Patients with Limited Stage Small-Cell Lung Cancer (LS-SCLC) MedDRA version: 21.1 Level: PT Classification code 10041069 Term: Small cell lung cancer limited stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically or cytologically documented limited-stage SCLC (Stage I-III SCLC [T any, N any, M0] i.e., patients whose disease can be encompassed within a radical radiation portal - Patients with Stage I to IIA disease must be medically inoperable as determined by investigator. - Received an appropriate first line concurrent chemoradiotherapy regimen as defined below, unless after consultation with the global study medical team an alternative is acceptable, received 4 cycles of platinum-based chemotherapy concurrent with RT, which must be completed within 1 to 42 days prior to first dose of IP. The chemotherapy regimen must contain platinum and IV etoposide administered, as per local standard-of-care regimens. The radiotherapy must have commenced no later than the end of Cycle 2 of chemotherapy and patients must have received a total dose of radiation of 60 to 66 Gy over 6 weeks for standard QD radiation schedules or 45 Gy over 3 weeks for hyperfractionated BID radiation schedules. - Patients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based chemotherapy, concurrent with RT. - World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment and randomization. - Mandatory availability of tumor sample, which may include a core needle biopsy, newly cut unstained slides, or fine needle aspirate (FNA) cell block samples. Tissue sample should be submitted before or within 60 days of randomization. However, patients may be enrolled into the study before the pre-treatment tumor tissue sample is submitted. - A newly acquired tumor biopsy (taken following completion of chemoradiotherapy) is optional, provided that a biopsy procedure is technically feasible, and the procedure is not associated with unacceptable clinical risk. - PCI may be delivered at the discretion of investigator and per local standard of care, and completion within 42 days of completion of concurrent CRT. 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 470 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 254
Exclusion criteria
Exclusion criteria: - Extensive-stage SCLC. - Mixed SCLC and NSCLC histology. - Brain metastases or spinal cord compression. All patients will have an MRI (preferred) or CT, preferably with IV contrast of the brain, after completion of first line concurrent chemoradiotherapy and within 1 to 42 days prior to randomization and the first dose of IP. - Patients who received sequential chemoradiation therapy for LS-SCLC (no overlap of RT with chemotherapy). - Receipt of chemotherapy that exceeds 4 cycles in total. Chemotherapy regimens other than etoposide and platinum are not permitted. - Any history of Grade =2 pneumonitis - Active or prior documented autoimmune/inflammatory disorders, uncontrolled intercurrent illness or active infections - Prior exposure to immune-mediated therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS -To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS;Secondary Objective: To Assess : - the efficacy of durvalumab and tremelimumab combination compared to placebo in terms of PFS and OS - the efficacy of durvalumab monotherapy and durvalumab + tremelimumab combination versus placebo in terms of ORR, PFS18, PFS24, TTDM, OS24, OS36 and PFS2 - the efficacy of durvalumab + tremelimumab combination versus durvalumab monotherapy in terms of PFS, ORR and OS - disease-related symptoms and HRQoL in patients treated with durvalumab monotherapy and durvalumab + tremelimumab combination versus placebo using the EORTC QLQ-C30 v3 and QLQ-LC13 - PK of durvalumab monotherapy and durvalumab + tremelimumab combination To Investigate: - the immunogenicity of durvalumab monotherapy and durvalumab + tremelimumab combination - the relationship between PD L1 expression and spatial distribution for durvalumab monotherapy or durvalumab and tremelimumab combination therapy - safety and tolerability of durvalumab monotherapy and durvalumab + tremelimumab combination versus placebo;Primary end point(s): - PFS using BICR assessments according to RECIST 1.1 - OS;Timepoint(s) of evaluation of this end point: - PFS: On-study tumor assessments begin at baseline, then occur q8w ± 1w for the first 72 weeks (relative to the date of randomization), followed by q12w ±1w until up to 96 weeks relative to the date of randomization, and then q24w ±1w thereafter until RECIST 1.1-defined radiological progression, plus one follow-up scan, ad hoc and unscheduled assessments if needed - OS: every 4 weeks during treatment period at least every 8 weeks (±2 weeks) following treatment discontinuation, ad hoc and unscheduled assessments if needed - OS and PFS will be made periodically until end of study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PFS using BICR assessments according to RECIST 1.1 - OS, OS24, OS36 - PFS, ORR, PFS18, PFS24, and TTDM using BICR assessments according to RECIST 1.1, - PFS2 - PFS and ORR using BICR assessments according to RECIST 1.1, OS - EORTC QLQ-C30 and QLQ-LC13: change in symptoms, functioning, and global health status/QoL - Concentration of durvalumab and tremelimumab in serum (such as peak concentration and trough; sparse sampling) - Presence of ADA for durvalumab and tremelimumab (confirmatory results: positive or negative) - PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS, and ORR). - Safety assessment: AEs; laboratory findings including clinical chemistry, hematology, urinalysis; physical examinations; vital signs including blood pressure and pulse; and electrocardiograms;Timepoint(s) of evaluation of this end point: - ORR, PFS18, PFS24, TTDM, PFS. ORR: tumor assessments begin at baseline, then q8w±1w for the first 72 weeks (relative to the date of randomization), followed by q12w±1w until up to 96 weeks , and then q24w±1w thereafter until RECIST 1.1 radiological progression, plus one follow-up scan. - OS: Every 4 weeks during treatment, at least every 8 weeks (±2 weeks) following IP discont. - EORTC QLQ-C30, QLQ-LC13: Every 4 weeks (±3 days) relative to randomization until study termination or death - PK at C1 (postdose) + C2, C5, C26/EoT (predose) and week 12 post IP discont. - ADA at C1, C5, C7, C10, C13, C20 C26/EoT (predose) and week 12 and 24 post IP discont. - Tumor biopsy for PD-L1 is collected at screening period. - Safety: screening and each treatment vist and up to 12 weeks post treatment. | — |
Countries
Argentina, Belgium, Canada, China, Czechia, Czech Republic, Germany, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States, Viet Nam
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed