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Study of Durvalumab Given With Chemoradiation Therapy in Patients With Unresectable Non-small Cell Lung Cancer

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: NCT03519971
Recruitment Status : Active, not recruiting
First Posted : May 9, 2018
Last Update Posted : July 29, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, international study assessing the efficacy and safety of durvalumab given concurrently with platinum-based CRT (durvalumab + standard of care [SoC] CRT) in patients with locally advanced, unresectable NSCLC (Stage III).

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Durvalumab Other: Placebo Drug: Cisplatin/ Etoposide Drug: Carboplatin/ Paclitaxel Drug: Pemetrexed/ Cisplatin Drug: Pemetrexed/ Carboplatin Radiation: Radiation Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 328 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Given Concurrently With Platinum-based Chemoradiation Therapy in Patients With Locally Advanced, Unresectable NSCLC (Stage III) (PACIFIC2)
Actual Study Start Date : March 29, 2018
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : November 13, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Arm 1: Durvalumab + platinum-based chemotherapy and radiation

Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy.

All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:

  • cisplatin/etoposide
  • carboplatin/paclitaxel
  • pemetrexed/cisplatin
  • pemetrexed/carboplatin

At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.

Drug: Durvalumab
Durvalumab IV (intravenous infusion)
Other Name: MEDI4736

Drug: Cisplatin/ Etoposide
Cisplatin/ Etoposide, as per standard of care

Drug: Carboplatin/ Paclitaxel
Carboplatin /Paclitaxel, as per standard of care

Drug: Pemetrexed/ Cisplatin
Pemetrexed / Cisplatin, as per standard of care

Drug: Pemetrexed/ Carboplatin
Pemetrexed / Carboplatin , as per standard of care

Radiation: Radiation
5 fractions/ week for ~6 weeks (±3 days) (Total 60 Gy)

Placebo Comparator: Arm 2: Placebo + platinum-based chemotherapy and radiation

Placebo in concurrence with platinum-based chemo-radiation therapy.

All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:

  • cisplatin/etoposide
  • carboplatin/paclitaxel
  • pemetrexed/cisplatin
  • pemetrexed/carboplatin

At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.

Other: Placebo
Placebo IV (intravenous infusion)

Drug: Cisplatin/ Etoposide
Cisplatin/ Etoposide, as per standard of care

Drug: Carboplatin/ Paclitaxel
Carboplatin /Paclitaxel, as per standard of care

Drug: Pemetrexed/ Cisplatin
Pemetrexed / Cisplatin, as per standard of care

Drug: Pemetrexed/ Carboplatin
Pemetrexed / Carboplatin , as per standard of care

Radiation: Radiation
5 fractions/ week for ~6 weeks (±3 days) (Total 60 Gy)




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: From date of randomization until the date of objective disease progression or death, assessed up to 4 years. ]

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From the date of randomization until death due to any cause, assessed up to 4 years. ]
  2. Objective Response Rate (ORR) [ Time Frame: From the date of Randomisaton until the date of objective disease progression or death, assessed up to 4 years ]
  3. Overall Survival at 24 months [ Time Frame: From the date of randomization until 24 months ]
  4. Rate of complete response [ Time Frame: From the date of Randomisaton until the date of objective disease progression or death, assessed up to 4 years ]
  5. Duration of response (DoR) [ Time Frame: From the date of first documented response (RECIST 1.1.) until the first date of documented progression or death in the absence of disease progression, assessed up to 4 years. ]
  6. Disease Control Rate (DCR) [ Time Frame: From the date of randomization until 24 weeks. ]
  7. Time from randomization to second progression PFS2 [ Time Frame: From the date of randomization to the earliest progression event subsequent to that used for the PFS endpoint or death, up to 4 years ]
  8. Time to death or distant metastasis (TTDM) [ Time Frame: From the date of randomization to until the first date of distant metastasis or death in the absence of distant metastasis, assessed up to 4 years ]
  9. Presence of ADA for durvalumab in combination with CRT [ Time Frame: From the date of randomization until 6 months after date of last IP dose. ]
  10. To assess symptoms and health-related QoL in patients treated with durvalumab + SoC CRT compared with placebo + SoC CRT using EORTC QLQ-C30 v3 [ Time Frame: From the date of randomisation until PFS2. ]
  11. To assess symptoms and health-related QoL in patients treated with durvalumab + SoC CRT compared with placebo + SoC CRT using QLQ-LC13 [ Time Frame: From the date of randomisation until PFS2. ]
  12. To assess the PK of durvalumab in blood (peak trough concentration) when in combination with CRT [ Time Frame: From the date of randomization until 3 months after date of last IP dose. ]

Other Outcome Measures:
  1. Adverse events [ Time Frame: From the date of randomization until disease progression, assessed up to 4 years. ]


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.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Principal inclusion criteria :

  • Subjects with histologically- or cytologically-documented NSCLC
  • Locally advanced, unresectable (Stage III) NSCLC
  • World Health Organisation (WHO) performance status 0-1
  • At least one measurable lesion, not previously irradiated
  • Must have a life expectancy of at least 12 weeks at randomization

Principal exclusion criteria :

  • Receipt of prior or current cancer treatment, including but not limited to, radiation therapy, investigational agents, chemotherapy, Durvalumab and mAbs.
  • Prior exposure to immune-mediated therapy, including but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti PD L2 antibodies, excluding therapeutic anticancer vaccines.
  • History of allogeneic organ transplantation
  • Active or prior documented autoimmune or inflammatory disorders
  • Uncontrolled intercurrent illness
  • History of another primary malignancy / leptomeningeal carcinomatosis / active primary immunodeficiency
  • Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
  • Mixed small cell and NSCLC histology
  • Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling
  • Known allergy or hypersensitivity to any of the IPs or any of the IP excipients.
  • Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥20 Gy in total (V20) of more than 35% of lung volume.

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): NCT03519971


Locations
Show Show 86 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Jeffrey Bradley, MD AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03519971    
Other Study ID Numbers: D933KC00001
First Posted: May 9, 2018    Key Record Dates
Last Update Posted: July 29, 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AstraZeneca:
Locally Advanced, Unresectable NSCLC, Carcinoma, NSCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Etoposide
Cisplatin
Carboplatin
Pemetrexed
Durvalumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Immunological