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

NCT03955198

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial Evaluating Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients With NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation
  • Official Title: A Multicentric Phase II Trial of Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients With NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation

Clinical Trial IDs

  • ORG STUDY ID: 18POUM06
  • NCT ID: NCT03955198

Conditions

  • NSCLC

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Patients with NSCLC metachronous oligometastatic diseaseExperimental

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
    
              2. 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
    
              3. 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, and not currently require maintenance
                 doses of > 10 mg prednisone or equivalent per day
    
              4. No history of previous metastatic disease
    
              5. Stage IV metastatic disease
    
              6. 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)
    
              7. All metastatic lesions are less of 4 cm in greater diameter
    
              8. 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)
    
              9. All lesions are amenable to SRT in terms of dose constraints to the organs at risk,
                 with no prior radiotherapy interfering with SRT
    
             10. No local relapse (in-field) or regional mediastinal relapses associated
    
             11. Patient with wild type EGFR and ALK
    
             12. Age ≥ 18 years at time of study entry
    
             13. ECOG performance status < 2 i.e. 0 or 1
    
             14. Body weight >30kg
    
             15. Life expectancy of at least 3 months
    
             16. Adequate Hematology laboratory data within 6 weeks prior to start of treatment:
                 Absolute neutrophils> 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9 g/dL
    
             17. Adequate Biochemistry laboratory data within 6 weeks prior to start of treatment:
                 Total bilirubin ≤ 1.5 x ULN (except patient with confirmed Gilbert's syndrome or liver
                 metastasis: Total bilirubin ≤ 3 X ULN), Transaminases ≤ 2.5 x ULN, Alkalin
                 phosphatases ≤ 5 x ULN, Creatinine clearance > 40 mL/min (Cockcroft)
    
             18. Women should be post-menopaused or willing to accept the use an effective
                 contraceptive regimen during the treatment period and at least 3 months after the end
                 of the study treatment. All non-menopaused women should have a negative pregnancy test
                 within 72 hours prior to registration. Men should accept to use an effective
                 contraception during treatment period and at least 3 months after the end of the study
                 treatment
    
             19. 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
    
             20. Signed written informed consent
    
             21. Patient affiliated to a Social Health Insurance in France
    
            Exclusion Criteria:
    
              1. Cancer histology other than NSCLC
    
              2. Local relapse or mediastinal relapse associated to oligometastatic relapse following
                 chemoradiation
    
              3. Prior radiotherapy near the metastatic lesions precluding ablative SRT
    
              4. 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
    
              5. Metastatic spinal cord compression
    
              6. Brain metastases in the brainstem
    
              7. Known leptomeningeal metastases
    
              8. Patient unable to have MRI for any reason (e.g., due to pacemaker, ferromagnetic
                 implants, claustrophobia, extreme obesity)
    
              9. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
                 exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
                 criteria
    
                   1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after
                      consultation with the Study Physician
    
                   2. Patients with irreversible toxicity not reasonably expected to be exacerbated by
                      treatment with durvalumab may be included only after consultation with the Study
                      Physician
    
             10. Participation in another therapeutic trial within the 30 days prior to entering this
                 study (participation in a survival follow-up period of a clinical study is not an
                 exclusion criterion)
    
             11. 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)
    
             12. Current or prior use of immunosuppressive medication within 14 days before the first
                 fraction of RT (exception: systemic corticosteroids at physiologic doses not exceeding
                 10 mg/day of prednisone or equivalent are allowed as well as steroids as premedication
                 for hypersensitivity reactions (eg, CT scan premedication) - Topical, inhaled, nasal
                 and ophthalmic steroids are not prohibited)
    
             13. 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
    
             14. Known primary immunodeficiency or active HIV (positive HIV 1/2 antibodies)
    
             15. 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)
    
             16. History of active tuberculosis (clinical evaluation that includes clinical history,
                 physical examination and radiographic findings, and TB testing in line with local
                 practice)
    
             17. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
                 infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
                 angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
                 gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
                 situations that would limit compliance with study requirement, substantially increase
                 risk of incurring AEs or compromise the ability of the patient to give written
                 informed consent
    
             18. History of another primary malignancy except for:
    
                   1. Malignancy treated with curative intent and with no known active disease ≥5 years
                      before the first dose of IP and of low potential risk for recurrence
    
                   2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                      of disease
    
                   3. Adequately treated carcinoma in situ without evidence of disease
    
             19. History of severe allergic reactions to any unknown allergens or any components of the
                 study drug
    
             20. History of allogenic organ transplantation
    
             21. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
                 Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
                 30 days after the last dose of IP
    
             22. Female patients who are pregnant or breastfeeding or male or female patients of
                 reproductive potential who are not willing to employ effective birth control from
                 screening to 90 days after the last dose of durvalumab
    
             23. Patient who has forfeited his/her freedom or who is under legal protection
                 (curatorship and guardianship, protection of justice)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression-free survival defined as the time from inclusion to disease progression (per RECIST v1.1) or death from any cause, whichever occurs first.
    Time Frame:24 months for each patient
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Immune progression-free survival defined as the time from inclusion to disease progression (per iRECIST) or death from any cause, whichever occurs first.
    Time Frame:24 months for each patient
    Safety Issue:
    Description:
    Measure:Safety will be assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0).
    Time Frame:24 months for each patient
    Safety Issue:
    Description:
    Measure: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).
    Time Frame:24 months for each patient
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Institut Claudius Regaud

    Trial Keywords

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

    Last Updated

    June 9, 2021