Alectinib in Neo-adjuvant Treatment of Stage III NSCLC

NCT05015010 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: GOIRC-01-2020
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

Non Small Cell Lung Cancer

Keywords

ALK-positive; NSCLC

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR)

  Percentage of residual viable tumor cells histologically detected in the resected primary tumor and all resected lymph nodes after surgery ≤10%. Evaluation by Blinded Independent Pathology Reviewer (BIPR).

  From the treatment start until surgery - 12 weeks period (8 weeks of neoadjuvant therapy; surgery should be done within 2-4 weeks afterwards.

Secondary Outcomes (7)

• Pathological Complete Response

  From the treatment start until surgery - 12 weeks period (8 weeks of neoadjuvant therapy; surgery should be done within 2-4 weeks afterwards.

• Objective response

  Pre-surgical radiological evaluation (after 8 weeks of neoadjuvant therapy start)

• Event-free survival (EFS)

  From the trial inclusion date to either the date of disease recurrence/progression or the date of death, monitored up to 3 years after surgery.

• Disease-free survival (DFS)

  From the date of surgical resection to either the date of disease recurrence or the date of death monitored up to 3 years after surgery.

• Overall survival (OS)

  From the date of trial inclusion to the date of death monitored up to 3 years after surgery.

Study Arms (1)

Alectinib

EXPERIMENTAL

The treatment will be administrated as neoadjuvant 8 weeks before surgery. After surgical intervention the treatment will be administered up to 96 weeks. Treatment will be discontinued in case of unacceptable toxicity or disease progression.

Drug: Alectinib

Interventions

Alectinib DRUG

600 mg p.o. (four 150 mg capsules) twice daily with food (within 30 minutes after a meal, in the morning and evening).

Alectinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead

Study Sites (20)

IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - I.R.S.T.

Meldola, Forlì-Cesena, 47014, Italy

Location

UOC Oncologia Medica Ospedale Versilia USL Toscana Nord Ovest

Lido di Camaiore, Lucca, 55041, Italy

Location

A.S.S.T - Monza Ospedale San Gerardo

Monza, Monza Brianza, 20900, Italy

Location

Centro di Riferimento Oncologico (CRO) - IRCCS Aviano

Aviano, Pordenone, Italy

Location

SSD oncologia polmonare - AOU San Luigi Gonzaga

Orbassano, Torino, 10043, Italy

Location

IRCCS Istittuo Tumori Giovanni Paolo II

Bari, 70124, Italy

Location

Azienda Ospedaliero Universitaria Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Oncologia Medica - PO Rodolico -AOU "Policlinico - Vittorio Emanuele"

Catania, 95125, Italy

Location

SODc Oncologia Medica - Azienda Ospedaliera-Universitaria Careggi

Florence, Italy

Location

Oncologia Medica 2 - IRCCS AOU Policlinico San Martino - IST

Genova, 16132, Italy

Location

Dipartimento Oncologia e Ematologia - Azienda Ospedaliero-Universitaria di Modena

Modena, 41124, Italy

Location

U.O.C Pneumologia ad Indirizzo Oncologico - Azienda Ospedaliera Dei Colli

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto (IOV)

Padua, 35128, Italy

Location

UOC di Oncologia Medica - AOU di Parma

Parma, 43126, Italy

Location

Ospedale S. Maria della Misericordia

Perugia, 06129, Italy

Location

IFO Istituto Regina Elena

Roma, 00144, Italy

Location

UOSD Pneumologia Oncologica- Ospedale San Camillo

Roma, 00152, Italy

Location

Fondazione Policlinico Universitario 'A. Gemelli' IRCCS. Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

Humanitas Research Hospital - Medical Oncology

Rozzano, 20089, Italy

Location

Dipartimento di Oncologia Medica - Università di Verona

Verona, 37135, Italy

Location

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Related Links

• Lung Cancer Survival Rates: 5-Year Survival Rates for Lung Cancer
• National Comprehensive Cancer Network. Non-small cell lung cancer (Version 3.2020).

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: August 20, 2021
• Study Start: May 20, 2021
• Primary Completion: December 28, 2024
• Study Completion (Estimated): December 28, 2026
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (20)