST, ALT, Alkaline phosphatase less than or equal to 3 x ULN per local testing 9. Subjects are deemed capable of giving informed consent and must have signed and dated an IRB approved written informed consent form. This written consent must be obtained before the performance of any protocol related procedures that are not part of normal standard of care. 10. Women of childbearing potential (WOCBP) must have negative serum or urine pregnancy testing within 30 days of study start.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of Adding Sub-ablative, Immunosensitizing, Radiotherapy to Standard of Care Neoadjuvant Chemoimmunotherapy | 20 weeks post initiation of neoadjuvant therapy | Evaluate the tolerability of adding sub-ablative, immunosensitizing, radiotherapy to standard of care neoadjuvant chemoimmunotherapy prior to surgery for resectable NSCLC, measured by the rate of DLTs from time of neoadjuvant therapy initiation to start of definitive therapy (either surgery or chemoimmunotherapy initiation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events assessment by CTCAE v5.0 that are related to treatment | 20-22 weeks post initiation of neoadjuvant therapy | Determine the safety of adding sub-ablative, immunosensitizing, radiotherapy to standard of care neoadjuvant chemoimmunotherapy prior to definitive resection for resectable NSCLC, measured by the frequency of drug related adverse events, including serious adverse events, occurring up to the initiation of definitive therapy (either surgery or chemoimmunotherapy initiation). Safety will be measured by the frequency of drug related adverse events, including serious adverse events (defined by CTCAE version 5), occurring up until the time of definitive therapy initiation (either surgery or chemoradiotherapy). |
| Pathologic Complete Response Rate (pCR) | 20-22 weeks post initiation of neoadjuvant therapy | Estimate the rate of pathologic complete response after adding immunosensitizing radiotherapy to neoadjuvant chemoimmunotherapy prior to definitive resection. pCR is defined as lack of any viable tumor cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes as determined by central pathology review and described by IASLC 2020 assessment criteria. The measure of interest is the proportion of resected patients with 0% residual viable tumor cells within all resected tissue as assessed by the central pathology review. |
| Major Pathologic Response Rate (MPR) | 20-22 weeks post initiation of neoadjuvant therapy | Estimate the rate of major pathologic response after adding immunosensitizing radiotherapy to neoadjuvant chemoimmunotherapy prior to definitive resection. MPR is defined as ≤ 10% viable tumor cells in resected tumor after complete evaluation in the resected lung cancer specimen as determined by central pathology review and described by IASLC 2020 assessment criteria. The measure of interest is the proportion of resected patients with ≤ 10% residual viable tumor cells within all resected tissue as assessed by the central pathology review. |
| Measure rate of definitive resection | 1 year post completion of accrual | Establish the rate of definitive resection for patients with borderline resectable NSCLC treated with subablative radiotherapy followed by neoadjuvant chemoimmunotherapy. Rate of definitive resection will be measured as the percentage of participants who undergo a complete R0 resection of their disease after receiving neoadjuvant subablative radiotherapy followed by chemoimmunotherapy out of all treated participants. |
Countries
United States
Contacts
CONTACTMatthew Ferris, MD
CONTACTCaitlin Eggleston, MPH
Outcome results
None listed