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
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 code: MEDI4736
Conce
Sponsors
AstraZeneca AB
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 ICF and in this protocol. 2. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses. 3. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of sample for optional genetic research that supports Genomic Initiative. 4. Age = 18 years at the time of Screening. 5. Histologically- or cytologically-documented ES-SCLC (stage IV [T any, N any, M1 a/b], or with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan, according to American Joint Committee on Cancer Stage 8th edition). - Brain metastases; must be asymptomatic or treated and stable off steroids and anticonvulsants for at least 1 month prior to study treatment. 6. Patients must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for the ES-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide. 7. WHO/ ECOG Performance Status of 0 to 2 at enrollment. - Note: Patients with PS2 will be limited to a maximum of 30% of the total study population; once this limit is met, additional enrolled patients must have PS 0-1. 8. Baseline computed tomography (CT) / magnetic resonance imaging (MRI) results of the brain, chest and abdomen (including liver and adrenal glands) within 28 days prior to the treatment initiation. 9. No prior exposure to immune-mediated therapy including, but not limited to, other anti- CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines. 10. Adequate organ and marrow function as defined below: - Hemoglobin = 9.0 g/dL. - Absolute neutrophil count = 1.5 × 10^9/L (use of granulocyte colony-stimulating factor is not permitted at screening). - Platelet count = 100 × 10^9/L. - Serum bilirubin = 1.5 × the upper limit of normal (ULN). - In patients without hepatic metastasis: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN. - In patients with hepatic metastases, ALT and AST = 5 × ULN. - Measured or calculated creatinine clearance: > 60 mL/min for patients planned to be treated with etoposide + cisplatin and > 50 mL/min for patients planned to be treated with etoposide + carboplatin as determined by Cockcroft-Gault: - Males: Creatinine CL = (Weight (kg) x (140 - age)) / (72 x serum creatinine (mg/dL)) - Females: Creatinine CL = (Weight (kg) x (140 - age)) / (72 x serum creatinine (mg/dL)) x 0.85 11. Life expectancy = 12 weeks at Day 1. 12. Body weight > 30 kg. 13. Male and/or female 14. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). - Women = 50 years of age wo
Exclusion criteria
Exclusion criteria: 1. History of allogeneic organ transplantation. 2. Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: Patients with vitiligo or alopecia. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. Any chronic skin condition that does not require systemic therapy. Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician. -Patients with celiac disease controlled by diet alone. 3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active 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. 4. 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 IMP 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. 5. History of leptomeningeal carcinomatosis. 6. History of active primary immunodeficiency. 7. Active infection including tuberculosis, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 8. Any unresolved toxicity CTCAE Grade = 2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia and the laboratory values defined in the inclusion criteria: -Patients with Grade = 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. -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. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 10. Received prior systemic therapy for ES-SCLC. -Patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy, or chemoradiotherapy cycle at the time of diagnosis of ES-SCLC. 11. Medical contraindication to platinum (cisplatin or carboplatin)-etoposide-based chemotherapy. 12. Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable. 13. Planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care is allowed but must be completed before first dose of the study medication. 14. Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 90 days after the last dose of IMP. 15. Major surgical procedure within 28 days prior to t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The primary analysis for safety will be conducted approximately 6 months after the last patient is enrolled into the study and the final statistical analysis will be conducted after the last patient had the opportunity to be followed up for a minimum of 12 months or 60% OS maturity, whichever occurs first.;Main Objective: To assess the safety and tolerability profile of durvalumab + EP treatment;Secondary Objective: - To assess the efficacy of durvalumab + EP treatment - To further assess the safety and tolerability profile of durvalumab + EP, including all AEs;Primary end point(s): - Incidence of Grade = 3 AE - Incidence of imAEs | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PFS, ORR, DoR, DoR12, and PFS12 using site Investigator assessments according to RECIST 1.1 - OS and OS12 - Incidence of AEs, SAEs, AESIs, AE resulting in treatment discontinuation, and laboratory findings including clinical chemistry, hematology and urinalysis;Timepoint(s) of evaluation of this end point: The primary analysis for safety will be conducted approximately 6 months after the last patient is enrolled into the study and the final statistical analysis will be conducted after the last patient had the opportunity to be followed up for a minimum of 12 months or 60% OS maturity, whichever occurs first. | — |
Countries
Bulgaria, Canada, Czechia, Czech Republic, Germany, Italy, Turkey
Contacts
Public ContactClinical Study Information Center
AstraZeneca
Outcome results
None listed