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.

Phase 1

• Conditions: on-small cell lung cancer; MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004490-27-FR
• Lead Sponsor: INSTITUT CLAUDIUS REGAUD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-19
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 100

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.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
12.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)
13.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.
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 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
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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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
a.Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician
b. 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.Current or prior use of chemotherapy, immunotherapy, targeted therapy or hormonal therapy for cancer treatment within 30 days before randomization. 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,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified