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出境医 / 临床实验 / A Trial Evaluating Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients With NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation (SILK BM)

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

Study Description
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.


Condition or disease Intervention/treatment Phase
NSCLC Combination Product: Radiotherapy + durvalumab Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 27, 2021
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025
Arms and Interventions
Arm Intervention/treatment
Experimental: Patients with NSCLC metachronous oligometastatic disease Combination Product: Radiotherapy + durvalumab
Radiotherapy will be administered in combination with Durvalumab

Outcome Measures
Primary Outcome Measures :
  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. [ Time Frame: 24 months for each patient ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Elizabeth COHEN-JONATHAN MOYAL +33 5 31 15 99 07 moyal.elizabeth@iuct-oncopole.fr
Contact: Jonathan KHALIFA +33 5 31 15 54 29 khalifa.jonathan@iuct-oncopole.fr

Locations
Layout table for location information
France
Centre Hospitalier Universitaire Not yet recruiting
Lyon, France
Contact: Françoise MORNEX    +33 4 78 86 42 53    francoise.mornex@chu-lyon.fr   
Institut Cancerologie de L'Ouest Not yet recruiting
Saint-Herblain, France
Contact: François THILLAYS    +33 240 679 929    françois.thillays@ico.unicancer.fr   
Institut Universitaire du Cancer Toulouse - Oncopole Recruiting
Toulouse, France
Contact: Elizabeth Cohen-Jonathan Moyal    +33 5 31 15 99 07    moyal.elizabeth@iuct-oncopole.fr   
Sponsors and Collaborators
Institut Claudius Regaud
Tracking Information
First Submitted Date  ICMJE May 16, 2019
First Posted Date  ICMJE May 20, 2019
Last Update Posted Date June 9, 2021
Actual Study Start Date  ICMJE May 27, 2021
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2021)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2019)
Time to intra-cranial progression according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria [ Time Frame: 24 months for each patient ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2021)
  • 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 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2019)
  • Progression-free survival [ Time Frame: 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) [ Time Frame: 24 months for each patient ]
  • Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) [ Time Frame: 24 months for each patient ]
  • Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Brain Cancer Module [ Time Frame: 24 months for each patient ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial Evaluating Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients With NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation
Official Title  ICMJE A Multicentric Phase II Trial of Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients With NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE NSCLC
Intervention  ICMJE Combination Product: Radiotherapy + durvalumab
Radiotherapy will be administered in combination with Durvalumab
Study Arms  ICMJE Experimental: Patients with NSCLC metachronous oligometastatic disease
Intervention: Combination Product: Radiotherapy + durvalumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 27, 2021)
50
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2019)
100
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Elizabeth COHEN-JONATHAN MOYAL +33 5 31 15 99 07 moyal.elizabeth@iuct-oncopole.fr
Contact: Jonathan KHALIFA +33 5 31 15 54 29 khalifa.jonathan@iuct-oncopole.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03955198
Other Study ID Numbers  ICMJE 18POUM06
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institut Claudius Regaud
Study Sponsor  ICMJE Institut Claudius Regaud
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Institut Claudius Regaud
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP