ALECTINIB for Non-small cell lung cancer (ALK-positive, locally advanced Stage III)

Inclusion criteria

• {"criterion_text":"- Male or female, aged >= 18 years\n- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 1.\n- Ability to swallow oral medications.\n- 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.\n- 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).\n- 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).\n- 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\n- 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.\n- Female patients must have evidence of non child bearing potential by fulfilling\n- 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 t he study, and for 90 days following the last dose of Alectinib.\n- Ability to comply with protocol requirements.\n- Histologically or cytologically confirmed adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.\n- 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 w ithout prejudice to future medical care.\n- Documented ALK positive disease according to an FDA approved and CE marked test.\n- 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)\n- Documentation that the patient is a candidate for surgical resection of their lung cancer after multidisciplinary discussion.\n- Patients must be treatment naive for NSCLC and eligible to receive treatment with Alectinib.\n- Measurable disease defined by Response Evaluation Criteria in Solid Tumor s (RECIST) 1.1 criteria with CT scan.\n- Brain magnetic resonance imaging (MRI) or CT scan showing no evidence of metastatic disease.\n- Positron emission tomography (PET) computed tomography (CT) showing radiographic stage III lung cancer (mediastinal staging biopsy is allowed but not required)."}

Exclusion criteria

• {"criterion_text":"- Prior treatment with any systemic anti cancer therapy for locally advanced NSCLC including chemotherapy, biologic therapy, including ALK TKI, immunotherapy or any investigational drug.\n- Non resectable stage III and stage IV disease with distant metastases (including malignant pleural effusion) identified on PET CT scan or biopsy.\n- Any concurrent and/or active malignancy that has required treatment within 2 years of the first dose of study drug.\n- 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 comp liance 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 a ppropriate antiviral therapy will be permitted, if able to continue appropriate antiviral therapy throughout treatment period.\n- 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.\n- History of organ transplant\n- 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.\n- Any of the following cardiac criteria: Mean resting corrected QT interval (QTc)>470 msec, obtained from one electrocardiogram (ECG) 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 relati ves or any concomitant medication known to prolong the QT interval.\n- 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.\n- 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 glucos e galactose malabsorption.\n- 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.\n- Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site).\n- 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."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is m ajor pathologic response (MPR), defined as <=10% residual viable tumor cells histologically detected in the resected primary tumor and all resected lymph nodes after surgery","definition_or_measurement_approach":"Major pathologic response (MPR) defined as ≤10% residual viable tumor cells histologically detected in the resected primary tumor and all resected lymph nodes after surgery; assessment on resected surgical specimens."}

Secondary endpoints

• {"endpoint_text":"- Pathological complete response - Pathological complete response (pCR) is defined as the absence of residual viable tumor cells in all specimens as evaluated by BIPR after surgery","definition_or_measurement_approach":"Pathological complete response (pCR) defined as absence of residual viable tumor cells in all specimens as evaluated by blinded independent pathological review (BIPR) after surgery."}

Italy

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

02-12-2024

Processing Time Days

35

Number Of Sites

19

Number Of Participants

33

Primary sponsor

Full Name

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"ROCHE S.P.A.","duties_or_roles":"Source of monetary support","organisation_type":""}