Extensive stage small-cell lung cancer 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)
Conditions
Interventions
Sponsors
Norwegian University of Science and Technology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 and any locally required authorization (e.g. Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 2. Age > 18 years at time of study entry. 3. ECOG performance status of 0 or 1. 4. Body weight >30 kg. 5. Adequate normal organ and marrow function as defined below: • Haemoglobin =10.0 g/dL. • Absolute neutrophil count (ANC) =1.5 × 109 /L • Platelet count =100 × 109/L • Serum bilirubin =1.5 x institutional upper limit of normal (ULN). This does 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). • ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5 x ULN. • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. 6. 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. 7. Life expectancy of at least 3 months. 8. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization. 9. At least 1 measurable lesion in the thorax which is possible to irradiate to 30 Gy in 10 fractions. 10. Histologically or cytologically confirmed SCLC. 11. Stage IV disease according to the TNM v8. Patients with stage III disease are eligible if the disease is too widespread to be treated as limited stage SCLC. 12. Pulmonary function: FEV1 >1 L or >30 % of predicted value and DLCO >30 % of predicted value. 13. Female patients of childbearing potential (postmenarcheal, not postmenopausal [>12 continuous months of amenorrhea with no identified cause other than menopause], and no surgical sterilization) should use highly effective contraception and take active measures to avoid pregnancy while undergoing systemic study therapy and for at least 5 months after the last dose. 14. Patients with brain metastases are eligible provided they are asymptomatic or treated and stable on steroids and/or anticonvulsants prior to the start of treatment. 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 182 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 112
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical study with an investigational product during the last 30 days. 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. Previous chemo- or radiotherapy for SCLC. Patients who have undergone surgery, but no adjuvant therapy are eligible. 4. 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. 5. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Chief Investigator. 6. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Chief Investigator. 7. Any concurrent chemotherapy, investigational product or biologic cancer therapy. 8. Any prior checkpoint inhibitor therapy, including durvalumab. 9. 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 drugs. 10. Major surgical procedure within 28 days prior to the first dose of study drugs. Note: Local surgery of isolated lesions for palliative intent is acceptable. 11. History of allogenic organ transplantation. 12. 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]). The following are exceptions to this criterion: a. Patients with vitiligo or alopecia. b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. c. Any chronic skin condition that does not require systemic therapy. d. Patients without active disease in the last 5 years may be included but only after consultation with the Chief Investigator. e. Patients with celiac disease controlled by diet alone. 13. 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. 14. History of another primary malignancy except for: a. 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. b. Localized breast or prostate cancer treated with hormonal therapy alone. c. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. d. Adequately treated carcinoma in situ without evidence of disease. 15. Leptomeningeal carcinomatosis. 16. Untreated, symptomatic central nervous system (CNS) metastases. Any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on steroids and/or anticonvulsants prio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether adding thoracic radiotherapy to durvalumab plus chemotherapy improves survival. ;Secondary Objective: - To investigate whether adding thoracic radiotherapy improves overall response rates, response rates in non-irradiated lesions and PFS. - To investigate whether thoracic radiotherapy improves local control. - To compare the frequency and severity of adverse events between the treatment arms. - To compare the duration of severe adverse events between the treatment arms. - To compare the frequency and timing of brain metastases between treatment arms. - To compare cognitive function between patients who receive PCI and those who do not. - To investigate associations between outcomes of study treatment and biomarkers in tissue, blood and stool (e.g. ctDNA in blood, miRNA, gut microbiome). ;Primary end point(s): 1-year overall survival;Timepoint(s) of evaluation of this end point: Primary survival analysis will be performed 14 months after last patient entry | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 2-year, 3-year, 4-year and 5-year overall survival. Overall response rates. Response rate in non-irradiated lesions. Overall progression-free survival. Progression free survival in non-irradiated lesions. Local control rates in the thorax. Frequency and severity of adverse events. Duration of severe adverse events. Frequency and timing of brain metastases. Cognitive function in patients who receive PCI and those who do not. Associations between outcomes of study treatment and biomarkers in tissue, blood and stool (e.g. ctDNA in blood, miRNA and gut microbiome).;Timepoint(s) of evaluation of this end point: Analyses will be performed until 5 years after last patient entry. | — |
Countries
Estonia, Netherlands, Norway
Contacts
Public ContactBjørn Henning Grønberg
Norwegian University of Science and Technology
Outcome results
None listed