TRAILOCLORI01: 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

Sponsor

Institut Cancerologie de l'Ouest (Other)

Overall Status

Recruiting

CT.gov ID

NCT05111197

Collaborator

(none)

112

Enrollment

Locations

Arms

35.6

Anticipated Duration (Months)

22.4

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Non Small Cell Lung Cancer Metastatic Non Small Cell Lung Cancer	Radiation: SRT Drug: Immunotherapy	Phase 3

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

Study Type:

Interventional

Anticipated Enrollment :

112 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 12, 2022

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A. (Immunotherapy + SRT) Continuation of anti-PD-1 or anti-PD-L1 immunotherapy, started at least 6 months ago, associated with Stereotactic Radiation Therapy (SRT)	Radiation: SRT 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). Drug: Immunotherapy 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.
Active Comparator: B (Immunotherapy alone) Continuation of anti-PD-1 or anti-PD-L1 immunotherapy alone (started at least 6 months ago)	Drug: Immunotherapy 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.

Arm

Intervention/Treatment

Experimental: A. (Immunotherapy + SRT)

Continuation of anti-PD-1 or anti-PD-L1 immunotherapy, started at least 6 months ago, associated with Stereotactic Radiation Therapy (SRT)

Radiation: SRT

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).

Drug: Immunotherapy

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.

Active Comparator: B (Immunotherapy alone)

Continuation of anti-PD-1 or anti-PD-L1 immunotherapy alone (started at least 6 months ago)

Drug: Immunotherapy

Outcome Measures

Primary Outcome Measures

The overall survival (OS) benefit of local treatment by stereotactic radiotherapy with immunotherapy versus immunotherapy alone [12 months post-randomization]
Overall survival rate, where OS is the time between randomization and death of any cause

Secondary Outcome Measures

Overall survival (OS) [12 months after randomization of the last patient included]
Median overall survival at the end of the study
Progression Free Survival (PFS) [12 months after randomization of the last patient included]
Median PFS, time between randomization and progression or death in absence of progression, at the end of the study
Quality of life (Qol) [12 months after randomization]
EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30)
Quality of life (Qol) [12 months after randomization]
Lung cancer-specific Quality of Life Questionnaire EORTC QLQ-LC13
Overall survival (OS) in patients with complete metabolic response rate on 18F- FDG PET / CT 6 months after randomization [6 months after randomization in the SRT arm]
Median overall survival at the end of the study in patients with complete metabolic response rate on 18F- FDG PET / CT (PERSIST)
Progression Free Survival (PFS) according to complete metabolic response rate on 18F- FDG PET / CT 6 months after randomization [6 months after randomization in the SRT arm]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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,
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.

Exclusion Criteria:

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
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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	ICO - Site Paul Papin	Angers	France	49055
2	Chu de Brest	Brest	France	29200
3	Centre François BACLESSE	Caen	France	14000
4	Institut de cancérologie de l'ouest	Saint-Herblain	France	44805
5	Chu de Tours	Tours	France	37044