Study SAKK 19/17 - Durvalumab in patients with PD-L1-positive advanced non-small cell lung cancer (NSCLC) and insufficient general condition - A multicenter single-arm phase II study.

Switzerland (ICTRP)

ID di studio ICTRP
NCT03620669 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
First line durvalumab in patients with PD-L1 positive, advanced NSCLC with performance status 2 unsuitable for combination chemotherapy. A multicenter, single-arm phase II trial (BASEC)

Titolo accademico
First Line Durvalumab in Patients With PD-L1 Positive, Advanced NSCLC With Performance Status 2 Unsuitable for Combination Chemotherapy. A Multicenter, Single-arm Phase II Trial (ICTRP)

Titolo pubblico
1st Line Durvalumab in PS 2 NSCLC Patients (ICTRP)

Malattie studiate
NSCLC Stage IVNSCLC Stage IIIB (ICTRP)

Intervento studiato
Drug: Durvalumab (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Inclusion Criteria:

- Written informed consent according to Swiss law and ICH/GCP regulations before
registration and prior to any trial specific procedures

- Histologically confirmed NSCLC, advanced or recurrent disease (stage IIIB to IV).
Cytology could be accepted if histology is not possible

- PD-L1 expression of = 25% of the tumor cells by local testing (Ventana SP142
excluded)

- No sensitizing EGFR mutation (L858R or exon 19 deletions), ALK fusion oncogene or
rearrangements of the ROS1 gene detected in patients with a non-squamous cell NSCLC

- Patient unsuitable for platinum-containing combination chemotherapy according to
investigator or due to patient preference

- WHO PS of 2. Confirmation of PS2 by a second medical doctor is mandatory.

- Age = 18 years

- Baseline QoL forms and GA questionnaires have been completed

- Bone marrow function: hemoglobin = 90 g/L, neutrophil count = 1.5 x 109/L, platelet
count = 100 x 109/L

- Hepatic function: bilirubin = 1.5 x ULN (except for patients with Gilbert's disease
= 3.0 x ULN) patients without liver metastases: AST and ALT = 2.5 x ULN, patients
with documented liver metastases: AST and ALT = 5 x ULN

- Renal function: estimated glomerular filtration rate (eGFR)> 30 mL/min/1.73m
(according to CKD-EPI formula)

- Measurable or evaluable disease (by RECIST v1.1)

- Patients with asymptomatic untreated CNS metastases are eligible, provided they meet
the following:

- = 5 CNS lesions with a maximum diameter of one lesion of 10 mm

- Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons,
cerebellum, medulla, or spinal cord)

- No evidence of progression at registration compared to the latest brain imaging

- No ongoing requirement for corticosteroids as therapy for CNS disease

- Patients with symptomatic treated CNS metastases are eligible, provided they meet
the following:

- No ongoing requirement for corticosteroids as therapy for CNS disease
anticonvulsants at a stable dose allowed

- No stereotactic radiation or whole-brain radiation within 7 days prior to
registration

- No evidence of progression at registration, after completion of CNS-directed
therapy

- Tumor tissue available for central PD-L1 assessment and translational research
(preferably histology but cytology could be allowed if histology is not possible).
In case of scarce tumor material, a rebiopsy, if clinically possible, is encouraged

- Women with child-bearing potential are using effective contraception, are not
pregnant or lactating and agree not to become pregnant during trial treatment and
during the 3 months thereafter. A negative pregnancy test before inclusion into the
trial is required for all women with child-bearing potential

- Men agree not to father a child during trial treatment and during 3 months
thereafter

- Body weight > 30kg.

- Life expectancy > 3 months.

Exclusion criteria:

Any potential patient who meets any of the following criteria has to be excluded from
entering the trial.

- History of hematologic or primary solid tumor malignancy, unless in remission for at
least 3 years before registration with the exception of pT1-2 prostate cancer
Gleason score <6, adequately treated cervical carcinoma in situ or localized
non-melanoma skin cancer

- Prior adjuvant systemic anti-cancer treatment within 6 months before registration

- Prior systemic treatment for metastatic NSCLC

- Prior treatment with a PD-1 or PD-L1 inhibitor

- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses (i.e. which must not exceed 10
mg/day of prednisone or an equivalent corticosteroid)

- Concomitant drugs contraindicated for use with durvalumab such as corticosteroids,
methotrexate, azathioprine and tumor necrosis factor (TNF)-a blockers

- Concurrent treatment with other experimental drugs or other anticancer therapy,
treatment in a clinical trial within 28 days prior to registration

- Major surgical procedure within 14 days prior to registration

- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., 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 (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 coordinating investigator

- Patients with celiac disease controlled by diet alone

- Uncontrolled diabetes mellitus

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment

- Known history of tuberculosis

- Known history of primary immunodeficiency

- Known history of allogeneic organ transplant

- Receipt of live attenuated vaccine within 28 days prior to registration

- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
IV unstable angina pectoris, history of myocardial infarction within the last six
months, serious arrhythmias requiring medication (with exception of atrial
fibrillation or paroxysmal supraventricular tachycardia), significant
QT-prolongation, uncontrolled hypertension

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.

- Patients with dyspnea grade = 3 according to the modified Medical Research Council
(mMRC) dyspnea scale.

- Patients with symptomatic pneumonitis (grade = 2) or active lung infection. Patients
having fully recovered from active lung infection can be included assumed they have
completed antibiotics and/or corticosteroids

- Patients with disseminated intravascular coagulopathy

- Patient with a baseline CT scan older than 21 days prior to registration. (ICTRP)

non disponibile

Endpoint primari e secondari
Overall survival (OS) at 6 months (ICTRP)

Objective response (OR) according to RECIST 1.1;Objective response according to iRECIST (iOR);Duration of response (DoR) according to RECIST 1.1;Duration of response according to iRECIST (iDoR);Progression-free survival (PFS) according to RECIST 1.1;Progression-free survival according to iRECIST (iPFS);Overall survival (OS);Adverse events (AEs);Quality of life (QoL): Core 30 (QLQ-C30);Geriatric assessment (GA) - Screening instrument (G8);Geriatric assessment (GA) - Assessment with IADL;Geriatric assessment (GA) (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Michael Mark, MD, Kantonsspital Graubnden (ICTRP)

ID secondari
SAKK 19/17 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT03620669 (ICTRP)