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Trial record 1 of 7 for:    CASPIAN
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Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN) (CASPIAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03043872
Recruitment Status : Active, not recruiting
First Posted : February 6, 2017
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE January 18, 2017
First Posted Date  ICMJE February 6, 2017
Last Update Posted Date November 16, 2020
Actual Study Start Date  ICMJE March 27, 2017
Actual Primary Completion Date January 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
Overall survival (OS) [ Time Frame: up to 4 years ]
Original Primary Outcome Measures  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Small Cell Lung Carcinoma Extensive Disease
Intervention  ICMJE
  • 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  ICMJE
  • 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 * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 8, 2019)
988
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2017)
795
Estimated Study Completion Date  ICMJE March 31, 2021
Actual Primary Completion Date January 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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  ICMJE NCT03043872
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Haiyi Jiang, M.D. AstraZeneca
PRS Account AstraZeneca
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP