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

NCT05111197 | Unknown Phase 3

• 1 other identifier: ICO-2021-08
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 5

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.

Conditions

Locally Advanced Non Small Cell Lung Cancer; Metastatic Non Small Cell Lung Cancer

Keywords

lung; Immunotherapy; Stereotactic radiotherapy; 18F- FDG PET/ CT; Locally advanced cancer; Metastatic cancer; Overall survival; Progression Free Survival

Outcome Measures

Primary Outcomes (1)

• 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

  12 months post-randomization

Secondary Outcomes (6)

• Overall survival (OS)

  12 months after randomization of the last patient included

• Progression Free Survival (PFS)

  12 months after randomization of the last patient included

• Quality of life (Qol)

  12 months after randomization

• Quality of life (Qol)

  12 months after randomization

• 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

Study Arms (2)

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)

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)

Drug: Immunotherapy

Interventions

SRT RADIATION

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).

A. (Immunotherapy + SRT)

Immunotherapy DRUG

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.

A. (Immunotherapy + SRT); B (Immunotherapy alone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (5)

ICO - Site Paul Papin

Angers, 49055, France

RECRUITING

Chu de Brest

Brest, 29200, France

NOT YET RECRUITING

Centre François BACLESSE

Caen, 14000, France

NOT YET RECRUITING

Institut de cancérologie de l'ouest

Saint-Herblain, 44805, France

RECRUITING

Chu de Tours

Tours, 37044, France

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Central Study Contacts

Sandrine HIRET, MD

CONTACT

+33 (0)2 40 67 99 78; sandrine.hiret@ico.unicancer.fr

Emilie DEBEAUPUIS

CONTACT

emilie.debeaupuis@ico.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 8, 2021
• Study Start: January 12, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: February 21, 2023

Record last verified: 2022-02

Locations

FR (5)