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Submitted by: Trishia Torero 2018-12-03 00:00:00 Last Updated by: Trishia Torero 2021-03-11 09:09:24


A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicenter, Study of Durvalumab as Consolidation Therapy in Patients with Locally Advanced, Unresectable, Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed following Definitive, Platinum-Based, Chemoradiation Therapy

PHRR190110-001991

D933YC00001

2018-CT0463

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicenter, Study of Durvalumab as Consolidation Therapy in Patients with Locally Advanced, Unresectable, Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed following Definitive, Platinum-Based, Chemoradiation Therapy (PACIFIC 5)

This study is a Phase III, randomised, double-blind, placebo-controlled, multicentre study assessing the efficacy and safety of durvalumab compared with placebo as consolidation therapy in patients with locally advanced, unresectable NSCLC (Stage III) who have not progressed following definitive, platinum-based, chemoradiation therapy.

Approximately 360 patients with locally advanced, unresectable NSCLC (Stage III) who received cCRT or sCRT will be randomised globally. These patients will be in complete response (CR), partial response (PR), or have stable disease (SD) following definitive, platinum based, concurrent or sequential chemoradiation therapy.

Regime Classification Priority
2017 - 2022 Global competitiveness and innovation in health Drug discovery and development
Start Date Duration in Months Target Completion Date Actual Completion Date
2018-10-01 72 2024-10-01 0000-00-00

Ongoing

Institution Classification Region LTO #
AstraZeneca Pharmaceuticals (Philippines) Inc. Private Business NCR CDRR-NCR-S-17
Institution Region
AstraZeneca AB Sweden
Name E-Mail Institution and Institution Address
Samia T. Necesito samia.necesito@astrazeneca.com 6th Floor, Inoza Tower, 40th Street, Bonifacio Global City, Taguig, 1634, Philippine
Name E-Mail Institution and Institution Address
Samia T. Necesito samia.necesito@astrazeneca.com 6th Floor, Inoza Tower, 40th Street, Bonifacio Global City, Taguig, 1634, Philippine
Name Expertise Affiliation
Adonis Guancia, MD Oncology Riverside Medical Center
Annielyn Beryl Ong-Cornel, MD Oncology Veterans Memorial Medical Center
Arthur Gregory Lui, MD Oncology Metro Davao Medical and Research Center
Felina Masadao-Adefuin, MD Oncology Baguio General Hospital and Medical Center
Guia Elena Imelda R. Ladrera, MD Oncology Lung Center of the Philippines
Jemela Anne Osorio-Sanchez, MD Oncology Perpetual Succour Hospital
Ma. Luisa Abesamis-Tiambeng, MD Oncology Cardinal Santos Medical Center
Reyna Christy Abas, MD Oncology Cagayan de Oro Medical Center
Project Location Institutional Ethics Review Board
Riverside Medical Center N/A
Veterans Memorial Medical Center Veterans Memorial Medical Center Ethics Review Committee
Metro Davao Medical and Research Center Metro Davao Medical and Research Center – Ethics Review Committee
Baguio General Hospital and Medical Center Baguio General Hospital and Medical Center Ethics Review Committee
Lung Center of the Philippines Lung Center of the Philippines Ethics Review Committee
Perpetual Succour Hospital Perpetual Succour Hospital Institutional Ethics and Review Board
Cardinal Santos Medical Center Cardinal Santos Medical Center Ethics Review Committee
Cagayan de Oro Medical Center Cagayan de Oro Medical Center

Locally Advanced, Unresectable, Non-Small Cell Lung Cancer (Stage III)

PFS using BICR assessments according to RECIST 1.1

OS24

ORR using BICR assessments according to RECIST 1.1

DoR using BICR assessments according to RECIST 1.1

PFS12 and PFS18 using BICR assessments according to RECIST 1.1

PFS2 as defined by local standard clinical practice

TTDM using BICR assessments according to RECIST 1.1

Recruiting

  • China
  • India
  • Mexico
  • Philippines
  • Poland
  • Russia
  • South Korea
  • Taiwan
  • Turkey

Clinical Trial

D933YC00001

20180917133641

2018-11-08

0000-00-00

23

Unspecified

Unspecified

01 Oct 2018

Inclusion Criteria

Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply:

Informed consent

1. Capability to give signed informed consent that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

2. Provision of signed and dated written ICF prior to any mandatory study-specific procedures, sampling, and analyses The ICF process is described in Appendix A 3.

Age

3. Age ≥18 years at the time of Screening Type of patient and disease characteristics

4. Histologically or cytologically documented NSCLC and present with locally

advanced, unresectable (Stage III) disease (according to Version 8 of the (IASLC Staging Manual in Thoracic Oncology]). Positron emission tomography/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis.

5. Receipt of concurrent or sequential chemoradiation therapy, which must be completed within 1 to 28 days prior to first dose of IP in the study.

- For cCRT, patients must have received at least 2 cycles of platinum-based

chemotherapy concurrent with radiation therapy. The last dose of chemotherapy must be prior to, or concurrent with, the final dose of radiation. Consolidation chemotherapy after radiation is not permitted, but no more than 2 cycles of induction chemotherapy prior to cCRT is acceptable.

- For sCRT, patients must have received at least 2 cycles of platinum-based

chemotherapy before radiation therapy. The interval between administration of the last dose of chemotherapy regimen and start of RT must be no more than 6 weeks. Consolidation chemotherapy after radiation is not permitted.

(i) Note: If a patient receives only 1 cycle of platinum-based chemotherapy

concurrent with radiation treatment, this patient will be eligible for the

study to participate in the sCRT stratum.

- The platinum-based chemotherapy regimen must contain cisplatin or carboplatin and 1 of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local SoC regimens. (Gemcitabine is not included.)

- Patients must have received a total dose of radiation of 60 Gy ±10% (54 to 66 Gy) to be randomised as part of the chemoradiation therapy. Study sites are encouraged to adhere to the following mean organ radiation dosing:

(i) Mean lung dose must be

(ii) Mean oesophagus dose must be

(iii) Heart V45 must be <35%, or V30 must be <30%

- Study sites should be aware of the recent RTOG 0617 Trial data demonstrating that doses higher than 60 Gy may be associated with greater toxicity and worse efficacy.

6. No progression following definitive, platinum-based, concurrent or sequential chemoradiation therapy

7. Tumor PD-L1 status, with the Ventana SP263 PD-L1 IHC assay determined by a reference laboratory, must be known prior to randomization. Patient with unknown PD-L1 status is not eligible for the study. “Unknown” refers to (1) insufficient sample which is not able to be analyzed, or (2) sample could be analyzed but results not interpretable.

8. Documented EGFR and ALK status (locally or centrally) at Screening. If the local laboratory will perform the test, a well-validated, local regulatory-approved kit must be used.

- EGFR and ALK status must be available prior to randomisation. After approximately 15% EGFR or ALK mutant patients have been randomised, the incoming patients with EGFR or ALK mutation will not be enrolled.

9. Tumour sample requirements are as follows: Provision of a tumour tissue sample (newly acquired sample <3 months old is preferred, but an archived sample <6 months old is acceptable) in a quantity sufficient to allow for analysis (refer to Section 8.8.1 and the Laboratory Manual for details). Study subject should not have received any intervening systemic therapy other than chemoradiotherapy for Stage III disease as described above.

10. World Health Organization (WHO) PS of 0 or 1 at enrolment

11. No prior exposure to any anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines

12. Adequate organ and marrow function as defined below. Absolute neutrophil count, platelet count, and haemoglobin criteria cannot be met with transfusion or growth factor support administered within 14 days before randomisation.

- Haemoglobin ≥9 g/L

- Absolute neutrophil count >1.5 × 109/L (1500 per mm3)

- Platelet count >100 × 109/L (100000 per mm3)

- Serum bilirubin ≤1.5× the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent

hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who will be allowed in consultation with their primary physician.

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN

- Serum creatinine clearance (CL) >40 mL/min by the Cockcroft-Gault formula

(Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine CL

Males

Creatinine CL = Weight (kg) × (140 - Age)

(mL/min) 72 × serum creatinine (mg/dL)

Females:

Creatinine CL = Weight (kg) × (140 - Age) × 0.85

(mL/min) 72 × serum creatinine (mg/dL)

13. Life expectancy of at least 12 weeks at Day 1

14. WT >30 kg

 

Exclusion Criteria

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

Medical conditions

1. History of allogeneic organ transplantation

2. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).

The following are exceptions to this criterion:

- Patients with vitiligo or alopecia

- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement

- Any chronic skin condition that does not require systemic therapy

- Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician

- Patients with celiac disease controlled by diet alone

3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled

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Interventional

Durvalumab

Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that blocks the interaction of PD-L1 (but not programmed cell death ligand-2) with PD-1 on T cells and CD80 (B7.1) on immune cells. The proposed mechanism of action for durvalumab is interference in the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, including those that may result in tumour elimination. In vitro studies demonstrate that durvalumab antagonises the inhibitory effect of PD-L1 on primary human T cells resulting in the restored proliferation of interferon (IFN)-γ (Stewart et al 2015). In vivo studies have shown that durvalumab inhibits tumour growth in xenograft models via aT-cell-dependent mechanism (Stewart et al 2015). Based on these data, durvalumab is expected to stimulate the patient’s anti-tumour immune response by binding to PD-L1 and shifting the balance towards an anti-tumour response. Durvalumab has been engineered to reduce antibody dependent cellular cytotoxicity and complement-dependent cytotoxicity.

Date Amendment Classification Reason
2021-03-05 Amendments related to the protocol Informed consent

Randomized

Unspecified

Unspecified

Not Applicable

To assess the efficacy of durvalumab treatment compared with placebo in terms of PFS

Phase III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others
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