Extensive-stage Small-cell Lung Cancer
Conditions
Brief summary
Open-label, single-arm, prospective multicenter phase II clinical trial to determine the efficacy of immunotherapy with durvalumab concomitant with radiochemotherapy, followed by durvalumab maintenance therapy in combination with stereotactic radiotherapy in extensive stage SCLC
Detailed description
This is an open-label, prospective, multi-center single-arm phase II trial. Patients with oligometastatic extensive stage SCLC will be enrolled in the trial. In this trial oligometastatic disease is defined as up to five tumor lesions, whereas the primary tumor including mediastinal lymph node metastases counts as one tumor lesion. The primary tumor including lymph node metastases must be suitable for radiochemotherapy and all distant metastases for stereotactic radiotherapy. Patients must have completed systemic therapy with two cycles of platinum/etoposide/durvalumab and have stable disease or partial response according to RECIST 1.1 criteria. After study inclusion, patients receive radiochemotherapy with concomitant durvalumab (MEDI4736). Concomitant chemotherapy consists of further two cycles platinum/etoposide q3w (summarized cycle 3-4). Dosing of chemotherapy is etoposide 90mg/m² body surface area (BSA) day 1-3 in combination with cisplatin 75mg/m² BSA on day 1 or carboplatin area under the curve (AUC) 5 mg/ml per minute on day 1. Split dose of platinum chemotherapy to 2-3 days is an allowed treatment option. Durvalumab is administered in fixed dose 1500mg in q3w cycles concomitant to chemotherapy and q4w cycles during maintenance treatment. Radiotherapy to the primary tumor including mediastinal lymph node metastases is delivered in single fractions of 1.8Gy once daily up to a cumulative dose of 63.0Gy by intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). In the following, stereotactic radiotherapy is delivered to the up to four further tumor locations during durvalumab maintenance therapy. Sequencing of radiotherapy of the primary tumor and metastases may be changed if radiotherapy of brain, vertebral or other symptomatic metastases is urgently necessary. Stereotactic radiotherapy will be performed according to local standards with established dose and fractionation schemes in ablative doses depending on the affected organ system.
Interventions
RADIATIONThoracic Radiochemotherapy
Radiotherapy to the primary tumor including mediastinal lymph node metastases is delivered in single fractions of 1.8Gy once daily up to a cumulative dose of 63.0Gy by intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT).
DRUGdurvalumab
Durvalumab is administered in fixed dose 1500mg in q3w cycles concomitant to chemotherapy and q4w cycles during maintenance treatment
RADIATIONStereotactic radiotherapy of further tumor locations
Stereotactic radiotherapy is delivered to the up to four further tumor locations during durvalumab maintenance therapy and will be performed according to local standards with established dose and fractionation schemes in ablative doses depending on the affected organ system.
DRUGChemotherapy
Concomitant chemotherapy consists of further two cycles platinum/etoposide q3w (summarized cycle 3-4).
Sponsors
Universität des Saarlandes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For inclusion in the study patients must fulfill all of the following 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 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.
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) rate | 12 month | Efficacy of a treatment scheme consisting of thoracic radiotherapy concomitant to platinum/etoposide/durvalumab therapy followed by stereotactic radiotherapy concomitant to durvalumab maintenance to improve the one year PFS rate using investigator assessments according to RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall survival (OS) | 12 month | One-year OS rate |
Countries
Germany
Contacts
Primary ContactWiebke Pirschel, M.Sc.
Backup ContactMarkus Hecht, Prof.
Outcome results
None listed