Non-Small Cell Carcinoma of Lung, TNM Stage 4
Conditions
Keywords
non small cell lung cancer, immune therapy, radiotherapy
Brief summary
Radiotherapy in combination with different forms of immune therapy improved consistently local tumor control and very interestingly, lead to better systemic tumor control and the induction of specific anti-cancer immunity with a memory effect. In small series, it has been shown that a new long-lasting remission can be induced by irradiating one tumor site in patients who showed cancer progression after an initial response to immune therapy. In these series, the original immune therapy was continued and the treatment was very well tolerated. In this study the progression-free survival after radiotherapy to a single lesion will be investigated in patients with stage IV non-small cell lung cancer (NSCLC), who have at least achieved stable disease with immune therapy alone or concurrent immune therapy and chemotherapy.
Detailed description
Radiation has consistently been shown to activate key elements of the immune system. Radiotherapy in combination with different forms of immune therapy such as anti-PD-(L)1, anti-CTLA4,immunocytokines, dendritic cell vaccination and Toll-like receptor agonists improved consistently local tumor control and very interestingly, lead to better systemic tumor control (the abscopal effect) and the induction of specific anti-cancer immunity with a memory effect. Moreover, as PD1/PD-L1 is upregulated by radiation and radiation can overcome resistance for PD-(L)1 blockage, their combination is logical. In small series, it has been shown that a new long-lasting remission can be induced by irradiating one tumor site in patients who showed cancer progression after an initial response to immune therapy. In these series, the original immune therapy was continued and the treatment was very well tolerated. In this study the progression-free survival after radiotherapy to a single lesion will be investigated in patients with stage IV non-small cell lung cancer (NSCLC), who have at least achieved stable disease with immune therapy alone or concurrent immune therapy and chemotherapy.
Interventions
RADIATIONRadiotherapy
Patients continue the same immune therapy they already received and get radiotherapy to one lesion. The lesion may or may not be symptomatic. The preferred radiotherapy dose is 24 Gy in 3 fractions (dosage on the 10 Gy isodose is allowed), but other fractionation schedules (e.g. 30 Gy/ 10 fractions, 20 Gy/ 5 fractions, 20-24 Gy / 1 fraction for SRS (stereotactic radiosurgery)) are allowed if these are standard for a certain location or palliative indication in the body.
Sponsors
The Netherlands Cancer Institute
Maastricht University Medical Center
Zuyderland Medical Centre
Maastricht Radiation Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Given the objective of this phase II trial and the limited number of patients, no formal statistical analyses are planned. Analysis will be limited to presentation of frequencies and proportions and the report of descriptive statistics (e.g. mean, median and/or range) in tabulated form.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage IV non-small cell lung cancer * Initially a Complete Remission, Partial Remission or Stable Disease under immune therapy alone or concurrent immune therapy and chemotherapy and now progressive disease * Able to continue the immune therapy
Exclusion criteria
* Not able to continue the already initiated immune therapy * Patients with any grade 3 toxocity * Patients in whom radiotherapy cannot be delivered, according to the radiation oncologist at the multi-disciplinary patient discussion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | 3 months after end of radiotherapy | Progression free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission rate irradiated lesion | 3 months after end of radiotherapy | Remission rate (RECIST 1.0) of the irradiated lesion |
| Remission rate non-irradiated lesion(s) | 3 months after end of radiotherapy | Remission rate (RECIST 1.0) of the non-irradiated lesion(s) |
| Toxicity | 3 months after end of radiotherapy | Toxicity evaluation CTCAE4.0 |
Countries
Netherlands
Outcome results
None listed