Re-Induction After Initial Response With Immune Therapy With Radiotherapy in Lung Cancer

Non-Small Cell Carcinoma of Lung, TNM Stage 4 Clinical Trial

Official title:

Re-Induction of a Systemic Immune Response After Initial Response With Immune Therapy With Radiotherapy in Metastatic or Locally Recurrent Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03406468
• Other study ID #: Re-Induction
• Status: Completed
• Phase: Phase 2
• Start date: July 15, 2019
• Est. completion date: March 1, 2023

Study information

• Verified date: April 2023
• Source: Maastricht Radiation Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: March 1, 2023
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Carcinoma of Lung, TNM Stage 4

Intervention

Radiation:
• Radiotherapy
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.

Locations

Country	Name	City	State
Netherlands	Zuyderland Hospital	Heerlen
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	MAATRO clinic	Maastricht

Sponsors (4)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology	Maastricht University Medical Center, The Netherlands Cancer Institute, Zuyderland Medical Centre

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Progression free survival	3 months after end of radiotherapy
Secondary	Remission rate irradiated lesion	Remission rate (RECIST 1.0) of the irradiated lesion	3 months after end of radiotherapy
Secondary	Remission rate non-irradiated lesion(s)	Remission rate (RECIST 1.0) of the non-irradiated lesion(s)	3 months after end of radiotherapy
Secondary	Toxicity	Toxicity evaluation CTCAE4.0	3 months after end of radiotherapy