Clinical trial NCT03406468: Re-Induction After Initial Response With Immune Therapy With Radiotherapy in Lung Cancer
Official title: Re-Induction of a Systemic Immune Response After Initial Response With Immune Therapy With Radiotherapy in Metastatic or Locally Recurrent Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Carcinoma of Lung, TNM Stage 4
Keywords: non small cell lung cancer
immune therapy
radiotherapy
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: The Netherlands Cancer Institute
name: Maastricht University Medical Center
name: Zuyderland Medical Centre
First posted: 2018-01-23
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 3 months after end of radiotherapy
Secondary outcomes:
measure: Remission rate irradiated lesion
timeFrame: 3 months after end of radiotherapy
measure: Remission rate non-irradiated lesion(s)
timeFrame: 3 months after end of radiotherapy
measure: Toxicity
timeFrame: 3 months after end of radiotherapy
Other outcomes:
Locations:
city: Heerlen
country: Netherlands
facility: Zuyderland Hospital
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Maastricht
country: Netherlands
facility: MAATRO clinic
Study officials:
affiliation: Maastro Clinic, The Netherlands
name: Dirk De Ruysscher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: