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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06284317




Registration number
NCT06284317
Ethics application status
Date submitted
1/04/2024
Date registered
21/02/2024
Date last updated
4/04/2024

Titles & IDs
Public title
A Study to Evaluate the Benefit of Adding Durvalumab After Chemotherapy, Durvalumab and Surgery in Patients With Early-stage, Operable, Non-small Cell Lung Cancer.
Scientific title
An International, Multicentre, Open-label Randomised Phase III Trial to Evaluate the Benefit of Adding Adjuvant Durvalumab After Neoadjuvant Chemotherapy Plus Durvalumab in Patients With Stage IIB-IIIB (N2) Resectable NSCLC
Secondary ID [1] 0 0
ETOP 25-23
Universal Trial Number (UTN)
Trial acronym
ADOPT-lung
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Adjuvant durvalumab

Experimental: Durvalumab - Protocol treatment in the adjuvant phase consists of adjuvant durvalumab

No Intervention: Observation - Observation only


Treatment: Drugs: Adjuvant durvalumab
Durvalumab is given at a fixed dose of 1500 mg i.v. every 4 weeks (±1 week) until relapse
or unacceptable toxicity, for a maximum of 12 cycles after surgery.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease-free survival (DFS)
Timepoint [1] 0 0
From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)
Secondary outcome [1] 0 0
Response rate as per investigator assessment.
Timepoint [1] 0 0
From the date of enrolment until randomisation (approximately 24 weeks after enrolment)
Secondary outcome [2] 0 0
Proportion of patients undergoing surgery
Timepoint [2] 0 0
From the date of enrolment until randomisation (approximately 24 weeks after enrolment)
Secondary outcome [3] 0 0
Proportion of patients with surgical outcome R0 and R1
Timepoint [3] 0 0
From the date of enrolment until randomisation (approximately 24 weeks after enrolment)
Secondary outcome [4] 0 0
pCR rate
Timepoint [4] 0 0
From the date of enrolment until randomisation (approximately 24 weeks after enrolment)
Secondary outcome [5] 0 0
Proportion of patients eligible for randomisation
Timepoint [5] 0 0
From the date of enrolment until randomisation (approximately 24 weeks after enrolment)
Secondary outcome [6] 0 0
Proportion of patients effectively randomised
Timepoint [6] 0 0
From the date of enrolment until randomisation (approximately 24 weeks after enrolment)
Secondary outcome [7] 0 0
Toxicity according to CTCAE v5.0
Timepoint [7] 0 0
From the date of enrolment until randomisation (approximately 24 weeks after enrolment)
Secondary outcome [8] 0 0
DFS in patients with pCR
Timepoint [8] 0 0
From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)
Secondary outcome [9] 0 0
Overall survival (OS) in patients with/without pCR
Timepoint [9] 0 0
From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)
Secondary outcome [10] 0 0
DFS in patients with/without ctDNA clearance
Timepoint [10] 0 0
From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)
Secondary outcome [11] 0 0
Time to recurrence (TTR) in patients with/without pCR
Timepoint [11] 0 0
From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)
Secondary outcome [12] 0 0
Time to treatment discontinuation (TTD) in patients with/without pCR
Timepoint [12] 0 0
From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)
Secondary outcome [13] 0 0
Toxicity according to CTCAE v5.0
Timepoint [13] 0 0
From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)

Eligibility
Key inclusion criteria
Inclusion Criteria for enrolment:

- Histologically confirmed NSCLC.

- Stage IIB-IIIB (T1-4 N0-2) according to 8th edition of the TNM staging system of
lung cancer.

Stage III assessment should include samples of lymph nodes at levels 4, bilaterally, and
level 7 to rule out stage IIIB N3 disease.

T4 tumours will only be eligible if they are defined as T4 based only on their size
(>7cm); any other reason will be considered ineligible.

- Known PD-L1 status, as tested locally using a validated assay. To ensure
comparability of results, it is strongly encouraged that PD-L1 testing is done with
the Ventana PD-L1 (SP263) assay.

- Absence of EGFR mutation or ALK translocation, as tested locally.

- Primary tumour resectable and functionally operable as assessed per local
multidisciplinary tumour board (cardiac evaluation, pulmonary function and diffusion
capacity, comorbidity).

- Adequate haematological function:

Haemoglobin ≥90 g/L, Absolute neutrophil count (ANC) ≥1.0× 109/L, Platelet count ≥75×
109/L.

- Adequate renal function: Measured creatinine clearance (CL) >40 mL/min or calculated
CL >40 mL/min calculated by the Cockcroft-Gault.

- Adequate liver function: ALT and AST ≤2.5× institutional ULN, Total serum bilirubin
≤1.5× institutional ULN (patients with Gilbert's syndrome may be allowed to be
enrolled after consultation with the Medical Affairs Team at the ETOP IBCSG Partners
Foundation.

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

- Age ≥18 at the time of enrolment.

- Body weight >30 kg.

- Life expectancy of at least 12 weeks.

- Women of childbearing potential, including women who had their last menstruation in
the last 2 years, must have a negative urinary or serum pregnancy test at screening
before enrolment. Pregnancy test must be repeated within 3 days before the first
dose of protocol treatment.

- Written IC for study participation must be signed and dated by the patient and the
investigator prior to any study-related intervention.

Eligibility Criteria for randomisation:

- Surgical resection must have been completed. Note: Participants who have had only
had segmentectomy or wedge resections are not eligible for randomisation.

- Patients must have complete resection: R0 or R1 resection.

- Patients must be fit to receive adjuvant treatment with durvalumab.

- Patients must have no evidence of metastatic disease as assessed by CT scan.

- Documentation of pathological response as per local review must be available.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for enrolment:

- T4 with invasion of heart, great vessels, carina, trachea, oesophagus, or spine.

- Any previous or concurrent treatments for NSCLC.

- Any previous immunotherapy.

- Major surgical procedure (as per investigators assessment) within 28 days before
enrolment.

- History of allogenic organ transplantation.

- Active or prior documented autoimmune disease or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], 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 type I diabetes. Patients with
hypothyroidism (e.g., 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
Medical Affairs Team at the ETOP IBCSG Partners Foundation.

Patients with celiac disease controlled by diet alone.

- 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), or serious
chronic gastrointestinal conditions associated with diarrhoea.

- Psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the ability
of the patient to give written informed consent.

- History of another primary malignancy except for:

Malignancy treated with curative-intent and with no known active disease 5 years before
the first dose of durvalumab and of low potential risk for recurrence.

Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease.

Adequately treated carcinoma in situ without evidence of disease.

- History of leptomeningeal carcinomatosis.

- History of active primary immunodeficiency.

- Active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B
virus (HBV) surface antigen (HbsAg) or HBV core antibody (anti-HBc).

Participants with a past or resolved HBV infection (defined as the presence of anti-HBc
and absence of HbsAg) are eligible.

Participants positive for HCV antibody are only eligible if polymerase chain reaction is
negative for HCV RNA.

- Known HIV infection that is not well-controlled. All of the following criteria are
required to define an HIV infection that is well controlled: undetectable viral RNA
load for 3 months, CD4+ count of 500 cell per mm3, no history of AIDS-defining
opportunistic infection within the past 12 months, and stable for at least 3 months
on the same anti-HIV medication.

- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:

Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular
injection).

Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or
its equivalent.

Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

- Receipt of live attenuated vaccine within 30 days prior to the first dose of
durvalumab.

Note: Patients in the ADOPT-lung trial, should not receive live vaccine whilst receiving
durvalumab and for up to 30 days after the last dose.

Concurrent enrolment in another interventional clinical trial.

- Known allergy or suspected hypersensitivity to durvalumab or its excipients.

- Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions, and
requirements.

- Female patients who are pregnant or in the period of lactation.

- Female patients of childbearing potential and sexually active men who are not
willing to use a highly effective contraceptive method during the trial until at
least 90 days after the last dose of protocol treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Other
Name
ETOP IBCSG Partners Foundation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Solange Peters, MD-PhD
Address 0 0
Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Heidi Roschitzki, PhD
Address 0 0
Country 0 0
Phone 0 0
+41 31 511 94 00
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.