Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT03043872
• Date of registration: 18/01/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN) CASPIAN
• Scientific title: A Phase III, Randomized, Multicenter,Open-Label, Comparative Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for the First-Line Treatment in Patients With Extensive Disease Small-Cell Lung Cancer (SCLC) (CASPIAN)
• Date of first enrolment: March 27, 2017
• Target sample size: 987
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03043872
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, China, Czech Republic, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Slovakia, Spain, Taiwan, Turkey, Ukraine, United States

Contacts

• Name: Haiyi Jiang, M.D.
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:

1. Histologically or cytologically documented extensive disease. Brain metastases; must
be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1
month prior to study treatment.

2. Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment.

3. Life expectancy =12 weeks at Day 1.

4. ECOG 0 or 1 at enrolment.

5. No prior exposure to immune-mediated therapy excluding therapeutic anticancer
vaccines.

Exclusion criteria:

1. Any history of radiotherapy to the chest prior to systemic therapy or planned
consolidation chest radiation therapy (except paliative care outside of the chest).

2. Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical
symptomatology suggesting worsening of PNS

3. Active infection including tuberculosis, HIV, hepatitis B anc C

4. Active or prior documented autoimmune or inflammatory disorders

5. Uncontrolled intercurrent illness, including but not limited to interstitial lung
disease.



Age minimum: 18 Years
Age maximum: 130 Years
Gender: All

Health Condition(s) or Problem(s) studied

Small Cell Lung Carcinoma Extensive Disease

Intervention(s)

Drug: Cisplatin

Drug: Tremelimumab

Drug: Durvalumab

Drug: Carboplatin

Drug: Etoposide

Primary Outcome(s)

Overall Survival (OS) in the Global Cohort; Assessed at Global Cohort Interim Analysis; D + EP Compared With EP [Time Frame: From baseline until death due to any cause. Assessed until global cohort interim analysis DCO (maximum of approximately 23 months).]

OS in the Global Cohort; Assessed at Global Cohort Final Analysis; D + EP Compared With EP and D + T + EP Compared With EP [Time Frame: From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).]

OS in the China Cohort; Assessed at China Cohort First Analysis; D + EP Compared With EP [Time Frame: From baseline until death due to any cause. Assessed until China cohort first analysis DCO (maximum of approximately 19 months).]

OS in the China Cohort; Assessed at China Cohort Second Analysis; D + EP Compared With EP and D + T + EP Compared With EP [Time Frame: From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).]

Secondary Outcome(s)

Change From Baseline in Primary PRO Symptoms as Assessed by EORTC QLQ in the Global Cohort; D + T + EP Compared With EP [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.]

Change From Baseline in Primary Symptoms as Assessed by EORTC QLQ in the China Cohort; D + EP Compared With EP [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.]

Objective Response Rate (ORR) in the Global Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).]

PK of Tremelimumab; Peak and Trough Serum Concentrations in the Global Cohort [Time Frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).]

Percentage of Patients Alive at 18 Months (OS18) in the Global Cohort [Time Frame: At 18 months post-randomization. Assessed at the global cohort final analysis DCO (27 January 2020).]

Time to Deterioration of HRQoL and PRO Symptoms, Assessed Using EORTC QLQ in the China Cohort [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).]

APF6 in the China Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.]

Number of Patients With ADA Response to Tremelimumab in the China Cohort [Time Frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the China cohort second analysis DCO (02 November 2020).]

Number of Patients With ADA Response to Durvalumab in the China Cohort [Time Frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the China cohort second analysis DCO (02 November 2020).]

Change From Baseline in Primary Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the Global Cohort; D + EP Compared With EP [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.]

PFS in the China Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).]

Number of Patients With ADA Response to Tremelimumab in the Global Cohort [Time Frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the global cohort final analysis DCO (27 January 2020).]

OS in the China Cohort; D + T + EP Compared With D + EP [Time Frame: From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).]

Percentage of Patients Alive and Progression Free at 12 Months (APF12) in the Global Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.]

PK of Durvalumab; Peak and Trough Serum Concentrations in the China Cohort [Time Frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).]

Change From Baseline in Primary PRO Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the China Cohort; D + T + EP Compared With EP [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.]

OS in the Global Cohort; D + T + EP Compared With D + EP [Time Frame: From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).]

PK of Tremelimumab; Peak and Trough Serum Concentrations in the China Cohort [Time Frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).]

OS18 in the China Cohort [Time Frame: At 18 months post-randomization. Assessed at the China cohort second analysis DCO (02 November 2020).]

Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations in the Global Cohort [Time Frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).]

Progression-Free Survival (PFS) in the Global Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).]

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13) in the Global Cohort [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).]

Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab in the Global Cohort [Time Frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the global cohort final analysis DCO (27 January 2020).]

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-LC13 in the China Cohort [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).]

Time to Deterioration of Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) in the Global Cohort [Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).]

APF12 in the China Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.]

ORR in the China Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).]

Percentage of Patients Alive and Progression Free at 6 Months (APF6) in the Global Cohort [Time Frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.]

Secondary ID(s)

2016-001203-23

D419QC00001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 04/03/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03043872