Back to resultsStudy to Assess Neoadjuvant Durvalumab (D) and Platinum-Based Chemotherapy (CT), Followed by Either Surgery and Adjuvant D or CRT and Consolidation D, in Resectable or Borderline Resectable Stage IIB-IIIB NSCLC (MDT-BRIDGE) (MDT-BRIDGE)
Primary Purpose
Non-small Cell Lung Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Durvalumab
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Neoadjuvant, Durvalumab, Chemoradiotherapy, Surgery, Adjuvant, Consolidation, Multidisciplinary team (MDT)
Eligibility Criteria
Inclusion Criteria: Deemed resectable or borderline resectable at baseline, confirmed by MDT evaluation at diagnosis. Previously untreated Stage IIB to select [i.e.N2] Stage IIIB by AJCC v8. Nodal status confirmed with whole body FDG-PET and biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy. Mandatory brain MRI. EGFR and ALK wild-type. Medically operable: adequate cardiac and lung function to undergo resection. Participant must be ≥ 18 years, at the time of screening. Histologically or cytologically documented NSCLC. Minimum life expectancy of 12 weeks. Minimum body weight of 30 kg. Male and female participants must be willing to use acceptable methods of contraception. Female participants of childbearing potential must have negative pregnancy test. Exclusion Criteria: Unresectable NSCLC confirmed by MDT evaluation at baseline Stage IIIC patients Participants whose planned surgery at enrollment is a wedge resection Known EGFR mutation or ALK translocation Participants contraindicated for surgical intervention due to comorbid conditions Participants who are allergic to study intervention. Participants with more than one primary tumour. Known active hepatitis infection, positive HCV antibody, HBsAg or HBV core antibody (anti-HBc), at screening. Female participants who are pregnant or breastfeeding. Judgement by the investigator that the participant should not participate in the study. Previously infected or tested positive for human immunodeficiency virus.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Durvalumab
Arm Description
Durvalumab will be administered to the participants via intravenous infusion (IV)
Outcomes
Primary Outcome Measures
Resection rate
Resection rate is defined as the proportion of all participants who completed all intended neoadjuvant therapy, MDT re-assessment, and definitive surgical resection of the primary tumour.
Secondary Outcome Measures
Resection rate
Resection rate will be further assessed separately in participants deemed resectable at baseline and participants deemed borderline resectable at baseline.
R0, R1, R2 resection rates
The R0, R1, and R2 resection rates are defined as the proportion of resected participants with resection margins assessed as R0, R1, and R2 respectively. R0 corresponds to resection for cure or complete remission, R1 to microscopic residual tumour, R2 to macroscopic residual tumour.
Pathological complete response (pCR)
pCR will be defined as the proportion of participants who undergo surgery and have 0% residual viable tumour cells in resected lung and lymph nodes.
Overall Survival (OS)
OS will be defined as the time from first dose of study intervention until the date of death due to any cause.
Overall Survival (OS) rate
The proportion of participants alive at 12 and 24 months.
Event-free survival (EFS)
EFS is defined as the time from the first dose of study intervention to any of the following events: PD that precludes surgery, progression or recurrence of disease after surgery, PD in the absence of surgery, disease progression, recurrence, or death due to any cause.
Event-free survival (EFS) rate
The proportion of participants alive and event-free at 12 and 24 months.
Progression Free Survival (PFS)
PFS is defined as the time from the first dose of study intervention to RECIST 1.1-defined PD, as assessed by the investigator, or death due to any cause.
Progression Free Survival (PFS) rate
The proportion of participants alive without disease progression at 12 and 24 months.
Objective response rate (ORR) pre-surgery/pre-chemoradiotherapy (CRT)
ORR is defined as the proportion of participants who have complete response or partial response (unconfirmed) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
ORR after definitive CRT
ORR is defined as the proportion of participants who have complete response or partial response (unconfirmed) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Percentage of all participants with circulating tumor DNA (ctDNA) clearance
Circulating tumour DNA clearance (ie, cMR) will be defined as a change from detectable ctDNA to undetectable ctDNA (ctDNA concentration less than limit of detection) at specified timepoints. The percentage of all participants with ctDNA clearance will be assessed.
Number of participants with adverse events
Safety and tolerability will be evaluated in terms of adverse events and serious adverse events.
Surgical safety: Surgical delays
Time from baseline MDT assessment to surgery.
Surgical safety: Duration of surgical procedure
Time from start of surgery to end of surgery.
Surgical safety: Length of hospital stay
Time from the beginning of the surgery/procedure to the discharge of hospital will be assessed.
Surgical safety: Intention of surgical approach
Intention of surgical approach at baseline (minimally invasive vs open thoracotomy).
Surgical safety: Actual surgical procedure
Actual surgical procedure (minimally invasive vs open thoracotomy).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05925530
Brief Title
Study to Assess Neoadjuvant Durvalumab (D) and Platinum-Based Chemotherapy (CT), Followed by Either Surgery and Adjuvant D or CRT and Consolidation D, in Resectable or Borderline Resectable Stage IIB-IIIB NSCLC (MDT-BRIDGE)
Acronym
MDT-BRIDGE
Official Title
A Multicentre, Phase II, Single-Arm, Interventional Study of Neoadjuvant Durvalumab and Platinum-based Chemotherapy (CT), Followed by Either Surgery and Adjuvant Durvalumab or Chemoradiotherapy (CRT) and Consolidation Durvalumab, in Participants With Resectable or Borderline Resectable Stage IIB-IIIB Non-small Cell Lung Cancer (NSCLC)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 16, 2023 (Anticipated)
Primary Completion Date
April 21, 2026 (Anticipated)
Study Completion Date
April 12, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess efficacy and safety of neoadjuvant durvalumab in combination with platinum-based chemotherapy (CT) given as initial therapy after cancer diagnosis followed by either surgery and adjuvant durvalumab or chemoradiotherapy (CRT) and consolidation durvalumab given alone as further therapy in participants with resectable and borderline resectable stage IIB-IIIB NSCLC.
Detailed Description
This will be a multicentre, Phase II, single-arm, global study assessing the efficacy and safety of neoadjuvant durvalumab and platinum-based CT, given intravenously, followed by either surgery and adjuvant durvalumab or definitive CRT and consolidation durvalumab in participants with resectable and borderline resectable stage IIB-IIIB NSCLC.
Neoadjuvant Period A:
All participants will initially receive 2 cycles of neoadjuvant durvalumab + CT (investigator's choice platinum-based) every three weeks. Participants will be assessed for resectability by a multidisciplinary team.
Neoadjuvant Period B:
Cohort 1: Participants who are deemed eligible for surgery will receive study intervention every three weeks for an additional one and up to two cycles, followed by surgery.
CRT:
Cohort 2: Participants with unresectable tumours (according to MDT re-assessment) will receive definitive CRT (6 one-week cycles) for approximately six weeks.
Both cohorts will then go on to receive durvalumab every four weeks until disease progression or recurrence or up to one year.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
Neoadjuvant, Durvalumab, Chemoradiotherapy, Surgery, Adjuvant, Consolidation, Multidisciplinary team (MDT)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
140 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Durvalumab
Arm Type
Experimental
Arm Description
Durvalumab will be administered to the participants via intravenous infusion (IV)
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
MEDI4736
Intervention Description
Participants that go on to receive surgery, will receive durvalumab for up to four cycles prior to surgery. Participants that go on to receive CRT will receive durvalumab for up to two cycles prior to CRT. All participants will receive durvalumab every four weeks until disease progression or recurrence or up to 12 months following surgery/CRT, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.
Primary Outcome Measure Information:
Title
Resection rate
Description
Resection rate is defined as the proportion of all participants who completed all intended neoadjuvant therapy, MDT re-assessment, and definitive surgical resection of the primary tumour.
Time Frame
At day of surgery (Within 40 days of the last dose of neoadjuvant treatment)
Secondary Outcome Measure Information:
Title
Resection rate
Description
Resection rate will be further assessed separately in participants deemed resectable at baseline and participants deemed borderline resectable at baseline.
Time Frame
At the day of surgery (within 40 days after the last dose of neoadjuvant treatment )
Title
R0, R1, R2 resection rates
Description
The R0, R1, and R2 resection rates are defined as the proportion of resected participants with resection margins assessed as R0, R1, and R2 respectively. R0 corresponds to resection for cure or complete remission, R1 to microscopic residual tumour, R2 to macroscopic residual tumour.
Time Frame
At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
Title
Pathological complete response (pCR)
Description
pCR will be defined as the proportion of participants who undergo surgery and have 0% residual viable tumour cells in resected lung and lymph nodes.
Time Frame
At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
Title
Overall Survival (OS)
Description
OS will be defined as the time from first dose of study intervention until the date of death due to any cause.
Time Frame
From first dose of study intervention until death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Title
Overall Survival (OS) rate
Description
The proportion of participants alive at 12 and 24 months.
Time Frame
At 12 months and 24 months
Title
Event-free survival (EFS)
Description
EFS is defined as the time from the first dose of study intervention to any of the following events: PD that precludes surgery, progression or recurrence of disease after surgery, PD in the absence of surgery, disease progression, recurrence, or death due to any cause.
Time Frame
From first dose of study intervention until progression of disease (PD), recurrence or death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Title
Event-free survival (EFS) rate
Description
The proportion of participants alive and event-free at 12 and 24 months.
Time Frame
At 12 months and 24 months
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from the first dose of study intervention to RECIST 1.1-defined PD, as assessed by the investigator, or death due to any cause.
Time Frame
From first dose of study intervention until disease progression, death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Title
Progression Free Survival (PFS) rate
Description
The proportion of participants alive without disease progression at 12 and 24 months.
Time Frame
At 12 months and 24 months
Title
Objective response rate (ORR) pre-surgery/pre-chemoradiotherapy (CRT)
Description
ORR is defined as the proportion of participants who have complete response or partial response (unconfirmed) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time Frame
From first dose of study intervention until death, surgery/start of CRT
Title
ORR after definitive CRT
Description
ORR is defined as the proportion of participants who have complete response or partial response (unconfirmed) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time Frame
From MDT decision timepoint (baseline for this endpoint) until the first tumour assessment after definitive CRT
Title
Percentage of all participants with circulating tumor DNA (ctDNA) clearance
Description
Circulating tumour DNA clearance (ie, cMR) will be defined as a change from detectable ctDNA to undetectable ctDNA (ctDNA concentration less than limit of detection) at specified timepoints. The percentage of all participants with ctDNA clearance will be assessed.
Time Frame
From Cycle 1 Day 1 up to pre-surgery/CRT (within 7 to 14 days pre-surgery/CRT) [Each cycle is of 3 weeks]
Title
Number of participants with adverse events
Description
Safety and tolerability will be evaluated in terms of adverse events and serious adverse events.
Time Frame
From time of signature of the ICF up to at least 90 days after last dose of study intervention
Title
Surgical safety: Surgical delays
Description
Time from baseline MDT assessment to surgery.
Time Frame
Time from baseline MDT assessment to surgery
Title
Surgical safety: Duration of surgical procedure
Description
Time from start of surgery to end of surgery.
Time Frame
Time from start of surgery to end of surgery
Title
Surgical safety: Length of hospital stay
Description
Time from the beginning of the surgery/procedure to the discharge of hospital will be assessed.
Time Frame
Time from the beginning of the surgery/procedure to the discharge of hospital
Title
Surgical safety: Intention of surgical approach
Description
Intention of surgical approach at baseline (minimally invasive vs open thoracotomy).
Time Frame
At baseline
Title
Surgical safety: Actual surgical procedure
Description
Actual surgical procedure (minimally invasive vs open thoracotomy).
Time Frame
At surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Deemed resectable or borderline resectable at baseline, confirmed by MDT evaluation at diagnosis.
Previously untreated Stage IIB to select [i.e.N2] Stage IIIB by AJCC v8.
Nodal status confirmed with whole body FDG-PET and biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy.
Mandatory brain MRI.
EGFR and ALK wild-type.
Medically operable: adequate cardiac and lung function to undergo resection.
Participant must be ≥ 18 years, at the time of screening.
Histologically or cytologically documented NSCLC.
Minimum life expectancy of 12 weeks.
Minimum body weight of 30 kg.
Male and female participants must be willing to use acceptable methods of contraception.
Female participants of childbearing potential must have negative pregnancy test.
Exclusion Criteria:
Unresectable NSCLC confirmed by MDT evaluation at baseline
Stage IIIC patients
Participants whose planned surgery at enrollment is a wedge resection
Known EGFR mutation or ALK translocation
Participants contraindicated for surgical intervention due to comorbid conditions
Participants who are allergic to study intervention.
Participants with more than one primary tumour.
Known active hepatitis infection, positive HCV antibody, HBsAg or HBV core antibody (anti-HBc), at screening.
Female participants who are pregnant or breastfeeding.
Judgement by the investigator that the participant should not participate in the study.
Previously infected or tested positive for human immunodeficiency virus.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies-sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
IPD Sharing URL
https://vivli.org/
Learn more about this trial
Study to Assess Neoadjuvant Durvalumab (D) and Platinum-Based Chemotherapy (CT), Followed by Either Surgery and Adjuvant D or CRT and Consolidation D, in Resectable or Borderline Resectable Stage IIB-IIIB NSCLC (MDT-BRIDGE)
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