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

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ClinicalTrials.gov Identifier: NCT03519971
Recruitment Status : Recruiting
First Posted : May 9, 2018
Last Update Posted : June 3, 2019
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)
Estimated Enrollment : 300 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 Non-small Cell Lung Cancer (Stage III) (PACIFIC2)
Actual Study Start Date : March 29, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : August 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
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. ]
  2. Objective response rate (ORR) [ 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. To assess the PK of durvalumab in blood (trough concentration) when in combination with CRT [ Time Frame: From the date of randomization until 3 months after date of last IP dose. ]
  3. 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. ]
  4. 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 time of signature of informed consent until 16 weeks after progression or IP discontinuation. ]
  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. Time from randomization to second progression PFS2 [ Time Frame: from dose discontinuation until assessed up to 4 years ]
  7. Time to death or distant metastasis (TTDM) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years ]
  8. Rate of complete response [ Time Frame: Obtained up until progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years ]
  9. 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 time of signature of informed consent until PFS2. ]
  10. 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

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Ages Eligible for Study:   18 Years and older   (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


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study, Local service 1-877-400-4656 AstraZeneca@emergingmed.com

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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     History of Changes
Other Study ID Numbers: D933KC00001
First Posted: May 9, 2018    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019

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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 Non-small Cell Lung Cancer, NSCLC, Carcinoma, Non-Small-Cell Lung Cancer

Additional relevant MeSH terms:
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Durvalumab
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
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Etoposide phosphate
Pemetrexed
Antibodies, Monoclonal
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