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

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03519971

Collaborator

(none)

328

Enrollment

Locations

Arms

67.5

Anticipated Duration (Months)

3.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

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 :

Mar 29, 2018

Anticipated Primary Completion Date :

Oct 17, 2022

Anticipated Study Completion Date :

Nov 13, 2023

Arms and Interventions

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 Names: 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)

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 Names:

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)

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [From date of randomization until the date of objective disease progression or death, assessed up to 4 years.]

Secondary Outcome Measures

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

Other Outcome Measures

Adverse events [From the date of randomization until disease progression, assessed up to 4 years.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Barretos	Brazil	14784-400
2	Research Site	Curitiba	Brazil	81520-060
3	Research Site	Florianópolis	Brazil	88034-000
4	Research Site	Fortaleza	Brazil	60336-045
5	Research Site	Porto Alegre	Brazil	90035-003
6	Research Site	Porto Alegre	Brazil	90610-000
7	Research Site	Porto Alegre	Brazil	91350-200
8	Research Site	Ribeirão Preto	Brazil	14021-636
9	Research Site	Ribeirão Preto	Brazil	14048900
10	Research Site	Sao Paulo	Brazil	01246-000
11	Research Site	São José do Rio Preto	Brazil	15090-000
12	Research Site	Brno	Czechia	656 53
13	Research Site	Ostrava	Czechia	703 00
14	Research Site	Praha 2	Czechia	128 08
15	Research Site	Budapest	Hungary	1083
16	Research Site	Budapest	Hungary	1121
17	Research Site	Gyula	Hungary	5700
18	Research Site	Győr	Hungary	9024
19	Research Site	Törökbálint	Hungary	2045
20	Research Site	Bangalore	India	560068
21	Research Site	Chennai	India	600035
22	Research Site	Gurgaon	India	122001
23	Research Site	Karamsad	India	388325
24	Research Site	Mumbai	India	400053
25	Research Site	Nasik	India	422005
26	Research Site	New Delhi	India	110063
27	Research Site	Vadodara	India	390007
28	Research Site	Bunkyo-ku	Japan	113-8603
29	Research Site	Fukuoka-shi	Japan	812-8582
30	Research Site	Koto-ku	Japan	135-8550
31	Research Site	Kyoto	Japan	606-8507
32	Research Site	Nagoya-shi	Japan	464-8681
33	Research Site	Osakasayama	Japan	589-8511
34	Research Site	Sendai-shi	Japan	980-0873
35	Research Site	Yokohama-shi	Japan	241-8515
36	Research Site	Busan	Korea, Republic of	48108
37	Research Site	Chungcheongbuk-do	Korea, Republic of	28644
38	Research Site	Gyeongsangnam-do	Korea, Republic of	52727
39	Research Site	Seoul	Korea, Republic of	03080
40	Research Site	Seoul	Korea, Republic of	05505
41	Research Site	Seoul	Korea, Republic of	135-710
42	Research Site	Aguascalientes	Mexico	20230
43	Research Site	Guadalajara	Mexico	44280
44	Research Site	Mexico City	Mexico	0 3100
45	Research Site	Mérida	Mexico	97134
46	Research Site	México	Mexico	04700
47	Research Site	Orizaba	Mexico	94300
48	Research Site	La Libertad	Peru	13013
49	Research Site	Lima	Peru	15033
50	Research Site	Lima	Peru	L27
51	Research Site	Lima	Peru	LIMA 27
52	Research Site	Lima	Peru	LIMA 34
53	Research Site	Lima	Peru	LIMA 41
54	Research Site	Cebu City	Philippines	6000
55	Research Site	Iloilo City	Philippines	5000
56	Research Site	Iloilo	Philippines	5000
57	Research Site	Makati	Philippines	1229
58	Research Site	Manila	Philippines	1015
59	Research Site	Quezon City	Philippines
60	Research Site	Taguig City	Philippines	1634
61	Research Site	Bydgoszcz	Poland	85-796
62	Research Site	Elbląg	Poland	02-300
63	Research Site	Gdańsk	Poland	80-214
64	Research Site	Olsztyn	Poland	10-228
65	Research Site	Warszawa	Poland	02-781
66	Research Site	Arkhangelsk	Russian Federation	163045
67	Research Site	Chelyabinsk	Russian Federation	454087
68	Research Site	Moscow	Russian Federation	115478
69	Research Site	Moscow	Russian Federation	115533
70	Research Site	Moscow	Russian Federation	125367
71	Research Site	Omsk	Russian Federation	644013
72	Research Site	Rostov-on-Don	Russian Federation	344037
73	Research Site	Saint-Petersburg	Russian Federation	197758
74	Research Site	Bangkok	Thailand	10330
75	Research Site	Bangkok	Thailand	10400
76	Research Site	Hat Yai	Thailand	90110
77	Research Site	Khon Kaen	Thailand	40002
78	Research Site	Mueang	Thailand	50200
79	Research Site	Ankara	Turkey	06230
80	Research Site	Ankara	Turkey
81	Research Site	Antalya	Turkey	07059
82	Research Site	Diyarbakir	Turkey	21280
83	Research Site	Istanbul	Turkey	34030
84	Research Site	Izmir	Turkey	35100
85	Research Site	Hanoi	Vietnam	100000
86	Research Site	Hanoi	Vietnam	10000
87	Research Site	Ho Chi Minh city	Vietnam	700000
88	Research Site	Ho Chi Minh	Vietnam	700000