Study of durvalumab/placebo + chemoradiation Therapy in Patients with Locally Advanced Non-small Cell Lung Cancer

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2017-004397-34-HU
• Date of registration: 27/03/2018
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Study of durvalumab/placebo + chemoradiation Therapy in Patients with Locally Advanced Non-small Cell Lung Cancer
• Scientific 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) - PACIFIC2
• Date of first enrolment: 23/05/2018
• Target sample size: 390
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004397-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Czech Republic, Hungary, India, Japan, Korea, Republic of, Mexico, Peru, Philippines, Poland, Russian Federation, Thailand, Turkey, Vietnam

Contacts

• Name: Study Information Center
• Affiliation: AstraZeneca AB

• Name: Study Information Center
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
- Subjects with histologically- or cytologically-documented NSCLC
- Locally advanced or 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 234
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 156

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Locally Advanced, Unresectable Non-small Cell Lung Cancer (Stage III)
MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Other descriptive name: DURVALUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Cisplatin
CAS Number: 15663-27-1
Other descriptive name: CISPLATIN

Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Other descriptive name: Carboplatin

Product Name: Pemetrexed
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: PEMETREXED
CAS Number: 137281-23-3
Other descriptive name: PEMETREXED

Product Name: Etoposide
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ETOPOSIDE
CAS Number: 33419-42-0
Other descriptive name: ETOPOSIDE

Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
CAS Number: 33069-62-4
Other descriptive name: Paclitaxel

Primary Outcome(s)

Primary end point(s): PFS using BICR assessments according to RECIST 1.1
ORR using BICR assessments according to RECIST 1.1

Secondary Objective: Assess the efficacy of durvalumab+SoC CRT compared with placebo+SoC CRT in terms of :
-Overall Survival (OS)
-Rate of Complete Response (CR)
-Duration of Response (DoR)
-Disease Control Rate (DCR)
-Time from randomization to second progression (PFS2)
-Time to death or distant metastasis (TTDM)

Pharmacokinetics (PK) of Durvalumab when in combination with CRT.
Immunogenicity of Durvalumab +/- in combination with CRT
Effect of Durvalumab+ SoC CRT compared with placebo on subjects disease-related symptoms and Health related quality of life (HRQoL)
Safety Objective

Main Objective: To assess the efficacy of durvalumab + Standard of care (SoC) chemoradiation therapy (CRT) compared with placebo + SoC CRT in terms of Progression Free Survival (PFS) and objective response rate (ORR)

Timepoint(s) of evaluation of this end point: On-study tumor assessments begin at Baseline, then 16 weeks ±1w after randomization and continue q8w ±1w through 48 weeks (relative to the date of randomization) and then q12w ±1w thereafter (relative to the date of randomization) until RECIST 1.1-defined radiological progression plus an additional regularly scheduled follow-up scan.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Rate of CR, DoR, DCR, and TTDM (BICR RECIST 1.1): Tumor assessments at Baseline, then 16w ±1w, then q8w ±1w through 48w and then q12w ±1w thereafter until PD (+1follow-up scan)
OS, OS24 - Patient level: Assessments every 4w during treatment period and every 8w post IP discontinuation until the end of the study or ICF withdrawn. additional contacted in the week following data cutoff to confirm survival status. ADA will be collected at cycle 1, 2 and 4. ePRO : screening, then on 2, 4, 6, 8, 12, 16, and 20w after first dose of IP, then q8w ±1w through 52 weeks and then q12w ±1w until PD or IP discontinuation, at PD or IP discontinuation, and at 8 and 16 weeks after PD or IP discontinuation

Secondary end point(s): OS and OS24
Rate of CR, DoR, DCR, and TTDM using BICR assessments according to RECIST 1.1
PFS2 as defined by local standard clinical practice
Concentration of durvalumab in blood (such as peak and trough concentration, as data allow; sparse sampling)
ADA (confirmatory results: positive or negative; titers [ADA neutralizing antibodies will also be assessed])
Presence of ADA for durvalumab (confirmatory results: positive or negative; titers)
EORTC QLQ-C30 and QLQ-LC13: Change in symptoms, functioning, and global health status/QoL
Safety assessment

Secondary ID(s)

D933KC00001

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date:
Contact: