Lung Cancer, Metastatic Lung Cancer, Non-small Cell Lung Cancer, NSCLC
Conditions
Brief summary
Nivolumab releases the inhibition of the immune system against human cancers. Dramatic and sustained activity has been observed in advanced lung cancer. Ablation may stimulate the immune system by exposing new tumor antigens. Since tumors that express PD-L1 may be more likely to respond to nivolumab, if ablation increases PD-L1 expression (which has not been studied) this treatment may enhance the activity of nivolumab at both the treated site and in other, non-treated, tumors. Ablation is already an FDA approved treatment for cancer. Nivolumab was recently FDA approved for second line treatment of advanced squamous cell NSCLC. The goal of the study will be to determine if the combination of nivolumab and ablation has higher systemic activity than previously reported with nivolumab alone.
Detailed description
See summary above
Interventions
DRUGnivolumab and ablation
Sponsors
Rhode Island Hospital
The Miriam Hospital
howard safran
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
* Pathologically or cytologically confirmed NSCLC * Stage IIIB or stage IV. * Patient to meet either criterion A or B: A) Progression after at least 1 line of systemic treatment (IV or oral) for metastatic or locally advanced disease. Must provide documentation systemic treatment was for either locally advanced or metastatic and also scan or assessment to show progression. Radiation does not count as 1 line. B) Patients progressing within 6 months of completion of neoadjuvant or adjuvant chemotherapy are also eligible without having treatment for metastatic disease (for example patient with stage I disease undergoes resection, receives systemic chemotherapy and then progresses to the liver (now stage IV) within 6 months of chemotherapy). Radiation does not count as 1 line. * Ablation for advanced lung cancer is being considered by the treating physician for treatment or prevention of symptoms such as pain, bleeding or obstruction- Documentation is required in writing by MD for this criterion. * At least 1 site of measurable disease that will not be treated with ablation. Sites to send confirmation on which lesion of measurable disease will not be ablated for tracking of response. * At least 3 weeks since prior chemotherapy and radiation therapy * No brain metastases except for patients whose metastases have been removed by surgical resection or have had stereotactic radiation or gamma knife with no evidence of active disease on MRI within 28 days of starting treatment. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. * Life expectancy of at least 12 weeks. * Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥ 1000/µl; platelet count ≥75,000/µl; absolute lymphocyte count ≥ 500/ µl; Creatinine ≤ 1.5x upper limit normal mg/dl; Bilirubin \< 1.5x upper limit normal; AST ≤ 3 x upper limit of normal. * Age \> 18 years * Men and women of childbearing potential enrolled in this study must agree to use adequate barrier birth control measures during the course of the study and up to 2 months after. * Written informed consent.
Exclusion criteria
* Patients with a history of clinically significant chronic autoimmune disease * Prior therapy with antibodies that modulate T-cell function defined as anti-CTLA-4, anti-PD-1, and anti-PD-L1 * Conditions currently requiring immunosuppressive medications * Known history of HIV or hepatitis B or C * Bleeding diathesis or coagulopathy that in the investigators opinion would prevent ablation from being safely performed. * Patients with unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months. * History of organ allograft even if not taking immunosuppressive medications * Pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate of the Combination of Ablation and the PD-1 Inhibitor Nivolumab for Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Progressed Following at Least 1 Prior Chemotherapy Regimen for Metastatic or Locally Advanced Disease. | Up to 5 years. | Assessment of tumor response by scan 12 weeks post the first dose of Nivolumab and approximately every 12 weeks after. Post progression by RECIST a 1 month confirmatory scan will be done and that will be the indicator of Progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab With Ablation 3mg/kg IV over 60 minutes on Day 1 +/- 3 days every 2 weeks until progression for a maximum of 2 years.
Either cryoablation or thermal ablation may be performed as per standard institutional policies
nivolumab and ablation | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Nivolumab With Ablation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 64.6 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 2 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 5 / 10 |
Outcome results
Primary
Response Rate of the Combination of Ablation and the PD-1 Inhibitor Nivolumab for Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Progressed Following at Least 1 Prior Chemotherapy Regimen for Metastatic or Locally Advanced Disease.
Assessment of tumor response by scan 12 weeks post the first dose of Nivolumab and approximately every 12 weeks after. Post progression by RECIST a 1 month confirmatory scan will be done and that will be the indicator of Progression.
Time frame: Up to 5 years.
Population: Number of patients that were not known to Progress
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nivolumab With Ablation | Response Rate of the Combination of Ablation and the PD-1 Inhibitor Nivolumab for Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Progressed Following at Least 1 Prior Chemotherapy Regimen for Metastatic or Locally Advanced Disease. | 1 Participants |