Phase II, open-label, single-arm, multicenter study to assess the activity and safety of ALectinib as NEO-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
- Conditions
- patients with ALK-positive potentially resectable locally advanced stage III NSCLCMedDRA version: 21.1Level: PTClassification code 10029519Term: Non-small cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003432-25-IT
- Lead Sponsor
- GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 33
1. Male or female, aged ³ 18 years.
2. Histologically or cytologically confirmed adenocarcinoma of the lung.Patients with mixed histology are eligible if adenocarcinoma is the predominant 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 advanced Stage III NSCLC resectable
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
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 CockcroftGault 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 postmenopausal 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 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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: To evaluate the pathological downsizing and the complete resectability with neoadjuvant Alectinib.<br>• To evaluate the activity of Alectinib as neo-adjuvant treatment in terms of objective response.<br>• To evaluate long-term measures of efficacy of Alectinib as neoadjuvant and adjuvant treatment.<br>• To assess the safety and tolerability profile of Alectinib as neoadjuvant and adjuvant treatment;Primary end point(s): rimary Endpoint The primary endpoint is major pathologic response (MPR), defined as<or =10% residual viable tumor cells histologically detected in the resected primary tumor and all resected lymph nodes after surgery;Timepoint(s) of evaluation of this end point: Bone surgery and the anatomo-pathological evaluation of the surgical piece
- Secondary Outcome Measures
Name Time Method