Clinical trial NCT03519971: Study of Durvalumab Given With Chemoradiation Therapy in Patients With Unresectable Non-small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Locally Advanced, Unresectable NSCLC, Carcinoma, NSCLC
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-05-09
Enrollment: 328
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
measure: Overall Survival (OS)
timeFrame: From screening until confirmed PD, assessed up to the DCO date (a maximum of approximately 1988 days).
measure: Percentage of Participants Alive at 24 Months From Randomization (OS24)
timeFrame: Month 24
measure: Complete Response Rate (CRR)
timeFrame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
measure: Duration of Response (DoR)
timeFrame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
measure: Disease Control Rate (DCR)
timeFrame: Week 24
measure: Time to Death or Distant Metastasis (TTDM)
timeFrame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
measure: Time From Randomization to Second Progression (PFS2)
timeFrame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
measure: Serum Concentration of Durvalumab
timeFrame: End of infusion on Week 0, pre-infusion on Weeks 4 and 12, and Month 3 follow-up
measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
timeFrame: Pre-dose on Day 1 of Cycles 1, 2 and 4
measure: Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Average Over 12 Months
timeFrame: At screening, 2, 4, 6, 8, 12, 16, and 20 weeks after randomization, then every 8 weeks ±1 week up to 52 weeks, and then every 12 weeks ±1 week thereafter until PFS2. Assessed up to 12 months.
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From time of signature of informed consent up to 90 days after last dose of study treatment or up to the date of initiation of the first subsequent therapy, whichever occurs first, approximately 1988 days.
Other outcomes:
Locations:
city: Barretos
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Florianópolis
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Chennai
country: India
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Karamsad
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: Nasik
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Vadodara
country: India
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kyoto
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Chungcheongbuk-do
country: Korea, Republic of
facility: Research Site
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Aguascalientes
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Mérida
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: Orizaba
country: Mexico
facility: Research Site
city: La Libertad
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Cebu City
country: Philippines
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Iloilo
country: Philippines
facility: Research Site
city: Makati
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Taguig City
country: Philippines
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Elbląg
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Mueang
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Diyarbakir
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Jeffrey Bradley, MD
role: PRINCIPAL_INVESTIGATOR
References: