A Trial Evaluating Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients With NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation

NCT03955198 | Completed Phase 2

• 1 other identifier: 18POUM06
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 8

Brief Summary

This study is a single-arm phase II, multicenter study designed to evaluate the activity of stereotactic radiotherapy plus the continuation of durvalumab for 12 more months for patients presenting with NSCLC metachronous oligometastatic disease during post-chemoradiotherapy durvalumab consolidation. Fifty patients will have to be enrolled in this phase II trial. Total duration of treatment will be 12 months. Patients will be followed for a maximum of 2 years following the date of inclusion.

Conditions

NSCLC

Keywords

NSCLC; Anti-PD-L1; Durvalumab; Stereotactic Radiation therapy; Oligometastatic disease

Outcome Measures

Primary Outcomes (1)

• Progression-free survival defined as the time from inclusion to disease progression (per RECIST v1.1) or death from any cause, whichever occurs first.

  24 months for each patient

Secondary Outcomes (3)

• Immune progression-free survival defined as the time from inclusion to disease progression (per iRECIST) or death from any cause, whichever occurs first.

  24 months for each patient

• Safety will be assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0).

  24 months for each patient

• Quality of life will be evaluated using the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30).

  24 months for each patient

Study Arms (1)

Patients with NSCLC metachronous oligometastatic disease

EXPERIMENTAL

Combination Product: Radiotherapy + durvalumab

Interventions

Radiotherapy + durvalumab COMBINATION_PRODUCT

Radiotherapy will be administered in combination with Durvalumab

Patients with NSCLC metachronous oligometastatic disease

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
• Under durvalumab consolidation following chemoradiotherapy (sequential or concurrent) for previous stage III NSCLC ; patients must have received at least one infusion of durvaluamb consolidation and should be within 12 months of the first infusion ; the last infusion should have been performed within the last 28 days
• While receiving durvalumab, patients must not have experienced ≥Grade 3 immune related adverse event. Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic. Patients must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE
• No history of previous metastatic disease
• Stage IV metastatic disease
• Patients with 1 to 5 metastases in total, in no more than 3 organs (including brain) documented on the basis of contrast-enhanced CT-scanner of the chest, abdomen and pelvis, 18FDG-PET and brain MRI (and liver MRI in case of liver metastases)
• All metastatic lesions are less of 4 cm in greater diameter
• For patients with brain metastases : surgery of one or several brain lesion(s) is allowed before enrollment provided that there is at least one associated non-resected lesion (cranial or extra-cranial)
• All lesions are amenable to SRT in terms of dose constraints to the organs at risk, with no prior radiotherapy interfering with SRT
• No local relapse (in-field) or regional mediastinal relapses associated
• Patient with wild type EGFR and ALK
• Age ≥ 18 years at time of study entry
• ECOG performance status \< 2 i.e. 0 or 1
• Body weight \>30kg
• Life expectancy of at least 3 months

You may not qualify if:

• Cancer histology other than NSCLC
• Local relapse or mediastinal relapse associated to oligometastatic relapse following chemoradiation
• Prior radiotherapy near the metastatic lesions precluding ablative SRT
• Contraindication to SRT of a lesion due to organ dysfunction; in particular, patients with lung lesions and documented or suspected interstitial lung disease should not be included
• Metastatic spinal cord compression
• Brain metastases in the brainstem
• Known leptomeningeal metastases
• Patient unable to have MRI for any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity)
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician
• Prior therapy with an anti-PD-1, anti-PD-L1 (except during durvalumab consolidation), anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Current or prior use of immunosuppressive medication within 7 days before the first fraction of RT; however the use of corticosteroids at any dose for the management of an AE or a compressive progressive lesion is allowed
• Active suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). Note: participants with vitiligo or alopecia, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, patients with celiac disease controlled by diet alone, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger, are permitted to enroll
• Known primary immunodeficiency or active HIV (positive HIV 1/2 antibodies)
• Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months indicated by positive test for hepatitis B surface antigen (HBV sAG) or hepatitis C virus ribonucleic acid (HCV antibody)

Sponsors & Collaborators

• Institut Claudius Regaud: lead

Study Sites (8)

Institut de Cancérologie de Bourgogne - Auxerre

Auxerre, France

Location

Institut Sainte-Catherine

Avignon, France

Location

Centre François Baclesse

Caen, France

Location

Centre Georges-Francois Leclerc

Dijon, France

Location

Centre Hospitalier Universitaire Lyon Sud

Lyon, France

Location

Centre Henri Becquerel

Rouen, France

Location

CHP Saint Grégoire

Saint-Grégoire, France

Location

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, France

Location

MeSH Terms

Interventions

Radiotherapy; durvalumab

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 20, 2019
• Study Start: May 27, 2021
• Primary Completion: August 26, 2024
• Study Completion: August 26, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

FR (8)