Locally Advanced Non Small Cell Lung CancerPhase 3TRAILOCLORI01NCT05111197
Local Ablative Stereotactic Radiotherapy for Residual Hypermetabolic Lesion in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer Long-term Responders to Immunotherapy
A Phase 3 study testing SRT and Immunotherapy in people with Locally Advanced Non Small Cell Lung Cancer and Metastatic Non Small Cell Lung Cancer, run by Institut Cancerologie de l'Ouest at 5 sites in France.
Trial summary
At present, it is recommended to continue immunotherapy until progression or unacceptable toxicity. However, only a minority of patients benefits from a durable response and most see the disease progress despite several months of control under immunotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Non Small Cell Lung Cancer, Metastatic Non Small Cell Lung Cancer
- What is being tested?
- SRT and Immunotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 5 sitesFrance
- Study dates
- 12 Jan 2022to Jan 2025
- Phase
- Phase 3
- 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
- Patient aged 18 or more,
- Patient treated for histologically proven non-small cell lung cancer,
- Stage IIIB or IV,
- Performance status 0 to 2,
- Patient treated by immunotherapy (anti PD-1 or anti PD-L1) started for at least 6 months and regardless of the treatment line (in first line, immunotherapy may have been combined with chemotherapy),
- Response or stable disease on thoraco abdomino pelvic and cerebral CT scan,
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- Maximum 5 residual hypermetabolic lesions measured on the 18F-FDG PET / CT centrally reviewed, including primary tumor and a maximum of 3 asymptomatic brain metastases (even if they are poorly seen in 18F- FDG PET/CT) treatable in stereotactic radiotherapy (extracerebral lesions ≤ 4cm and brain lesions ≤ 3cm measured on CT scanners)
- Effective contraception used in women of childbearing potential
- Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations,
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up,
- Patient has valid health insurance.
Who cannot join
- Persistence of grade 2 or greater adverse effects of immunotherapy,
- Infection in progress,
- At least one of the 5 hypermetabolic lesions measured on the 18F-FDG PET / CT centrally reviewed in a previously irradiated area,
- Uncontrolled severe comorbidity,
- History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥ 3 years and of low potential risk for recurrence ; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease ; Adequately treated carcinoma in situ without evidence of disease
- Pregnant or nursing patient
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- Patient deprived of liberty or under guardianship,
- Patient unable to undergo regular medical check-ups for geographical, social or psychological reasons.
- Disorder precluding understanding of trial information or informed consent
Trial locations and contacts
5 sites in 1 country.
Emilie DEBEAUPUIS contact
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
ICO - Site Paul Papin
Angers, 49055
HIRET SANDRINE, MD, sandrine.hiret@ico.unicancer.fr
- Not yet recruiting
Chu de Brest
Brest, 29200
Francois LUCIA, MD, Francois.lucia@chu-brest.fr
- Not yet recruiting
Centre François BACLESSE
Caen, 14000
Delphine LEROUGE, MD, d.lerouge@baclesse.unicancer.fr
- Recruiting
Institut de cancérologie de l'ouest
Saint-Herblain, 44805
Sandrine HIRET, MD, sandrine.hiret@ico.unicancer.fr
- Not yet recruiting
Chu de Tours
Tours, 37044
Nicolas MILHADE, MD, n.milhade@chu-tours.fr
About this study
Official title: Local Ablative Stereotactic Radiotherapy for Residual Hypermetabolic Lesion in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer Long-term Responders to Immunotherapy : a Randomized, Multicenter, Open-label Phase III Study
At present, it is recommended to continue immunotherapy until progression or unacceptable toxicity.
However, only a minority of patients benefits from a durable response and most see the disease progress despite several months of control under immunotherapy. Multimodal approaches have been developed to improve their prognosis.
This study, randomized, open-label study aims to evaluate the impact of addition of ablative radiotherapy on OS of patients with NSCLC and oligometastatic lesions and treated by immunotherapy in first line (potentially associated with chemotherapy) or beyond. Stereotactic radiotherapy will be performed on a maximum of 5 residual hypermetabolic lesions seen on 18F-FDG PET / CT, in patients responding to immunotherapy (or with a stable disease) for at least 6 months.
Read the detailed description
Description of the modalities for recruiting :
During a standard consultation, the oncologist presents the study to the patient with locally advanced or metastatic non-small cell lung cancer long-term responders to immunotherapy. He gives the patient the consent form to participate in the study.
Once the consent form has been signed by the patient and the investigator, the investigator prescribes a screening test which must be carried out within 30 days before the randomization (Day 0, D0).
The screening step includes in particular a complete physical exam, a clinical laboratory tests a thoraco abdomino pelvic (TAP) and cerebral CT scan, a cerebral MRI (for patients with cerebral lesions observed on cerebral CT scan), a Spinal MRI (for patients with bones lesions observed on TAP CT scan), a PET scan (18F-FDG) (the results will be routinely interpreted in the centre and will be centrally reviewed), Patient Reported Outcome (PRO), QLQ-C30 and QLQ LC13
The inclusion of a patient is conditioned by the following definitive criterion : Maximum 5 residual hypermetabolic lesions measured on the CT from the 18F-FDG PET / CT centrally reviewed, including primary tumor and a maximum of 3 brain asymptomatic metastases (even if they are poorly seen in 18F- FDG PET/CT) treatable in stereotactic radiotherapy.
Patients registration and randomization :
Any patient who has signed an informed consent form (ICF) must be registered in the eCRF in order to be assigned a patient number.
Randomization will be centralized and performed via the eCRF. Patients will be randomly assigned (1:1) to either continuation of immunotherapy alone or addition of local ablative radiotherapy to immunotherapy.
The randomization procedure using minimization method will be stratified by the investigation center, by the treatment line (1 vs ≥2) and by the immunotherapy (pembrolizumab and nivolumab versus atezolizumab).
Treatment period :
Both arms continue the anti-PD1 or anti-PDL-1 immunotherapy according to the medical prescription.
Arm A (experimental), SRT start maximum 3 weeks after randomisation
Follow-up visits include in particular a complete physical exam, a clinical laboratory tests, a thoraco abdomino pelvic and cerebral CT scan, a cerebral MRI (for patients with cerebral lesions observed on cerebral CT scan), a Spinal MRI (for patients with bones lesions observed on TAP CT scan), a PET scan (18F-FDG) at 6 months post-randomization only (the results will be routinely interpreted in the centre and will be centrally reviewed) ; Patient Reported Outcome (PRO), QLQ-C30 and QLQ LC13
Imaging surveillance (CT scan +/- cerebral MRI +/- spinal MRI) will be performed for each patient up to progression or up to 12 months after randomization of the last patient included in the absence of progression.
Vital status is collected once a year and also date of death if applicable for each patient up to 12 months after randomization of the last patient included.
- Being tested
- SRT, Immunotherapy
- Keywords
- lung, Immunotherapy, Stereotactic radiotherapy, 18F- FDG PET/ CT, Locally advanced cancer, Metastatic cancer, Overall survival, Progression Free Survival
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRTRadiation
Patients with a maximum of 5 residual hypermetabolic lesions observed on 18F- FDG PET / CT after a minimum of 6 months of immunotherapy are treated with SRT, in addition to their anti-PD-1 or anti-PD-L1 immunotherapy as it was administered before randomization in the trial, according to the standards.
A maximum of 3 Brain metastases treatable in stereotactic radiotherapy will be included among these hypermetabolic lesions.
Each lesion is treated with a total dose of 24 Gy delivered in 3 fractions of 8 Gy (isodose surface).
ImmunotherapyDrug
Patients with a maximum of 5 residual hypermetabolic lesions observed on 18F- FDG PET / CT after a minimum of 6 months of immunotherapy continue their anti-PD-1 or anti-PD-L1 immunotherapy as it was administered before randomization in the trial, according to the standards.
| Study group | Role | What they receive |
|---|---|---|
| A. (Immunotherapy + SRT) | Experimental | Continuation of anti-PD-1 or anti-PD-L1 immunotherapy, started at least 6 months ago, associated with Stereotactic Radiation Therapy (SRT) Receives: Radiation: SRT; Drug: Immunotherapy |
| B (Immunotherapy alone) | Active comparator | Continuation of anti-PD-1 or anti-PD-L1 immunotherapy alone (started at least 6 months ago) Receives: Drug: Immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
The overall survival (OS) benefit of local treatment by stereotactic radiotherapy with immunotherapy versus immunotherapy alone
Overall survival rate, where OS is the time between randomization and death of any cause
Measured: 12 months post-randomization
Secondary outcomes (6)
Overall survival (OS)
Median overall survival at the end of the study
Measured: 12 months after randomization of the last patient included
Progression Free Survival (PFS)
Median PFS, time between randomization and progression or death in absence of progression, at the end of the study
Measured: 12 months after randomization of the last patient included
Quality of life (Qol)
EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30)
Measured: 12 months after randomization
Quality of life (Qol)
Lung cancer-specific Quality of Life Questionnaire EORTC QLQ-LC13
Measured: 12 months after randomization
Overall survival (OS) in patients with complete metabolic response rate on 18F- FDG PET / CT 6 months after randomization
Median overall survival at the end of the study in patients with complete metabolic response rate on 18F- FDG PET / CT (PERSIST)
Measured: 6 months after randomization in the SRT arm
Progression Free Survival (PFS) according to complete metabolic response rate on 18F- FDG PET / CT 6 months after randomization
Median PFS at the end of the study in patients with complete metabolic response rate on 18F- FDG PET / CT (PERSIST) 6 months after randomization in the SRT arm
Measured: 6 months after randomization in the SRT arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2021
- Study start12 Jan 2022
- Primary completionJan 2025 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Non Small Cell Lung CancerStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Cancerologie de l'Ouest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05111197
- Sponsor's protocol ID
- ICO-2021-08
- Acronym
- TRAILOCLORI01
- Status last verified
- Feb 2022
- First submitted
- 27 Oct 2021
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Local Ablative Stereotactic Radiotherapy for Residual Hypermetabolic Lesion in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer Long-term Responders to Immunotherapy : a Randomized, Multicenter, Open-label Phase III Study
- ClinicalTrials.gov ID
- NCT05111197
- Acronym / sponsor ID
- TRAILOCLORI01 / ICO-2021-08
- Keywords
- lung, Immunotherapy, Stereotactic radiotherapy, 18F- FDG PET/ CT, Locally advanced cancer, Metastatic cancer, Overall survival, Progression Free Survival
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Institut Cancerologie de l'OuestUniversity, hospital or other
- Study start
- 12 Jan 2022 (actual)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 8 Nov 2021 (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.
At present, it is recommended to continue immunotherapy until progression or unacceptable toxicity.
However, only a minority of patients benefits from a durable response and most see the disease progress despite several months of control under immunotherapy. Multimodal approaches have been developed to improve their prognosis.
This study, randomized, open-label study aims to evaluate the impact of addition of ablative radiotherapy on OS of patients with NSCLC and oligometastatic lesions and treated by immunotherapy in first line (potentially associated with chemotherapy) or beyond. Stereotactic radiotherapy will be performed on a maximum of 5 residual hypermetabolic lesions seen on 18F-FDG PET / CT, in patients responding to immunotherapy (or with a stable disease) for at least 6 months.
Detailed description
Description of the modalities for recruiting :
During a standard consultation, the oncologist presents the study to the patient with locally advanced or metastatic non-small cell lung cancer long-term responders to immunotherapy. He gives the patient the consent form to participate in the study.
Once the consent form has been signed by the patient and the investigator, the investigator prescribes a screening test which must be carried out within 30 days before the randomization (Day 0, D0).
The screening step includes in particular a complete physical exam, a clinical laboratory tests a thoraco abdomino pelvic (TAP) and cerebral CT scan, a cerebral MRI (for patients with cerebral lesions observed on cerebral CT scan), a Spinal MRI (for patients with bones lesions observed on TAP CT scan), a PET scan (18F-FDG) (the results will be routinely interpreted in the centre and will be centrally reviewed), Patient Reported Outcome (PRO), QLQ-C30 and QLQ LC13
The inclusion of a patient is conditioned by the following definitive criterion : Maximum 5 residual hypermetabolic lesions measured on the CT from the 18F-FDG PET / CT centrally reviewed, including primary tumor and a maximum of 3 brain asymptomatic metastases (even if they are poorly seen in 18F- FDG PET/CT) treatable in stereotactic radiotherapy.
Patients registration and randomization :
Any patient who has signed an informed consent form (ICF) must be registered in the eCRF in order to be assigned a patient number.
Randomization will be centralized and performed via the eCRF. Patients will be randomly assigned (1:1) to either continuation of immunotherapy alone or addition of local ablative radiotherapy to immunotherapy.
The randomization procedure using minimization method will be stratified by the investigation center, by the treatment line (1 vs ≥2) and by the immunotherapy (pembrolizumab and nivolumab versus atezolizumab).
Treatment period :
Both arms continue the anti-PD1 or anti-PDL-1 immunotherapy according to the medical prescription.
Arm A (experimental), SRT start maximum 3 weeks after randomisation
Follow-up visits include in particular a complete physical exam, a clinical laboratory tests, a thoraco abdomino pelvic and cerebral CT scan, a cerebral MRI (for patients with cerebral lesions observed on cerebral CT scan), a Spinal MRI (for patients with bones lesions observed on TAP CT scan), a PET scan (18F-FDG) at 6 months post-randomization only (the results will be routinely interpreted in the centre and will be centrally reviewed) ; Patient Reported Outcome (PRO), QLQ-C30 and QLQ LC13
Imaging surveillance (CT scan +/- cerebral MRI +/- spinal MRI) will be performed for each patient up to progression or up to 12 months after randomization of the last patient included in the absence of progression.
Vital status is collected once a year and also date of death if applicable for each patient up to 12 months after randomization of the last patient included.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A. (Immunotherapy + SRT) | Experimental | Radiation: SRT, Drug: ImmunotherapyContinuation of anti-PD-1 or anti-PD-L1 immunotherapy, started at least 6 months ago, associated with Stereotactic Radiation Therapy (SRT) |
| B (Immunotherapy alone) | Active comparator | Drug: ImmunotherapyContinuation of anti-PD-1 or anti-PD-L1 immunotherapy alone (started at least 6 months ago) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patient aged 18 or more,
- Patient treated for histologically proven non-small cell lung cancer,
- Stage IIIB or IV,
- Performance status 0 to 2,
- Patient treated by immunotherapy (anti PD-1 or anti PD-L1) started for at least 6 months and regardless of the treatment line (in first line, immunotherapy may have been combined with chemotherapy),
Key exclusion criteria (9 listed)
- Persistence of grade 2 or greater adverse effects of immunotherapy,
- Infection in progress,
- At least one of the 5 hypermetabolic lesions measured on the 18F-FDG PET / CT centrally reviewed in a previously irradiated area,
- Uncontrolled severe comorbidity,
- History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥ 3 years and of low potential risk for recurrence ; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease ; Adequately treated carcinoma in situ without evidence of disease
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 |
|---|---|---|
| SRTPatients with a maximum of 5 residual hypermetabolic lesions observed on 18F- FDG PET / CT after a minimum of 6 months of immunotherapy are treated with SRT, in addition to their anti-PD-1 or anti-PD-L1 immunotherapy as it was administered before randomization in the trial, according to the standards. A maximum of 3 Brain metastases treatable in stereotactic radiotherapy will be included among these hypermetabolic lesions. Each lesion is treated with a total dose of 24 Gy delivered in 3 fractions of 8 Gy (isodose surface). | Radiation | A. (Immunotherapy + SRT) |
| ImmunotherapyPatients with a maximum of 5 residual hypermetabolic lesions observed on 18F- FDG PET / CT after a minimum of 6 months of immunotherapy continue their anti-PD-1 or anti-PD-L1 immunotherapy as it was administered before randomization in the trial, according to the standards. | Drug | A. (Immunotherapy + SRT), B (Immunotherapy alone) |
Primary outcome
The overall survival (OS) benefit of local treatment by stereotactic radiotherapy with immunotherapy versus immunotherapy alone
Time frame: 12 months post-randomization
Overall survival rate, where OS is the time between randomization and death of any cause
6 secondary outcomes
Overall survival (OS)
Time frame: 12 months after randomization of the last patient included
Progression Free Survival (PFS)
Time frame: 12 months after randomization of the last patient included
Quality of life (Qol)
Time frame: 12 months after randomization
Quality of life (Qol)
Time frame: 12 months after randomization
Overall survival (OS) in patients with complete metabolic response rate on 18F- FDG PET / CT 6 months after randomization
Time frame: 6 months after randomization in the SRT arm
Progression Free Survival (PFS) according to complete metabolic response rate on 18F- FDG PET / CT 6 months after randomization
Time frame: 6 months after randomization in the SRT arm
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
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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.
Emilie DEBEAUPUIS contact
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SRT and Immunotherapy in people with Locally Advanced Non Small Cell Lung Cancer and Metastatic Non Small Cell Lung Cancer, run by Institut Cancerologie de l'Ouest at 5 sites in France.
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 11 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sandrine HIRET, MD (+33 (0)2 40 67 99 78, sandrine.hiret@ico.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The overall survival (OS) benefit of local treatment by stereotactic radiotherapy with immunotherapy versus immunotherapy alone (time frame: 12 months post-randomization). 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 21 Feb 2023.