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

Non-Small Cell Lung Cancer Clinical Trial

— PACIFIC  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02125461
• Other study ID #: D4191C00001
• Secondary ID: 2014-000336-42
• Status: Completed
• Phase: Phase 3
• Start date: May 7, 2014
• Est. completion date: August 24, 2023

Study information

• Verified date: September 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 713
• Est. completion date: August 24, 2023
• Est. primary completion date: February 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Age at least 18 years.

2. Documented evidence of NSCLC (locally advanced, unresectable, Stage III)

3. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy.

4. World Health Organisation (WHO) Performance Status of 0 to 1.

5. Estimated life expectancy of more than 12 weeks.

Exclusion Criteria:

1. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.

2. Active or prior autoimmune disease or history of immunodeficiency.

3. Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.

4. Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.

5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy.

6. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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).

Locations

Country	Name	City	State
Australia	Research Site	Bedford Park
Australia	Research Site	Bendigo
Australia	Research Site	Box Hill
Australia	Research Site	Clayton
Australia	Research Site	Heidelberg
Australia	Research Site	Herston
Australia	Research Site	Kogarah
Australia	Research Site	Launceston
Australia	Research Site	Nedlands
Australia	Research Site	Port Macquarie
Australia	Research Site	Randwick
Australia	Research Site	Westmead
Australia	Research Site	Woolloongabba
Belgium	Research Site	Aalst
Belgium	Research Site	Gilly
Belgium	Research Site	Leuven
Belgium	Research Site	Libramont-Chevigny
Belgium	Research Site	Liège
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	London	Ontario
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto
Canada	Research Site	Vancouver	British Columbia
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Viña del Mar
France	Research Site	Avignon Cedex 9
France	Research Site	Bayonne
France	Research Site	Brest Cedex
France	Research Site	Lille
France	Research Site	Lyon
France	Research Site	Marseille Cedex 20
France	Research Site	Montpellier Cedex
France	Research Site	Nantes
France	Research Site	Nice
France	Research Site	Pau cedex
France	Research Site	Rennes
France	Research Site	Saint Herblain
France	Research Site	Toulouse
France	Research Site	Villejuif Cedex
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Esslingen
Germany	Research Site	Grosshansdorf
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Löwenstein
Germany	Research Site	Recklinghausen
Germany	Research Site	Regensburg
Germany	Research Site	Villingen-Schwenningen
Greece	Research Site	Athens
Greece	Research Site	Heraklion
Greece	Research Site	Patras
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyula
Hungary	Research Site	Miskolc
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Italy	Research Site	Aviano
Italy	Research Site	Catania
Italy	Research Site	Cremona
Italy	Research Site	Lecce
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Pisa
Italy	Research Site	Roma
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka
Japan	Research Site	Habikino-shi
Japan	Research Site	Hidaka-shi
Japan	Research Site	Hirakata-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kanazawa
Japan	Research Site	Kashiwa
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Kurume-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Natori-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama
Japan	Research Site	Ota-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Takatsuki-shi
Japan	Research Site	Ube-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Hwasun-gun
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Mexico	Research Site	Cuautitlan Izcalli
Mexico	Research Site	Monterrey
Mexico	Research Site	Oaxaca
Mexico	Research Site	Orizaba
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Breda
Netherlands	Research Site	Eindhoven
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Tilburg
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Gdansk
Poland	Research Site	Lublin
Poland	Research Site	Warszawa
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Slovakia	Research Site	Bardejov
Slovakia	Research Site	Kosice
Slovakia	Research Site	Nove Zamky
Slovakia	Research Site	Trnava
South Africa	Research Site	Cape Town
South Africa	Research Site	Pretoria
South Africa	Research Site	Vereeniging
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Gerona
Spain	Research Site	Lérida
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	San Sebastian
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Thailand	Research Site	Bangkok
Thailand	Research Site	Hat Yai
Thailand	Research Site	Muang
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Konya
Turkey	Research Site	Malatya
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Truro
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Blue Ash	Ohio
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Burlington	North Carolina
United States	Research Site	Chandler	Arizona
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Easley	South Carolina
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Gordon	Georgia
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fullerton	California
United States	Research Site	Goodyear	Arizona
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Hazard	Kentucky
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jonesboro	Arkansas
United States	Research Site	Lake Success	New York
United States	Research Site	Lansing	Michigan
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Los Angeles	California
United States	Research Site	Marietta	Georgia
United States	Research Site	Miami Beach	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norwich	Connecticut
United States	Research Site	Orlando	Florida
United States	Research Site	Oxnard	California
United States	Research Site	Pinehurst	North Carolina
United States	Research Site	Port Saint Lucie	Florida
United States	Research Site	Rockville	Maryland
United States	Research Site	Rosedale	Maryland
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Salisbury	Maryland
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Diego	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Spokane	Washington
United States	Research Site	Spokane	Washington
United States	Research Site	Springdale	Arkansas
United States	Research Site	Tampa	Florida
United States	Research Site	Topeka	Kansas
United States	Research Site	Towson	Maryland
United States	Research Site	Tyler	Texas
United States	Research Site	Vancouver	Washington
United States	Research Site	Washington	District of Columbia
United States	Research Site	Waterloo	Iowa
United States	Research Site	Winston-Salem	North Carolina
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	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.	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.
Primary	Overall Survival	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.	From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Secondary	Objective Response Rate (ORR) Based on BICR Assesments According to RECIST 1.1	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.	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.
Secondary	Duration of Response (DoR) Based on BICR Assessments According to RECIST 1.1	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.	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.
Secondary	Proportion of Patients Alive and Progression Free at 12 Months From (APF12) Based on BICR Assessments According to RECIST 1.1	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.	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.
Secondary	Proportion of Patients Alive and Progression Free at 18 Months From (APF18) Based on BICR Assessments According to RECIST 1.1	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.	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.
Secondary	Time to Death or Distant Metastasis (TTDM) Based on BICR Assessments According to RECIST 1.1	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.	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.
Secondary	Percentage of Patients Alive at 24 Months (OS24)	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.	From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Secondary	Time to Second Progression or Death (PFS2)	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.	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.
Secondary	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)	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.	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.
Secondary	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)	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.	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.
Secondary	Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations	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.	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.
Secondary	Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab	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.	Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48. Analysis performed at 22 Mar 2018 DCO.

External Links

•   AstraZeneca Cancer Study Locator Service astrazeneca@emergingmed.com 1-877-400-465
•   CSR redacted synopsis