Patients with oligometastatic extensive stage small cell lung carcinoma (ES-SCLC). In this trial oligometastatic disease is defined as up to five tumor lesions. MedDRA version: 21.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10059514 Term: Small cell lung cancer metastatic System Organ Class: 10029104 - Ne
Conditions
Interventions
Trade Name: IMFIZIN
Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Durvalumab
CAS Number: 1428935-60-7
Current Sponsor
Sponsors
Saarland University represented by the Vice President for Research, Prof. Dr. med. Veit Flockerzi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed first diagnosis of ES-SCLC according to the Veterans Administration Lung Study Group (VALG) Staging System for SCLC1 (disease extension that cannot be treated within one radiation field). 2. Oligometastatic disease defined as follows: • Primary tumor with or without mediastinal or supraclavicular lymph node metastases (counts as one lesion if it can be treated within one radiation field) • Up to four distant tumor lesions/metastases that can be treated with stereotactic radiotherapy (stereotactic radiotherapy of lung metastases in addition to radiochemotherapy of primary tumor should previously be discussed with the principal investigator) • No cytologically confirmed malignant pleural effusion (in case of suspected malignant pleural effusion in imaging, pleurocentesis for cytological assessment is required) 3. Stable disease (SD) or partial response (PR) according to RECIST 1.1 criteria after previous treatment with two cycles of platinum/etoposide/durvalumab. 4. Adequate lung function defined as forced expiratory volume in the first second (FEV1) =1.3 liter in spirometry. 5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent including European Union Data Privacy Directive obtained from the patient prior to performing any protocol-related procedures, including screening evaluations. 6. Age > 18 years at time of study entry. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 . 8. Body weight >30 kg. 9. Adequate normal organ and marrow function as defined below: Hemoglobin =9.0 g/dL White Blood Cells (WBC) = 3,000 per mm3 Platelet count >100,000 per mm3 Serum bilirubin =1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula: Males: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) / 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) x 0.85 / 72 x serum creatinine (mg/dL) 10. 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. 11. Must have a life expectancy of at least 12 weeks. 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 43 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical study with an investigational product during the last 4 weeks 2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 3. Prior systemic anticancer therapy (chemotherapy, immunotherapy, targeted therapy), apart from two cycles of etoposide/platinum + durvalumab. (prior chemotherapy/ immunotherapy/ targeted therapy for other malignancy treated with curative intent =5 years ago is no exclusion criterion). 4. Any unresolved toxicity NCI CTCAE Grade =2 from previous chemoimmunotherapy (2 cycles of platinum/etoposide + durvalumab) with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria 5. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable 6. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 7. 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 8. History of allogenic organ transplantation 9. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g., colitis or Crohn's 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.) 10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active symptomatic infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, QTcF (QT interval on ECG corrected using the Frederica’s formula) >470 ms, 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 11. History of another primary malignancy except for 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 Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease 12. History of leptomeningeal carcinomatosis 13. History of active primary immunodeficiency 14. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 15. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings) 16. Current or prior use of immunosuppressive medication within 14 days before the firs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prove the feasibility of a treatment scheme consisting of thoracic radiotherapy concomitant to platinum/etoposide/durvalumab therapy followed by stereotactic radiotherapy concomitant to durvalumab maintenance. To study the efficacy of this treatment scheme to improve the PFS rate at 12 months. ;Secondary Objective: To study further efficacy endpoints. To study patient reported outcomes (PRO). ;Primary end point(s): For Safety lead-in: Feasibility of the treatment scheme until completion of all planned radiotherapy treatments For Phase II: One-year progression-free survival (PFS) rate using investigator assessments according to RECIST 1.1;Timepoint(s) of evaluation of this end point: End of follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): One-year overall survival (OS) rate PFS (continuous) using investigator assessments according to RECIST 1.1 OS (continuous) Toxicity according to NCI CTCAE v5.0 Local tumor control of irradiated lesions Development of new tumor lesions (outside irradiated area) Patient reported outcomes (PRO): EORTC QLQ-C30, EORTC QLQ-LC13 and EQ-5D-5L;Timepoint(s) of evaluation of this end point: End of follow-up | — |
Countries
Germany
Contacts
Public ContactStudiensekretariat
Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie
Outcome results
None listed