A Study to Determine Safety of Durvalumab After Sequential Chemo Radiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

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Tracking Information

First Submitted Date ^ICMJE

September 11, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 2, 2018

Actual Study Start Date ^ICMJE

December 31, 2018

Estimated Primary Completion Date

December 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Number of participants with Grade 3 and Grade 4 Treatment-related adverse events (TRAEs)[ Time Frame: From screening (Day -28) till final visit (upto a maximum of 24 months) ]

To assess the safety and tolerability profile of Durvalumab (MEDI4736) as defined by Grade 3 and Grade 4 TRAEs within 6 months from the initiation of durvalumab (MEDI4736) treatment

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Median Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the Investigator[ Time Frame: From the first date of treatment until the date of objective disease progression or death (up to maximum 24 months) ]
To assess the efficacy of Durvalumab (MEDI4736) treatment in terms of PFS. PFS will be calculated using Kaplan-Meier product limit methods.
PFS at 12 months (PFS12)[ Time Frame: From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months) ]
To assess the efficacy of Durvalumab (MEDI4736) treatment in terms of PFS. PFS will be calculated using Kaplan-Meier product limit methods.
PFS at 24 months (PFS24)[ Time Frame: From the first date of treatment until the date of objective disease progression or death (up to maximum 24 months) ]
To assess the efficacy of Durvalumab (MEDI4736) treatment in terms of PFS. PFS will be calculated using Kaplan-Meier product limit methods.
Median overall survival (OS)[ Time Frame: From the first date of treatment until death due to any cause (up to maximum 24 months) ]
To assess the efficacy of Durvalumab(MEDI4736) treatment in terms of OS. OS will be calculated using Kaplan-Meier product limit methods.
OS at 12 months (OS12)[ Time Frame: From the first date of treatment until death due to any cause (up to maximum 12 months) ]
To assess the efficacy of Durvalumab(MEDI4736) treatment in terms of OS. OS will be calculated using Kaplan-Meier product limit methods.
OS at 24 months (OS24)[ Time Frame: From the first date of treatment until death due to any cause (up to maximum 24 months) ]
To assess the efficacy of Durvalumab(MEDI4736) treatment in terms of OS. OS will be calculated using Kaplan-Meier product limit methods.
OS at 36 months (OS36)[ Time Frame: From the first date of treatment until death due to any cause (up to maximum 36 months) ]
To assess the efficacy of Durvalumab(MEDI4736) treatment in terms of OS. OS will be calculated using Kaplan-Meier product limit methods.
Objective Response Rate (ORR) per RECIST 1.1 as assessed by the Investigator[ Time Frame: From 8 weeks ±1 week after investigational product (IP) treatment initiation and continue every 8 weeks (q8w) ±1 week through 52 weeks and every 12 weeks (q12w) ±1 week until disease progression (up to maximum of 24 months) ]
To further assess the efficacy of Durvalumab (MEDI4736) treatment in terms of ORR. ORR (based on Investigator assessment by RECIST 1.1 criteria), together with the corresponding 95% CI, will be reported for participants.
Duration of Response (DOR) per RECIST 1.1 as assessed by the Investigator[ Time Frame: From 8 weeks ±1 week after IP treatment initiation and continue q8w ±1 week through 52 weeks and q12w ±1 week until disease progression (up to maximum of 24 months) ]
To further assess the efficacy of Durvalumab (MEDI4736) treatment in terms of DoR. DoR is defined as the time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression.
Number of participants with lung cancer mortality[ Time Frame: From date of treatment start until death due to lung cancer (up to maximum of 24 months) ]
To assess the efficacy of durvalumab (MEDI4736) treatment in terms of lung cancer mortality.
Number of participants with Adverse events (AEs), Serious adverse events (SAEs), Adverse event of special interests (AESIs), and Immune-mediated adverse event (imAEs)[ Time Frame: From screening (Day -28) till final visit (up to a maximum of 24 months) ]
To further assess the safety and tolerability profile of Durvalumab(MEDI4736) treatment, including all AEs
Number of participants with abnormal physical examinations[ Time Frame: At screening ]
To assess the safety and tolerability profile of Durvalumab (MEDI4736) treatment in terms of the number of participants with abnormal physical examinations. Full physical examinations will include assessments of the head, eyes, ears, nose, and throat and the respiratory, cardiovascular, gastrointestinal (GI), urogenital, musculoskeletal, eurological, rmatological, haematologic/lymphatic, and endocrine systems.
Number of participants with abnormal blood pressure (BP).[ Time Frame: From screening (Day -28) till final visit (up to a maximum of 24 months) ]
To assess the safety and tolerability profile of Durvalumab (MEDI4736) treatment in terms of the number of participants with abnormal BP. BP will be collected before, during, and after IP infusion.
Number of participants with abnormal pulse[ Time Frame: From screening (Day -28) till final visit (up to maximum of 24 months) ]
To assess the safety and tolerability profile of Durvalumab (MEDI4736) treatment in terms of the number of participants with abnormal pulse. Pulse will be collected before, during, and after IP infusion.
Number of participants with abnormal Electrocardiograms (ECGs)[ Time Frame: From screening (Day -28) till final visit (up to a maximum of 24 months) ]
To assess the safety and tolerability profile of Durvalumab (MEDI4736) treatment in terms of the number of participants with abnormal ECGs. Resting 12-lead ECGs will be recorded at screening and as clinically indicated throughout the study. ECGs should be obtained after the participant has been in a supine position for 5 minutes and recorded while the participant remains in that position. In case of clinically significant ECG abnormalities, including a QT interval corrected for heart rate using Fridericia's formula (QTcF) value >470 ms, 2 additional 12-lead ECGs should be obtained over a brief period (eg, 30 minutes) to confirm the finding.
Number of participants with abnormal clinical chemistry[ Time Frame: From screening (Day -28) till final visit (up to a maximum of 24 months) ]
To assess the safety and tolerability profile of Durvalumab (MEDI4736) treatment in terms of the number of participants with abnormal clinical chemistry values. Blood and urine samples for determination of clinical chemistry will be taken at the times indicated in the assessment schedules and as clinically indicated. Abnormal clinically significant laboratory results should be repeated as soon as possible (preferably within 24 to 48 hours). The laboratory variables to be measured are: Albumin, Alkaline phosphatase, Alanine transaminase, Amylase, Aspartate transaminase, Lactate dehydrogenase, Lipase, Magnesium, Potassium, Sodium, Bicarbonate, Calcium, Chloride, Creatinine, Creatinine clearance, Gamma glutamyltransferase, Glucose, Total bilirubin, Total protein, Thyroid-stimulating hormone, T3 and T4 free (reflex), and Urea or blood urea nitrogen, depending on local practice. Other safety assessments to be performed at screening include HbsAg, hepatitis C antibodies, and HIV antibodies.
Number of participants with abnormal haematology[ Time Frame: From screening (Day -28) till final visit (up to a maximum of 24 months)] ]
To assess the safety and tolerability profile of Durvalumab (MEDI4736) treatment in terms of the number of participants with abnormal haematology values. The laboratory variables to be measured are: Absolute neutrophil count, Absolute lymphocyte count, Haemoglobin, Platelet count, Total white cell count, and Coagulation.
Number of participants with abnormal urinalysis.[ Time Frame: From screening (Day -28) till final visit (up to a maximum of 24 months)] ]
To assess the safety and tolerability profile of Durvalumab (MEDI4736) treatment in terms of the number of participants with abnormal urinalysis values. The laboratory variables to be measured are: Bilirubin, Ketones, Blood, pH, Colour and appearance, Protein, Glucose, and Specific gravity. Urinalysis should be done at baseline (screening) and then as clinically indicated.

Descriptive Information

Brief Title ^ICMJE

A Study to Determine Safety of Durvalumab After Sequential Chemo Radiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

Official Title ^ICMJE

A Phase II, Open-Label, Multi-Centre, International Safety Study of Durvalumab Following Sequential Chemotherapy and Radiation Therapy in Patients With Stage III, Unresectable Non-Small Cell Lung Cancer (PACIFIC 6)

Brief Summary

This is a Phase II, open-label, multi-centre study to determine the safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) every 4 weeks [q4w] in participants with unresectable Stage III Non-Small Cell Lung Cancer (NSCLC), who have not progressed following platinum-based sequential chemoradiation therapy (sCRT). This study will be conducted in Europe and North America.

Detailed Description

This is a Phase II, open-label, multi-centre study to determine safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) monotherapy in participants with unresectable Stage III NSCLC who have not progressed following definitive, platinum-based sCRT. Approximately, 150 participants will be treated with the study drug in Europe and North America. Participants will be in complete response (CR), partial response (PR), or have stable disease (SD) following definitive, platinum-based sCRT, as assessed by the Investigator and further supported by the screening imaging radiological assessment. Participants must not have progressed following definitive, platinum-based sCRT; radiation therapy must be completed within 28 days prior to first Investigational product (IP) dose administration. Participants must have histologically- or cytologically-documented NSCLC and locally-advanced, unresectable Stage III disease. Participants will be treated with the study drug in 2 cohorts: approximately 120 participants in the World Health Organization/Eastern Cooperative Oncology Group Performance Status (WHO/ECOG PS) 0 to 1 Cohort and approximately 30 participants in the WHO/ECOG PS 2 Cohort.

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation:
Intervention Model: Single Group Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: Durvalumab
Participants will receive 1500 mg Durvalumab monotherapy via IV infusion q4w for up to a maximum of 24 months with the last administration at Week 104.

Study Arms

Experimental: WHO/ECOG PS 0 to 1 Cohort
120 participants will receive 1500 mg Durvalumab (MEDI4736) monotherapy via IV infusion q4w for up to a maximum of 24 months (up to 26 doses/cycles) with the last administration at Week 104. The study drug should be discontinued prior to 24 months if there is clinical progression or confirmed radiological progression or if there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.
Experimental: WHO/ECOG PS 2 Cohort
30 participants will receive 1500 mg Durvalumab (MEDI4736) monotherapy via IV infusion q4w for up to a maximum of 24 months (up to 26 doses/cycles) with the last administration at Week 104. The study drug should be discontinued prior to 24 months if there is clinical progression or confirmed radiological progression or if there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

150

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

December 30, 2022

Estimated Primary Completion Date

December 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: 1. Capable of giving signed informed consent form (ICF), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses. 3. Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis (optional). 4.18 years or older at the time of signing the ICF. 5. Histologically or cytologically documented NSCLC with locally advanced, unresectable Stage III disease (according to the [International Association for the Study of Lung Cancer] {IASLC} Staging Manual Version 8 [IASLC 2016]). 6. Receipt of sCRT which must have been completed within 28 days prior to first IP dose administration in the study. 7. Participants must not have progressed following platinum-based sCRT, as per Investigator-assessed RECIST 1.1 criteria. 8. Must have a life expectancy of at least 12 weeks at enrolment. 9. WHO/ECOG PS ≤2. 10. Adequate organ and marrow function at enrolment as defined below. These parameters should be achieved without augmentation by growth factors, transfusions, or infusions within 14 days of screening unless required for SoC. 11. Body weight >30 kg at enrolment and first IP dose administration. 12. Male or female. 13. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal participants. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Exclusion Criteria: 1. Participants with locally-advanced NSCLC whose disease has progressed following platinum-based sCRT. 2. Participants who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours. 3. Mixed small-cell lung cancer and NSCLC histology. 4. History of allogeneic organ transplantation. 5. 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]). 6. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, Interstitial lung disease (ILD), serious chronic gastrointestinal (GI) conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent. 7. History of another primary malignancy. 8. History of leptomeningeal carcinomatosis. 9. History of active primary immunodeficiency. 10. Active infection including tuberculosis, hepatitis B (known positive hepatitis B surface antigen [HbsAg] result),hepatitis C virus (HCV), or human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies). Participants with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible. Participants positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). 11. Any unresolved toxicity of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. 12. Known allergy or hypersensitivity to durvalumab (MEDI4736) or any of the IP excipients. 13. Participants who have received cCRT for locally-advanced NSCLC, or who received sCRT with at least 2 concomitant CRT cycles. Prior surgical resection (ie, Stage I or II) is permitted. 14. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. 15. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. 16. 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. 17. Current or prior use of immunosuppressive medication within 14 days before the first dose of IP. 18. Previous IP assignment in the present study. 19. Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study. 20. Participation in another clinical study with an IP during the 4 weeks prior to the first IP dose administration. 21. Prior randomisation or treatment in a previous durvalumab (MEDI4736) ± tremelimumab clinical study regardless of treatment arm assignment. 22. Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of IP. 23. Judgment by the Investigator that the participant is unsuitable to participate in the study and the participant is unlikely to comply with study procedures, restrictions, and requirements. 24. Genetic research study (optional): Exclusion criteria for participation in the optional (DNA) genetic research component of the study include: 1. Previous allogeneic bone marrow transplant. 2. Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample collection.

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

France|United Kingdom|United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

AstraZeneca

Collaborators ^ICMJE

Investigators ^ICMJE

PRS Account

Verification Date

September 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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