Overview

Alectinib in Neo-adjuvant Treatment of Stage III NSCLC

Status:
Recruiting
Trial end date:
2026-05-28
Target enrollment:
0
Participant gender:
All
Summary
Stage III NSCLC is a heterogeneous group of tumors with a wide spectrum of clinical presentations. Across this wide spectrum of heterogeneity, there is no single definitive therapeutic approach and the definition of the most effective treatment approach needs a multidisciplinary approach. In this trial we want to test in ALK positive stage III locally advanced NSCLC patients, the efficacy of Alectinib to induce tumor shrinkage when administered before surgery and to reduce the possibility of disease recurrence, with a limited risk of toxicity related, in long term administration after surgery.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Gruppo Oncologico Italiano di Ricerca Clinica
Criteria
Inclusion Criteria:

- Age ≥ 18 years.

- Histologically or cytologically confirmed adenocarcinoma of the lung. Patients with
mixed histology are eligible if adenocarcinoma is the predominant histology.

- Documented ALK-positive disease according to an FDA-approved and CE-marked test.

- 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).

- Documentation that the patient is a candidate for surgical resection of their lung
cancer after multidisciplinary discussion.

- Patients must be treatment-naive for NSCLC and eligible to receive treatment with
Alectinib.

- Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST)
1.1 criteria with CT scan.

- Brain magnetic resonance imaging (MRI) or CT scan showing no evidence of metastatic
disease.

- Positron emission tomography (PET)-computed tomography (CT) showing radiographic stage
III lung cancer (mediastinal staging biopsy is allowed but not required).

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1.

- Ability to swallow oral medications.

- 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.

- 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).

- 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).

- 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.

- 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.

- 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
institution;

- Documentation of irreversible surgical sterilization by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy but not tubal ligation.

- Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception 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.

- Ability to comply with protocol requirements.

- Ability 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.

Exclusion Criteria:

- Prior treatment with any systemic anti-cancer therapy for locally advanced NSCLC
including chemotherapy, biologic therapy, including ALK-TKI, immunotherapy or any
investigational drug.

- Non-resectable stage III and stage IV disease with distant metastases (including
malignant pleural effusion) identified on PET-CT scan or biopsy.

- Any concurrent and/or active malignancy that has required treatment within 2 years of
the first dose of study drug.

- 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 (HBV),
hepatitis C (HCV) and human immunodeficiency virus (HIV); screening for chronic
conditions is not required; patients with HBV with negative HBV viral load on
appropriate antiviral therapy will be permitted, if able to continue appropriate
antiviral therapy throughout treatment period.

- 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.

- History of organ transplant.

- 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.

- 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.

- 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.

- 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.

- 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.

- Involvement in the planning and/or conduct of the study (applies to both investigator
staff and/or staff at the study site).

- 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.