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A Study Evaluating the Efficacy of the Combination of Hypofractionated Stereotactic Radiation Therapy With the Anti-PDL1 Immune Checkpoint Inhibitor Durvalumab in NSCLC Patients With 1 to 4 Brain Metastases (SILK BM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03955198
Recruitment Status : Recruiting
First Posted : May 20, 2019
Last Update Posted : January 6, 2020
Information provided by (Responsible Party):
Institut Claudius Regaud

Brief Summary:

This study is a phase II, multicenter, randomized and comparative study designed to evaluate whether the combination of hypofractionated stereotactic radiation therapy with the anti-PD-L1 Durvalumab in patients with brain metastases from NSCLC (Non-Small-Cell Lung Carcinoma) improves brain tumor control compared to hypofractionated stereotactic radiation therapy alone.

Patients will be assigned in one of the two following arms:

  • Arm A (control arm): radiotherapy alone
  • Arm B (Experimental arm): combined treatment radiotherapy with anti-PD-L1 durvalumab

Total duration of treatment will be 12 months (at maximum in the experimental arm).

Patients will be followed for a maximum of 2 years following the date of randomization.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentric Phase II, Open-label Study Evaluating the Efficacy of the Combination of Hypofractionated Stereotactic Radiation Therapy With the Anti-PDL1 Immune Checkpoint Inhibitor Durvalumab in NSCLC Patients With 1 to 4 Brain Metastases
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Arm A (control arm) Radiation: Radiotherapy
Radiotherapy will be administered alone

Experimental: Arm B (Experimental arm) Combination Product: Radiotherapy + durvalumab
Radiotherapy will be administered in combination with Durvalumab

Primary Outcome Measures :
  1. Time to intra-cranial progression according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria [ Time Frame: 24 months for each patient ]

Secondary Outcome Measures :
  1. Progression-free survival [ 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 ]
  4. 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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
  2. Stage IV metastatic disease with intra-cranial progressive disease documented by MRI evidence
  3. Patient with 1 to 4 brain metastases (< 3.5 cm on T1 post-gadolinium sequence) all amenable to hFSRT, with at least 1 metastasis ≥ 1 cm (RANO-BM criteria evaluation)
  4. Patient with no evidence of extra-cranial progressive disease on 18-FDG PET-CT
  5. Patient with wild type EGFR and ALK
  6. Age ≥ 18 years at time of study entry
  7. ECOG performance status < 2 i.e. 0 or 1
  8. Body weight >30kg
  9. Life expectancy of at least 3 months
  10. Previously treated patients even with immunotherapy are accepted
  11. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 are accepted, if the following conditions are completed:

    • All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study
    • Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.
  12. 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
  13. 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)
  14. 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 nonmenopaused 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
  15. 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
  16. Signed written informed consent
  17. Patient affiliated to a Social Health Insurance in France

Exclusion Criteria:

  1. Central nervous system complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement)
  2. Brain metastases in the brainstem
  3. Known leptomeningeal metastases
  4. All other cancer histology other than NSCLC
  5. Prior history of brain radiotherapy
  6. Patient with associated extra-cranial progressive disease documented by 18-FDG PET-CT
  7. Patient unable to have MRI for any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity)
  8. 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
  9. 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)
  10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  11. 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)
  12. 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
  13. Known primary immunodeficiency or active HIV (positive HIV 1/2 antibodies)
  14. 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)
  15. History of active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice)
  16. 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
  17. 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
  18. History of severe allergic reactions to any unknown allergens or any components of the study drug
  19. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03955198

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Contact: Elizabeth COHEN-JONATHAN MOYAL +33 5 31 15 99 07
Contact: Jonathan KHALIFA +33 5 31 15 54 29

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Centre Hospitalier Universitaire Not yet recruiting
Lyon, France
Contact: Françoise MORNEX    +33 4 78 86 42 53   
Institut Cancerologie de L'Ouest Not yet recruiting
Saint-Herblain, France
Contact: François THILLAYS    +33 240 679 929    franç   
Institut Universitaire du Cancer Toulouse - Oncopole Recruiting
Toulouse, France
Contact: Elizabeth Cohen-Jonathan Moyal    +33 5 31 15 99 07   
Sponsors and Collaborators
Institut Claudius Regaud

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Responsible Party: Institut Claudius Regaud Identifier: NCT03955198    
Other Study ID Numbers: 18POUM06
First Posted: May 20, 2019    Key Record Dates
Last Update Posted: January 6, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut Claudius Regaud:
Brain Metastases
Radiation therapy
Hypo-fractionated stereotactic irradiation
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms by Site
Central Nervous System Neoplasms
Nervous System Neoplasms
Central Nervous System Diseases
Neoplastic Processes
Pathologic Processes
Brain Diseases
Nervous System Diseases
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs