Non-Small Cell Carcinoma of Lung, TNM Stage 4Phase 2NCT03406468
Re-Induction After Initial Response With Immune Therapy With Radiotherapy in Lung Cancer
A Phase 2 study testing Radiotherapy in people with Non-Small Cell Carcinoma of Lung, TNM Stage 4, run by Maastricht Radiation Oncology at 3 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Carcinoma of Lung, TNM Stage 4
- What is being tested?
- Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 3 sitesNetherlands
- Study dates
- 15 Jul 2019to 1 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Zuyderland Hospital
Heerlen, 6419 PC
Maastricht University Medical Center
Maastricht, 6202 AZ
MAATRO clinic
Maastricht, 6229 ET
About this study
Official title: Re-Induction of a Systemic Immune Response After Initial Response With Immune Therapy With Radiotherapy in Metastatic or Locally Recurrent Lung Cancer
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.
Read the 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.
- Being tested
- Radiotherapy
- Keywords
- non small cell lung cancer, immune therapy, radiotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy | Experimental | 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. Receives: Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Progression free survival
Measured: 3 months after end of radiotherapy
Secondary outcomes (3)
Remission rate irradiated lesion
Remission rate (RECIST 1.0) of the irradiated lesion
Measured: 3 months after end of radiotherapy
Remission rate non-irradiated lesion(s)
Remission rate (RECIST 1.0) of the non-irradiated lesion(s)
Measured: 3 months after end of radiotherapy
Toxicity
Toxicity evaluation CTCAE4.0
Measured: 3 months after end of radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start15 Jul 2019
- Primary completion1 Aug 2022
- Study completion1 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Carcinoma of Lung, TNM Stage 4Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht Radiation Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- The Netherlands Cancer Institute, Maastricht University Medical Center, Zuyderland Medical Centre
- Responsible party
- Sponsor
- Investigators
- Dirk De Ruysscher, MD, PhD, Principal investigator, Maastro Clinic, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03406468
- Sponsor's protocol ID
- Re-Induction
- Status last verified
- Apr 2023
- First submitted
- 15 Jan 2018
- Last updated
- 4 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Re-Induction of a Systemic Immune Response After Initial Response With Immune Therapy With Radiotherapy in Metastatic or Locally Recurrent Lung Cancer
- ClinicalTrials.gov ID
- NCT03406468
- Acronym / sponsor ID
- Re-Induction
- Keywords
- non small cell lung cancer, immune therapy, radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Maastricht Radiation OncologyUniversity, hospital or other
- Collaborators
- The Netherlands Cancer Institute, Maastricht University Medical Center, Zuyderland Medical Centre
- Study start
- 15 Jul 2019 (actual)
- Primary completion
- 1 Aug 2022 (actual)
- Study completion
- 1 Mar 2023 (actual)
- First posted
- 23 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy | Experimental | Radiation: RadiotherapyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RadiotherapyPatients 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. | Radiation | Radiotherapy |
Primary outcome
Progression free survival
Time frame: 3 months after end of radiotherapy
Progression free survival
3 secondary outcomes
Remission rate irradiated lesion
Time frame: 3 months after end of radiotherapy
Remission rate non-irradiated lesion(s)
Time frame: 3 months after end of radiotherapy
Toxicity
Time frame: 3 months after end of radiotherapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dirk De Ruysscher, MD, PhD principal investigator
Maastro Clinic, The Netherlands
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiotherapy in people with Non-Small Cell Carcinoma of Lung, TNM Stage 4, run by Maastricht Radiation Oncology at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 3 months after end of radiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2023; AzTrials last refreshed its copy on 31 Oct 2026.