Patients with Stage I-III Limited Disease Small-Cell Lung Cancer (LD-SCLC) MedDRA version: 20.0 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
Interventions
Product Name: durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: DURVALUMAB
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. - 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 etoposide, 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 for standard QD radiation schedules or 45 Gy for hyperfractionated BID radiation schedules. - Patients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based, concurrent CRT. - World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment and randomization. - Provision of an archived tumour tissue block (or at least 15 newly cut unstained slides, where available) =3 years old, where such samples exist in a quantity sufficient to allow for analysis (refer to the Laboratory Manual for details). - A recent (=3 months) tumour biopsy* (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk. 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 390 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 210
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, prior to study entry. - Patients who received sequential chemoradiation therapy for LD-SCLC (no overlap of RT with chemotherapy). - Receipt of consolidation chemotherapy after radiation. (Treatment with etoposide and platinum after radiation is acceptable as 1 regimen for 1 to 2 cycles; chemotherapy regimens other than etoposide and platinum as consolidation are not permitted.) - Patients with Grade =2 pneumonitis from prior CRT - 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 |
|---|---|
| Primary end point(s): - PFS using BICR assessments according to RECIST 1.1 - OS ; Main Objective: - To assess the efficacy of durvalumab monotherapy as well as durvalumab in combination with tremelimumab therapy compared to placebo in terms of PFS. - To assess the efficacy of durvalumab in combination with tremelimumab therapy compared to placebo in terms of OS. ; Secondary Objective: To Assess : - the efficacy of durvalumab compared to placebo in terms of OS. - the efficacy of durvalumab and durvalumab and tremelimumab compared to placebo in terms of ORR, PFS18a, PFS24a, TTDM, OS24, OS36, and PFS2. - the efficacy of durvalumab and tremelimumab compared to durvalumab in terms of PFS, OS and ORR,, - disease-related symptoms and HRQoL in patients treated with durvalumab or durvalumab and tremelimumab compared to placebo using the EORTC QLQ-C30 v3 and QLQ-LC13. - the PK of durvalumab and durvalumab and tremelimumab. To Investigate: - the immunogenicity of durvalumab and durvalumab and tremelimumab. - the relationship between a patient’s tumor mutational burden (TMB) measured in tumor and/or blood and efficacy outcomes with mono and combination therapy. - safety and tolerability of durvalumab and durvalumab and tremelimumab compared to placebo ; 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 - OS: every 4 weeks during treatment period at least every 8 weeks (±2 weeks) following treat | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 discontinuation - EORTC QLQ-C30, QLQ-LC13: Every 4 weeks (±3 days) relative to randomization until study termination or death - PK at C1 (post dose) and C2, C5, C26 (pre dose) and week 12 post IP discontinuation - ADA at C1, C5, C26 (pre dose) and week 12 and 24 post IP discont - TMB at screening (tumor) and C1, C2, C3, C4, C5 (blood) - Safety: screening and each treatment vist and up to 12 weeks post treatment. ; Secondary end point(s): - OS - ORR, PFS18, PFS24, and TTDM using BICR assessments according to RECIST 1.1, OS24 and OS36, 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) - TMB relative to response/efficacy outcomes (ORR, PFS, and OS) - Safety assessment: AEs; laboratory findings including clinical chemistry, hematology, urinalysis; physical examinations; vital signs including blood pressure and pulse; and electrocardiograms | — |
Countries
Argentina, Belgium, Canada, China, Czech Republic, Germany, India, Italy, Japan, Korea, Republic of, Netherlands, Russian Federation, Spain, Taiwan, Turkey, United States, Vietnam
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed