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

Overview

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.

Full Title of Study: “Re-Induction of a Systemic Immune Response After Initial Response With Immune Therapy With Radiotherapy in Metastatic or Locally Recurrent Lung Cancer”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 1, 2022

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

  • 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.

Arms, Groups and Cohorts

  • Experimental: 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.

Clinical Trial Outcome Measures

Primary Measures

  • Progression free survival
    • Time Frame: 3 months after end of radiotherapy
    • Progression free survival

Secondary Measures

  • Remission rate irradiated lesion
    • Time Frame: 3 months after end of radiotherapy
    • Remission rate (RECIST 1.0) of the irradiated lesion
  • Remission rate non-irradiated lesion(s)
    • Time Frame: 3 months after end of radiotherapy
    • Remission rate (RECIST 1.0) of the non-irradiated lesion(s)
  • Toxicity
    • Time Frame: 3 months after end of radiotherapy
    • Toxicity evaluation CTCAE4.0

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Maastricht Radiation Oncology
  • Collaborator
    • The Netherlands Cancer Institute
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Dirk De Ruysscher, MD, PhD, Principal Investigator, Maastro Clinic, The Netherlands

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