Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN) (CASPIAN)
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| ClinicalTrials.gov Identifier: NCT03043872 |
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Recruitment Status :
Active, not recruiting
First Posted : February 6, 2017
Last Update Posted : July 15, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Small Cell Lung Carcinoma Extensive Disease | Drug: Durvalumab Drug: Tremelimumab Drug: Carboplatin Drug: Cisplatin Drug: Etoposide | Phase 3 |
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 (Clinical Trial) |
| Actual Enrollment : | 988 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | March 27, 2017 |
| Actual Primary Completion Date : | January 27, 2020 |
| Estimated Study Completion Date : | March 31, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm 1
durvalumab+tremelimumab+EP (carboplatin or cisplatin + etoposide)
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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 |
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Experimental: Arm 2
durvalumab+EP (carboplatin or cisplatin + etoposide)
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Drug: Durvalumab
IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until PD or other discontinuation criteria. 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 |
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Active Comparator: Arm 3
EP (carboplatin or cisplatin + etoposide)
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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 |
- Overall survival (OS) [ Time Frame: up to 4 years ]
- Progression-free survival (PFS) using investigator assessments according to RECIST 1.1 [ Time Frame: up to 2 years ]
- Objective response rate (ORR) using investigator 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 [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 ]
- 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 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- 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.
- Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment.
- Life expectancy ≥12 weeks at Day 1.
- ECOG 0 or 1 at enrolment.
- No prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines.
Exclusion criteria:
- Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest).
- Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS
- Active infection including tuberculosis, HIV, hepatitis B anc C
- Active or prior documented autoimmune or inflammatory disorders
- Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03043872
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| Study Director: | Haiyi Jiang, M.D. | AstraZeneca |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT03043872 |
| Other Study ID Numbers: |
D419QC00001 2016-001203-23 ( EudraCT Number ) |
| First Posted: | February 6, 2017 Key Record Dates |
| Last Update Posted: | July 15, 2020 |
| Last Verified: | July 2020 |
| Individual Participant Data (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 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Carcinoma, Small Cell Lung Oat Cell Carcinoma of Lung Oat Cell Lung Cancer Small Cell Cancer Of The Lung Small Cell Lung Cancer |
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Carcinoma Lung Neoplasms Small Cell Lung Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic |
Bronchial Neoplasms Carboplatin Etoposide Durvalumab Tremelimumab Antineoplastic Agents Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological |