Description:
This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center,
International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment
for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy
Title
- Brief Title: Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy
- Official Title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)
Clinical Trial IDs
- ORG STUDY ID:
D933QC00001
- NCT ID:
NCT03703297
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Durvalumab | MEDI4736 | Durvalumab + Placebo |
Tremelimumab | | Durvalumab + Tremelimumab |
Purpose
This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center,
International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment
for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy
Trial Arms
Name | Type | Description | Interventions |
---|
Durvalumab + Placebo | Experimental | Durvalumab monotherapy: Durvalumab (1500 mg intravenous [IV]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution. | |
Durvalumab + Tremelimumab | Experimental | Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab. | |
Placebo + Placebo | Placebo Comparator | Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination. | |
Eligibility Criteria
Inclusion criteria:
1. Histologically or cytologically documented limited-stage small cell lung cancer (stage
I-III).
2. Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be
completed within 1 to 42 days prior to randomization and the first dose of IP.
Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total
60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for
hyperfractionated BD schedules.
3. PCI may be delivered at the discretion of investigator and local standard of care, and
must be conducted after the end of cCRT and completed between 1 to 42 days to first
dose of IP.
4 .Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥
12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment.
Exclusion criteria:
1. Extensive-stage SCLC
2. Active or prior documented autoimmune or inflammatory disorders
3. Uncontrolled intercurrent illness, including but not limited to interstitial lung
disease.
4. Active infection including tuberculosis, HIV, hepatitis B and C
5. Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with
chemotherapy)
Maximum Eligible Age: | 130 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free survival (PFS) |
Time Frame: | Approximately 4 years |
Safety Issue: | |
Description: | To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS |
Secondary Outcome Measures
Measure: | Overall Survival (OS) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | To assess the efficacy of Durvalumab & Tremelimumab combination therapy vs Placebo in terms of OS |
Measure: | Objective Response Rate (ORR) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | Progression-free survival PFS |
Time Frame: | Approximately 4 years |
Safety Issue: | |
Description: | To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS |
Measure: | Progression-free survival at 18 months (PFS18) |
Time Frame: | Approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Progression-free survival at 24 months (PFS24) |
Time Frame: | Approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Time to death or distant metastasis (TTDM) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | Proportion of patients alive at 24 months (OS24) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | Proportion of patients alive at and 36 months (OS36) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | Time from randomization to second progression (PFS2) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-C30 v3 |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative) |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Measure: | PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR). |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | To investigate the relationship between PDL1 expression & spatial distribution with Durva (mono) therapy & Durva+Treme (combination) therapy |
Measure: | To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-LC13 |
Time Frame: | Approximately 6 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | AstraZeneca |
Trial Keywords
- Small Cell Lung Cancer
- SCLC
- LS-SCLC
- Limited Stage
- Carcinoma
- Lung Cancer
Last Updated
August 23, 2021