Study SAKK 15/19 Radiation therapy of lung tumors and maintenance therapy with Durvalumab following treatment with chemotherapy and Durvalumab in patients with advanced small cell lung cancer

Switzerland (ICTRP)

ICTRP Studien-ID
NCT04472949 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
Thoracic radiotherapy plus maintenance Durvalumab after first line Carboplatin and Etoposide plus Durvalumab in extensive-stage disease small cell lung cancer (ED-SCLC). A multicenter single arm open label phase II trial. (BASEC)

Wissenschaftlicher Titel
Thoracic Radiotherapy Plus Maintenance Durvalumab After First Line Carboplatin and Etoposide Plus Durvalumab in Extensive-stage Disease Small Cell Lung Cancer (ED-SCLC). A Multicenter Single Arm Open Label Phase II Trial. (ICTRP)

Öffentlicher Titel
Thoracic Radiotherapy Plus Maintenance Durvalumab After First Line Carboplatin and Etoposide Plus Durvalumab in Extensive-stage Disease Small Cell Lung Cancer (ED-SCLC). (ICTRP)

Untersuchte Krankheit(en)
Small Cell Lung CancerLung Cancer (ICTRP)

Untersuchte Intervention
Drug: DurvalumabDrug: carboplatinDrug: etoposideRadiation: Thoracic radiotherapy (ICTRP)

Studientyp
Interventional (ICTRP)

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

Ein-/Ausschlusskriterien
Inclusion Criteria:

- Written informed consent according to Swiss law and ICH-GCP E6(R2) regulations
before registration and prior to any trial specific procedures

- Histologically or cytologically1 confirmed extensive disease stage IV SCLC (T any, N
any, M1 a/b) or T3-4 due to multiple lung nodules that are too extensive or have
tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan
(according to American Joint Committee on Cancer Stage (8th edition)

- Patients must be considered suitable to receive carboplatin with etoposide as 1st
line treatment for the ED-SCLC

- Patients with brain metastases are also eligible provided they are asymptomatic or
treated central nervous system metastases and meet the following criteria:

- No ongoing requirement for corticosteroids at least 2 weeks prior to trial
treatment

- No leptomeningeal disease

- Patients with a prior malignancy other than SCLC and treated with curative intention
are eligible, if all treatment of that malignancy was completed at least 2 years
before registration and the patient has no evidence of disease at registration. Less
than 2 years is acceptable for malignancies with low risk of recurrence and/or no
late recurrence, after consultation with the Coordinating Investigator

- Measurable disease per RECIST v1.1

- Age = 18 years

- WHO performance status 0-1

- Adequate pulmonary function: forced expiratory volume in one second FEV (1) = 1.0
liter

- Adequate bone marrow function:

- Absolute neutrophil count = 1.5 x 109/L1

- Platelet count = 100 x 109/L

- Hemoglobin = 90 g/L

- Adequate hepatic function:

- Total bilirubin = 1.5 x ULN (except for patients with Gilbert's disease = 3.0 x
ULN)

- AST and/or ALT = 2.5 x ULN (in patients with hepatic metastasis: AST and/or ALT
= 5.0 x ULN)

- Adequate renal function measured (by the CKD-EPI formula) or calculated creatinine
clearance = 45 mL/min (by the Cockcroft-Gault formula)

- Women of childbearing potential must use highly effective contraception, are not
pregnant or lactating and agree not to become pregnant during trial treatment and
until 90 days after the last dose of investigational drug. A negative serum
pregnancy test performed within 7 days before registration is required for all women
of childbearing potential

- Men agree not to donate sperm or to father a child during trial treatment and until
90 days after the last dose of investigational drug

Exclusion criteria:

- Spinal cord compression not definitively treated with surgery and/or radiation or
previously diagnosed and treated spinal cord compression without evidence that
disease has been clinically stable for = 1 week prior to registration

- Prior chemotherapy treatment for ED-SCLC

- Any history of radiotherapy to the chest. Radiation therapy outside of the chest for
palliative care (i.e., bone metastasis) is allowed but must be completed before
first dose of -

- Prior systemic treatment including immune checkpoint inhibitors against SCLC

- Concomitant treatment within 30 days of registration with any other experimental
drug and/or enrollment in another clinical trial

- Concomitant use of other anti-cancer drugs or radiotherapy. Except surgery for local
pain control

- Severe or uncontrolled cardiovascular disease

- Congestive heart failure NYHA III or IV

- Unstable angina pectoris

- History of myocardial infarction within the last 3 months

- Serious arrhythmias requiring medication (with exception of atrial fibrillation
or paroxysmal supraventricular tachycardia)

- Uncontrolled hypertension

- Uncontrolled or symptomatic hypercalcemia, i.e.

- > 1.5 mmol/L ionized calcium

- > 12 mg/dL or > 3 mmol/L corrected serum calcium

- Known interstitial lung disease

- Body weight = 30 kg

- Major surgical procedure (defined by the investigator) within 28 days prior to the
first dose of durvalumab or anticipation of need for a major surgical procedure
during the course of the trial

- Known history of active primary immunodeficiency

- 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 antimicrobial treatment

- Known history of allogeneic organ transplantation

- Active or prior documented autoimmune or inflammatory disorders including:

- Inflammatory bowel disease (e.g., colitis or Crohn's disease)

- Systemic lupus erythematosus

- Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc.)

- Patients with eczema, psoriasis, lichen simplex chronicus are not permitted, except
they are with dermatologic manifestations only (e.g., patients with psoriatic
arthritis would be excluded) and meet the following conditions:

- Rash must cover less than 10% of body surface area

- Disease is well controlled at baseline and only requires low potency topical
steroids

- No acute exacerbations of underlying condition within the last 12 months (not
requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors, high potency, or oral
steroids)

- Patients with a paraneoplastic syndrome (PNS) of autoimmune nature, requiring
systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical
symptomatology suggesting worsening of PNS

- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening thorax CT scan

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

- Concomitant or prior use, i.e. within 14 days before the first dose of durvalumab,
of immunosuppressive medication including immunosuppressant, such as methotrexate,
azathioprine and tumor necrosis factor (TNF)-a blockers, with the exceptions of:

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

- Systemic corticosteroids at physiological doses not to exceed 10 mg/day of
prednisone or an equivalent corticosteroid

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

- Known hypersensitivity to the drugs used in this trial (carboplatin, etoposide,
durvalumab)

- 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 comp (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Progression-free rate (PFR) (RECIST v.1.1) (ICTRP)

Progression-free survival (PFS) (RECIST v.1.1);Progression-free survival (PFS) (RECIST v.1.1) outside the brain;Progression-free survival (RECIST v.1.1) after induction chemotherapy (PFS-IND);Overall Survival (OS);Objective response rate (ORR);Duration of response (DOR);Adverse events (AEs) (ICTRP)

Registrierungsdatum
nicht verfügbar

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Alfredo Addeo, Prof, Hpitaux Universitaires Genve (ICTRP)

Sekundäre IDs
SAKK 15/19 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT04472949 (ICTRP)