Phase II, open label, single arm, multicenter study to assess the activity and safety of ALectinib as NE O adjuvant therapy in patients with anaplastic lymphoma kinase positive (ALK+) locally advanced Stage III Non Small Cell Lung Cancer (NSCLC): ALNEO trial-GOIRC-01-2020

Phase 2

Not yet recruiting

• Conditions: Patients with anaplastic lymphoma kinase positive (ALK+) locally advanced Stage III Non Small Cell Lung Cancer (NSCLC)

• Registration Number: 2024-519106-12-00
• Lead Sponsor: G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-12-02
• Last Update Posted: 2024-12-02

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 33

Inclusion Criteria

Male or female, aged >= 18 years

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

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.

Ability to comply with protocol requirements.

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

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.

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 Tumor s (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).

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.

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.

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.

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 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.

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 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.

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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		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

Secondary Outcome Measures

Name	Time	Method
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		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

Trial Locations

Locations (19)

Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania; 🇮🇹 Catania, Italy

Azienda Ospedaliero Universitaria Parma; 🇮🇹 Parma, Italy

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico; 🇮🇹 Bologna, Italy

Azienda Ospedaliero Universitaria Di Modena; 🇮🇹 Modena, Italy

Istituto Tumori Bari Giovanni Paolo II; 🇮🇹 Bari, Italy

Azienda Ospedaliero Universitaria Careggi; 🇮🇹 Florence, Italy

Azienda Ospedaliera Dei Colli; 🇮🇹 Naples, Italy

Centro Di Riferimento Oncologico Di Aviano; 🇮🇹 Aviano, Italy

San Camillo Forlanini Hospital; 🇮🇹 Rome, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Rome, Italy

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Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania

🇮🇹Catania, Italy

Hector Soto Parra

Site contact

00390953781496

hsotoparra@policlinico.unict.it