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

• ClinicalTrials.gov Identifier: NCT03043872
• Recruitment Status: Active, not recruiting
• First Posted: February 6, 2017
• Last Update Posted: January 11, 2021
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: January 18, 2017
• First Posted Date: February 6, 2017
• Last Update Posted Date: January 11, 2021
• Actual Study Start Date: March 27, 2017
• Actual Primary Completion Date: January 27, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 26, 2020): Overall survival (OS) [ Time Frame: up to 4 years ]

Original Primary Outcome Measures (submitted: February 3, 2017)

• Overall survival (OS) [ Time Frame: up to 3 years ]
• Progression-free survival using BICR assessments according to RECIST 1.1 [ Time Frame: up to 2 years ]

Current Secondary Outcome Measures (submitted: November 12, 2020)

• Progression-free survival (PFS) using investigator assessments according to RECIST 1.1 [ Time Frame: up to 4 years ]
• Objective response rate (ORR) using investigator assessments according to RECIST 1.1 [ Time Frame: up to 4 years ]
• Proportion of patients alive and progression free at 6 months from randomization (APF6 [PFS rate at 6 months]) using investigator assessments according to RECIST 1.1 [ Time Frame: up to 6 months ]
• Proportion of patients alive and progression free at 12 months from randomization (APF12 [PFS rate at 12 months]) using investigator assessments according to RECIST 1.1 [ Time Frame: up to 12 months ]
• Proportion of patients alive at 18 months (OS18) [ Time Frame: up to 18 months ]
• Disease-related symptoms measured by EORTC QLQ-C30 [ Time Frame: Up to 2 years ]
• Health-related QoL measured by EORTC QLQ-C30 [ Time Frame: Up to 2 years ]
• Disease-related symptoms measured by EORTC QLQ-LC13 [ Time Frame: Up to 2 years ]
• The immunogenicity of durvalumab and tremelimumab as assessed by frequency of patients with positive ADA titers [ Time Frame: Up to 2 years ]
• The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by peak concentration [ Time Frame: Up to 2 years ]
• The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by trough concentration [ Time Frame: 2 years ]
• Changes in WHO/ECOG performance status [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: February 3, 2017)

• Objective response rate (ORR) using BICR assessments according to RECIST 1.1 [ Time Frame: up to 2 years ]
• Proportion of patients alive and progression free at 6 months from randomization (APF6) using BICR assessments according to RECIST 1.1 [ Time Frame: up to 6 months ]
• Proportion of patients alive and progression free at 12 months from randomization (APF12) using BICR assessments according to RECIST 1.1 [ Time Frame: up to 12 months ]
• Proportion of patients alive at 18 months (OS18) [ Time Frame: up to 18 months ]
• Disease-related symptoms measured by EORTC QLQ-C30 [ Time Frame: Up to 2 years ]
• Health-related QoL measured by EORTC QLQ-C30 [ Time Frame: Up to 2 years ]
• Disease-related symptoms measured by EORTC QLQ-LC13 [ Time Frame: Up to 2 years ]
• The immunogenicity of durvalumab and tremelimumab as assessed by frequency of patients with positive ADA titers [ Time Frame: Up to 2 years ]
• The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by peak concentration [ Time Frame: Up to 2 years ]
• The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by trough concentration [ Time Frame: 2 years ]
• Changes in WHO/ECOG performance status [ Time Frame: 2 years ]

• Current Other Pre-specified Outcome Measures (submitted: October 8, 2018): The safety and tolerability profile of durvalumab ± tremelimumab in combination with EP treatment compared with EP as determined by vital signs, laboratory data, electrocardiograms (ECGs), and physical examnination [ Time Frame: Up to 2 years ]
• Original Other Pre-specified Outcome Measures (submitted: February 3, 2017): The safety and tolerability profile of durvalumab +/- tremelimumab in combination with EP treatment compared with EP as determined by vital signs, laboratory data, electrocardiograms (ECGs), and physical examination [ Time Frame: Up to 2 years ]

Descriptive Information

• Brief Title: Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)
• Official 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)
• Brief Summary: This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of combining durvalumab ± tremelimumab with platinum based chemotherapy (EP) followed by durvalumab ± tremelimumab maintenance therapy versus EP alone as first-line treatment in patients with extensive-stage small-cell lung cancer

Detailed Description

Primary objective of this study is to assess the efficacy of durvalumab + tremelimumab + EP treatment compared with EP and the efficacy of durvalumab + EP treatment compared with EP in terms of OS.

All patients will be randomized in a 1:1:1 ratio in a stratified manner according to the planned platinum-based therapy for Cycle 1 (cisplatin or carboplatin) to receive treatment with durvalumab + tremelimumab + EP (Arm 1), durvalumab + EP (Arm 2), or standard of care- EP (Arm 3). Arm 1 and Arm 2 patients receive the treatment until confirmed disease progression while Arm 3 patients receive up to 6 cycles of EP and prophylactic cranial irradiation if clinically indicated, at the Investigators' discretion.Patients who have discontinued treatment due to toxicity or symptomatic deterioration, clinical progression, or who have commenced subsequent anticancer therapy will be followed up until confirmed disease progression and for survival.

Targeted population are adult patients (aged ≥18 years) with histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC [T any, N any,M1 a/b]), or 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. Patients must have WHO/ECOG performance status of 0 or 1.

Tumor assessments will be performed at Screening as baseline with follow-up at Week 6 ±1 week from the date of randomization, at Week 12 ±1 week from the date of randomization, and then every 8 weeks ±1 week until confirmed objective disease progression.

An independent data monitoring committee (IDMC) comprised of independent experts will be convened to confirm the safety and tolerability of the proposed dose and schedule of durvalumab ± tremelimumab in combination with platinum based chemotherapy at two early stages of enrolment.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Carcinoma Extensive Disease

Intervention

• Drug: Durvalumab
  IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until PD or other discontinuation criteria.
• Drug: Tremelimumab
  IV infusions every 3 weeks for 12 weeks(4 cycles). An additional dose of tremelimumab will be administered in the week 16.
• Drug: Carboplatin
  up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3
• Drug: Cisplatin
  up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3
• Drug: Etoposide
  up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3

Study Arms

• Experimental: Arm 1
  durvalumab+tremelimumab+EP (carboplatin or cisplatin + etoposide)
  Interventions:

  • Drug: Durvalumab
  • Drug: Tremelimumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Etoposide
• Experimental: Arm 2
  durvalumab+EP (carboplatin or cisplatin + etoposide)
  Interventions:

  • Drug: Durvalumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Etoposide
• Active Comparator: Arm 3
  EP (carboplatin or cisplatin + etoposide)
  Interventions:

  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Etoposide

Publications *

• Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. doi: 10.1016/S1470-2045(20)30539-8. Epub 2020 Dec 4.
• Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 8, 2019): 988
• Original Estimated Enrollment (submitted: February 3, 2017): 795
• Estimated Study Completion Date: March 31, 2021
• Actual Primary Completion Date: January 27, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Brazil, Bulgaria, China, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Slovakia, Spain, Taiwan, Turkey, Ukraine, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT03043872
• Other Study ID Numbers: D419QC00001; 2016-001203-23 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

• Study Director: Haiyi Jiang, M.D.; AstraZeneca

• PRS Account: AstraZeneca
• Verification Date: January 2021