A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC)

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ClinicalTrials.gov Identifier: NCT02125461

Recruitment Status : Completed

First Posted : April 29, 2014

Results First Posted : January 30, 2019

Last Update Posted : October 10, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

April 25, 2014

First Posted Date ^ICMJE

April 29, 2014

Results First Submitted Date ^ICMJE

February 13, 2018

Results First Posted Date ^ICMJE

January 30, 2019

Last Update Posted Date

October 10, 2023

Actual Study Start Date ^ICMJE

May 7, 2014

Actual Primary Completion Date

February 13, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Progression Free Survival Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years. ]
PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS was calculated using the Kaplan-Meier technique.
Overall Survival [ Time Frame: From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using the Kaplan-Meier technique.

Original Primary Outcome Measures ^ICMJE

Overall Survival (OS) [ Time Frame: Estimated to be from baseline up to 5 years ]
Overall Survival is defined as the time from the date of randomization until death due to any cause.
Progression Free Survival (PFS) using investigational site assessments according to RECIST 1.1 [ Time Frame: Estimated to be from baseline up to 5 years ]
Progression-Free Survival is defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression).

Change History

Current Secondary Outcome Measures ^ICMJE

Objective Response Rate (ORR) Based on BICR Assesments According to RECIST 1.1 [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
ORR was defined as the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
Duration of Response (DoR) Based on BICR Assessments According to RECIST 1.1 [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
DoR was defined as the time from date for first documented response of CR or PR until the first documented response of progression per RECIST 1.1 or death in the absence of progression. DoR was calculated using the Kaplan-Meier technique.
Proportion of Patients Alive and Progression Free at 12 Months From (APF12) Based on BICR Assessments According to RECIST 1.1 [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years. ]
APF12 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months.
Proportion of Patients Alive and Progression Free at 18 Months From (APF18) Based on BICR Assessments According to RECIST 1.1 [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years. ]
APF18 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 18 months after randomization per the Kaplan-Meier estimate of PFS at 18 months.
Time to Death or Distant Metastasis (TTDM) Based on BICR Assessments According to RECIST 1.1 [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
TTDM was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that was outside of the radiation field according to RECIST 1.1 or proven by biopsy. TTDM was calculated using the Kaplan-Meier technique.
Percentage of Patients Alive at 24 Months (OS24) [ Time Frame: From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
OS24 was defined as the percentage of patients who were alive at 24 months after randomization per the Kaplan-Meier estimate of OS at 24 months.
Time to Second Progression or Death (PFS2) [ Time Frame: Following confirmed progression, patients were assessed every ~12 weeks until second disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
PFS2 was defined as the time from randomization to the time of the second progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could have involved any of the following: objective radiological, symptomatic progression, or death. RECIST assessments were not collected for assessment of PFS2. PFS2 was calculated using the Kaplan-Meier technique.
Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL), Assessed Using European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
Global health status/HRQoL was assessed using the EORTC QLQ-C30 global QoL scale which includes 2 items from the QLQ-C30: "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall QoL during the past week?" (Item 30). Scores from 0 to 100 were derived for each item with higher scores indicating a better health status. Time to deterioration for global health status/HRQoL was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in global health status/HRQoL from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful deterioration. Time to deterioration was calculated using the Kaplan-Meier technique.
Time to Deterioration of Primary Patient-Reported Outcome (PRO) Symptoms, Assessed Using European Organization for Research and Treatment of Cancer QoL Lung Cancer Module (EORTC QLQ-LC13) [ Time Frame: At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years. ]
The EORTC QLQ-LC13 is a lung cancer specific module from the EORTC comprising 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, chest pain, arm/shoulder pain, and other pain), treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. Scores from 0 to 100 were derived for each symptom item with higher scores representing greater symptom severity. Time to symptom deterioration was defined as time from randomization until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration. Results are presented for time to deterioration in the following PRO endpoints identified as primary for EORTC QLQ-LC13: dyspnea, cough, hemoptysis and chest pain. Time to deterioration was calculated using the Kaplan-Meier technique.
Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations [ Time Frame: Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48, and post-dose on Day 1 (Week 0) and Week 24. Analysis performed at 22 Mar 2018 DCO. ]
To evaluate PK, blood samples were collected pre-dose and post-dose and trough and peak serum concentrations of durvalumab, respectively, were determined. Pre-dose samples were taken within 60 minutes before infusion and post-dose samples were taken within 10 minutes after the end of infusion.
Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab [ Time Frame: Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48. Analysis performed at 22 Mar 2018 DCO. ]
ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted by ≥4-fold following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Confirmed ADA positive samples were subsequently tested in a neutralizing antibody assay.

Original Secondary Outcome Measures ^ICMJE

Overall Survival at 24 months (OS24) [ Time Frame: Estimated to be from baseline up to 5 years ]
OS24 is defined as the number (%) of patients who are alive at 24 months after randomization per the Kaplan-Meier estimate of overall survival at 24 months.
Duration of Response (DoR) using investigational site assessments according to RECIST 1.1 [ Time Frame: Estimated to be up to 3 years ]
DoR is defined as the time from date for first documented response of Complete Response (CR) or Partial Response (PR) until the first documented response of progression per RECIST 1.1 or death in the absence of progression.
Objective Response Rate (ORR) using investigational site assessments according to RECIST 1.1 [ Time Frame: Estimated to be up to 3 years ]
ORR is defined as the number (%) of patients with at least one visit response of Complete Response (CR) or partial response (PR) per RECIST 1.1.
Proportion of patients alive and progression free at 12 months from (APF12) using investigational site assessments according to RECIST 1.1 [ Time Frame: Estimated to be up to 3 years ]
APF12 is defined as the number (%) of patietns who are alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of progression free survival at 12 months.
Proportion of patients alive and progression free at 18 months from(APF18) using investigational site assessments according to RECIST 1.1 [ Time Frame: Estimated to be up to 3 years ]
APF18 is defined as the number (%) of patients who are alive and progression free per RECIST 1.1 at 18 months after randomization per the Kaplan-Meier estimate of progression free survival at 18 months.

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

Official Title ^ICMJE

A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients With Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC)

Brief Summary

A Global Study to Assess the Effects of MEDI4736 following concurrent chemoradiation in Patients with Stage III Unresectable Non-Small Cell Lung Cancer.

Detailed Description

A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC)

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Non-Small Cell Lung Cancer

Intervention ^ICMJE

Drug: MEDI4736
MEDI4736 by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier . The 2:1 ratio (MEDI4736 to placebo).
Other: PLACEBO
PLACEBO by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier . The 2:1 ratio (MEDI4736 to placebo).

Study Arms ^ICMJE

Experimental: MEDI4736
MEDI4736 (intravenous infusion)

Intervention: Drug: MEDI4736
Placebo Comparator: PLACEBO
Placebo (matching placebo for intravenous infusion)

Intervention: Other: PLACEBO

Publications *

* 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

Completed

Actual Enrollment ^ICMJE

713

Original Estimated Enrollment ^ICMJE

880

Actual Study Completion Date ^ICMJE

August 24, 2023

Actual Primary Completion Date

February 13, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Age at least 18 years.
Documented evidence of NSCLC (locally advanced, unresectable, Stage III)
Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy.
World Health Organisation (WHO) Performance Status of 0 to 1.
Estimated life expectancy of more than 12 weeks.

Exclusion Criteria:

Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
Active or prior autoimmune disease or history of immunodeficiency.
Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy.
Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 130 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Australia, Belgium, Canada, Chile, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Singapore, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam

Removed Location Countries

Argentina, Brazil, Philippines, Russian Federation

Administrative Information

NCT Number ^ICMJE

NCT02125461

Other Study ID Numbers ^ICMJE

D4191C00001
2014-000336-42 ( 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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 deidentified 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

Current Responsible Party

AstraZeneca

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

AstraZeneca

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Phil Dennis, MD

AstraZeneca

PRS Account

AstraZeneca

Verification Date

September 2023

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

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