Patologia: Neoplasie del polmone
Fase di studio: II
Linee di trattamento: Adiuvante/neoadiuvante
Criteri di inclusione:
All of the following criteria have to be satisfied to include patients into the study:
1. Male or female, aged ≥ 18 years.
2. Histologically or cytologically confirmed adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is thepredominant histology.
3. Documented ALK-positive disease according to an FDA-approved and CE-marked test.
4. Locally advanced NSCLC in stage III according to the 8th American Joint Committee on Cancer TNM edition, defined potentially
resectable (any T with N2, T4N0-1).
5. Documentation that the patient is a candidate for surgical resection of their lung cancer after multidisciplinary discussion.
6. Patients must be treatment-naive for NSCLC and eligible to receive treatment with Alectinib.
7. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria with CT scan.
8. Brain magnetic resonance imaging (MRI) or CT scan showing no evidence of metastatic disease.
9. Positron emission tomography (PET)-computed tomography (CT) showing radiographic stage III lung cancer (mediastinal staging biopsy is allowed but not required).
10. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1.
11. Ability to swallow oral medications.
12. Adequate haematological function defined by white blood cell (WBC) count ≥ 2.500/mm3 with absolute neutrophil count (ANC) ≥1.500/mm3, platelet count ≥ 100.000/mm3 and haemoglobin ≥ 9 g/dL.
13. Adequate hepatic function defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN) range (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL), serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 if liver function test elevations are due to liver metastases).
14. Adequate renal function defined by a serum creatinine ≤ 1.5 x ULN or an estimated creatinine clearance of ≥ 30 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft-Gault formula).
15. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before trial inclusion date, and otherwise noted in other inclusion/exclusion criteria.
16. Female patients with childbearing potential should be using adequate contraceptive measures and should not be breastfeeding
during the study and for 90 days following the last dose of Alectinib. They and must have a negative serum pregnancy test
within 7 days prior to the first dose of study drug.
17. Female patients must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all
exogenous hormonal treatments;
- Women under 50 years old would be considered post-menopausal if they have been amenorrheic for 12 months or
more following cessation of exogenous hormonal treatment with LH and FSH levels in the post-menopausal range for the
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
18. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective
contraception as described in the full protocol for at least 14 days prior to administration of the first dose of study treatment, during the study, and for 90 days following the last dose of Alectinib.
19. Ability to comply with protocol requirements
20. The patient is able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care.
Criteri di esclusione:
Subjects are not eligible for this trial if they fulfil any of the following exclusion criteria:
1. Prior treatment with any systemic anti-cancer therapy for locally advanced NSCLC including chemotherapy, biologic therapy,
including ALK-TKI, immunotherapy or any investigational drug.
2. Non-resectable stage III and stage IV disease with distant metastases (including malignant pleural effusion) identified on PET-CT scan or biopsy.
3. Any concurrent and/or active malignancy that has required treatment within 2 years of the first dose of study drug.
4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol; or known active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV); screening for chronic conditions is not required; patients with chronic hepatitis B virus (HBV) with negative HBV viral load on appropriate antiviral therapy will be permitted, if able to continue appropriate antiviral therapy throughout treatment period.
5. Any severe infection, including COVID-19, within 4 weeks prior to initiation of study treatment, including, but not limited to,
hospitalization for complications of infections.
6. History of organ transplant.
7. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Alectinib.
8. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc)>470 msec, obtained from 3 electrocardiograms (ECGs)
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch
block, third-degree heart block, second-degree heart block, PR interval >250msec, symptomatic bradycardia <45 beats/minute.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia,
congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in
first-degree relatives or any concomitant medication known to prolong the QT interval.
9. Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry.
10. History of hypersensitivity to active or inactive excipients of Alectinib
or drugs with a similar chemical structure or class to Alectinib. This includes, but is not limited to, patients with galactose intolerance, a congenital lactase deficiency or glucose-galactose malabsorption.
11. Administration of strong/potent cytochrome P450 (CYP)3A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with Alectinib except for oral corticosteroids up to 20 mg of prednisolone equivalent per day.
12. Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site).
13. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
Numero di pazienti previsti:
Schema di trattamento:
Patients with potentially resectable locally advanced stage III ALK-positive NSCLC will be treated with oral Alectinib 600 mg twice daily for two cycles of 4 weeks each (8 weeks) in the absence of clinical progression or unacceptable toxicity, followed by a radiological assessment and surgical resection if no progressive disease will be documented. Surgery is planned to take place within 3 weeks ± 1 week after completion of neoadjuvant period.
After surgery, patients will receive Alectinib for 96 weeks. Blood samples for molecular analyses will be collected at baseline, 4 weeks and 8 weeks of neoadjuvant Alectinib treatment, after surgery (within 2 weeks) and at the eventual relapse.
Trattamento di controllo:
Obiettivi primari dello studio:
To assess the activity as major pathologic response of single-agent Alectinib as neoadjuvant treatment in patients with ALK-positive potentially resectable locally advanced stage III NSCLC.
Obiettivi secondari dello studio:
- To evaluate the pathological downsizing and the complete resectability with neoadjuvant Alectinib.
- To evaluate the activity of Alectinib as neo-adjuvant treatment in terms of objective response.
- To evaluate long-term measures of efficacy of Alectinib as neoadjuvant and adjuvant treatment.
- To assess the safety and tolerability profile of Alectinib as neoadjuvant and adjuvant treatment.
Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO
UOC di Oncologia Medica
IRCCS - IRST
Via P. Maroncelli 40 - 47014 Meldola - FC
Istituto Scientifico Romagnolo
IRCCS A.O.U. San Martino - IST
Largo Rosanna Benzi 10 - 16132 Genova - GE
UOS Tumori polmonari - UO Oncologia Medica 2
Istituto Clinico Humanitas Rozzano
Via Manzoni 56 - 20089 Rozzano - MI
A.O.U. Policlinico di Modena
Via del Pozzo 71 - 41100 Modena - MO
Dip Oncologia-Ematologia - UO Oncologia
Riferimento: Dr. Fausto Barbieri
A.O. San Gerardo
Via Pergolesi 33 - 20900 Monza - MB
Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
UOC Oncologia Medica 2
Riferimento: Dr.ssa Giulia Pasello
Azienda Ospedaliero-Universitaria di Parma
Via Gramsci 14 - 43126 Parma - PR
UOC di Oncologia Medica
Riferimento: Dr. Marcello Tiseo
Centro di Riferimento Oncologico
Via Franco Gallini 2 - 33081 Aviano - PN
Unità org. semplice dei tumori del polmone e pleura
Riferimento: Dr.ssa Alessandra Bearz
A.O.U San Luigi Gonzaga
Regione Gonzole 10 - 10043 Orbassano - TO
SSD Oncologia polmonare
AOUI Verona - Borgo Trento
Piazzale Aristide Stefani 1 - 37126 Verona - VR
Largo Brambilla 3 - 50134 Firenze - FI
SOD Oncologia Medica
Riferimento: Dr.ssa Francesca Mazzoni
Via Aurelia 335 - 55041 Lido di Camaiore - LU
UOC Oncologia Medica
Riferimento: Dr. Andrea Camerini
Azienda Ospedaliera di Perugia
Via Dottori 1 - 06132 Perugia - PG
Riferimento: Dr. Giulio Metro
Azienda Ospedaliera San Camillo Forlanini
Via Portuense 332 - 00149 Roma - RM
UOSD Pneumologia Oncologica
Riferimento: Dr.ssa Maria Rita Migliorino
Fondazione Policlinico A. Gemelli
Largo Agostino Gemelli 8 - 00168 Roma - RM
Istituto Nazionale Tumori “Regina Elena”
Via Elio Chianesi 53 - 00144 Roma - RM
Oncologia Medica 1
Riferimento: Dr.ssa Fabiana Letizia Cecere
Istituto Tumori “Giovanni Paolo II” IRCCS
Viale Orazio Flacco 65 - 70124 Bari - BA
SSD Oncologia Medica per la patologia toracica
Riferimento: Dr. Domenico Galetta
AOU Policlinico Vittorio Emanuele PO G. Rodolico
Via S. Sofia 78 - 95123 Catania - CT
Riferimento: Dr. Hector Soto Parra
Azienda Ospedaliera Vincenzo Monaldi
Via Leonardo Bianchi 1 - 80131 Napoli - NA
UOC Pneumologia ad indirizzo oncologico
Numero di iscrizione a registro: NA
Data di inserimento: 11.06.2021
Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)
Azienda Ospedaliera Universitaria, Parma
Riferimento: Dr. Marcello Tiseo