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Durvalumab+/- Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (Caspian) (Caspian)

This study is currently recruiting participants.
Verified November 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT03043872
First Posted: February 6, 2017
Last Update Posted: November 16, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
AstraZeneca
  Purpose
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.

Condition Intervention Phase
Small Cell Lung Carcinoma Extensive Disease Drug: Durvalumab Drug: Tremelimumab Drug: Carboplatin Drug: Cisplatin Drug: Etoposide Phase 3

Study Type: Interventional
Study Design: 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 (Stage IV) Small-Cell Lung Cancer (SCLC)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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 ]

Estimated Enrollment: 795
Actual Study Start Date: March 27, 2017
Estimated Study Completion Date: February 28, 2020
Estimated Primary Completion Date: March 29, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
durvalumab+tremelimumab+EP (carboplatin or cisplatin + etoposide)
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
Experimental: Arm 2
durvalumab+EP (carboplatin or cisplatin + etoposide)
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
Active Comparator: Arm 3
EP (carboplatin or cisplatin + etoposide)
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

Detailed Description:

Primary objective of this study is to assess the efficacy of durvalumab + tremelimumab + EP treatment compared with EP in terms of overall survival and progression-free survival.

Appr. 795 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.

  Eligibility

Information from the National Library of Medicine

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, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

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


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 269 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Philip A Dennis, M.D., PhD AstraZeneca
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03043872     History of Changes
Other Study ID Numbers: D419QC00001
2016-001203-23 ( EudraCT Number )
First Submitted: January 18, 2017
First Posted: February 6, 2017
Last Update Posted: November 16, 2017
Last Verified: November 2017

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

Keywords provided by AstraZeneca:
Carcinoma, Small Cell Lung
Oat Cell Carcinoma of Lung
Oat Cell Lung Cancer
Small Cell Cancer Of The Lung
Small Cell Lung Cancer

Additional relevant MeSH terms:
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
Etoposide phosphate
Tremelimumab
Cisplatin
Carboplatin
Etoposide
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs