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Non Small Cell Lung CancerPhase 2ALNEONCT05015010

Alectinib in Neo-adjuvant Treatment of Stage III NSCLC

A Phase 2 study testing Alectinib in people with Non Small Cell Lung Cancer, run by Gruppo Oncologico Italiano di Ricerca Clinica at 20 sites in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Alectinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
20 sitesItaly
Study dates
20 May 2021to 28 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 23Show fewer
  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

Italy20 sites

  • Centro di Riferimento Oncologico (CRO) - IRCCS Aviano

    Aviano, Pordenone

  • IRCCS Istittuo Tumori Giovanni Paolo II

    Bari, 70124

  • Azienda Ospedaliero Universitaria Policlinico S.Orsola-Malpighi

    Bologna, 40138

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

    Catania, 95125

  • SODc Oncologia Medica - Azienda Ospedaliera-Universitaria Careggi

    Florence

  • Oncologia Medica 2 - IRCCS AOU Policlinico San Martino - IST

    Genova, 16132

  • UOC Oncologia Medica Ospedale Versilia USL Toscana Nord Ovest

    Lido di Camaiore, Lucca, 55041

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

    Meldola, Forlì-Cesena, 47014

  • Dipartimento Oncologia e Ematologia - Azienda Ospedaliero-Universitaria di Modena

    Modena, 41124

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

    Monza, Monza Brianza, 20900

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

    Naples, 80131

  • SSD oncologia polmonare - AOU San Luigi Gonzaga

    Orbassano, Torino, 10043

  • Istituto Oncologico Veneto (IOV)

    Padova, 35128

  • UOC di Oncologia Medica - AOU di Parma

    Parma, 43126

  • Ospedale S. Maria della Misericordia

    Perugia, 06129

  • IFO Istituto Regina Elena

    Roma, 00144

  • UOSD Pneumologia Oncologica- Ospedale San Camillo

    Roma, 00152

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

    Roma, 00168

  • Humanitas Research Hospital - Medical Oncology

    Rozzano, 20089

  • Dipartimento di Oncologia Medica - Università di Verona

    Verona, 37135

Other trials in Italy

About this study

Official title: 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

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.

Being tested
Alectinib
Keywords
ALK-positive, NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlectinibDrug

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

Study groups in NCT05015010
Study groupRoleWhat they receive
AlectinibExperimentalThe 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.
Receives: Drug: Alectinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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)

  1. Pathological Complete Response

    The absence of residual viable tumor cells in all surgical specimens (resected primary tumor and all resected lymph nodes) as evaluated by BIPR.

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

  2. Objective response

    Complete Response (CR) or a Partial Responses (PR) based on the Investigator's assessment and measured according to standard RECIST criteria v1.1

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

  3. Event-free survival (EFS)

    The length of time after the trial inclusion the patient remains free of recurrence/progression or death, whatever the cause.

    Measured: 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.

  4. Disease-free survival (DFS)

    The length of time after surgical resection the patient remains free of recurrence/progression or death, whatever the cause.

    Measured: 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.

  5. Overall survival (OS)

    The length of time after the trial inclusion the patient remains alive

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

  6. Adverse Events (AE)

    Untoward medical events occurring after trial inclusion. Adverse Events are defined and graded according to Common Terminology Criteria for Adverse Events [CTCAE] version 5.0.

    Adverse event of special interest are cases of potential drug-induced liver, suspected transmission of an infectious agent by the study treatment, Interstitial Lung Disease.

    Serious adverse events is any AE occurring at any dose that results in death; is life-threatening (i.e., in the opinion of the Investigator, the subject is at immediate risk of death from the AE); requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay); results in persistent or significant disability/incapacity (a substantial disruption of the subject's ability to conduct normal life functions); is a congenital anomaly/birth defect; constitutes an important medical event.

    Measured: From the date of the trial inclusion until 30 days (90 days in case of AE serious/special interest) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first

  7. Tissue and cell-free (plasma) biomarkers

    Characterization of Anaplastic Lymphoma Kinase fusion partner on DNA extracted from tissue biopsy and on cell-free nucleic acid (cfNA) (both cfDNA and cfRNA) extracted from plasma sample.

    Measured: From the time of diagnosis up to 3 years after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2021
  2. Study start20 May 2021
  3. Primary completion28 Dec 2024 (estimated)
  4. Study completion28 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05015010
Sponsor's protocol ID
GOIRC-01-2020
Acronym
ALNEO
Status last verified
Aug 2024
First submitted
16 Aug 2021
Last updated
9 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019 Jan;69(1):7-34. doi: 10.3322/caac.21551. Epub 2019 Jan 8.

    PubMed 30620402

  • Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The Eighth Edition Lung Cancer Stage Classification. Chest. 2017 Jan;151(1):193-203. doi: 10.1016/j.chest.2016.10.010. Epub 2016 Oct 22.

    PubMed 27780786

  • Huber RM, De Ruysscher D, Hoffmann H, Reu S, Tufman A. Interdisciplinary multimodality management of stage III nonsmall cell lung cancer. Eur Respir Rev. 2019 Jul 8;28(152):190024. doi: 10.1183/16000617.0024-2019. Print 2019 Jun 30.

    PubMed 31285288

  • Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, Escriu C, Peters S; ESMO Guidelines Committee. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv1-iv21. doi: 10.1093/annonc/mdx222. No abstract available.

    PubMed 28881918

  • Nicholson AG, Chansky K, Crowley J, Beyruti R, Kubota K, Turrisi A, Eberhardt WE, van Meerbeeck J, Rami-Porta R; Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the Clinical and Pathologic Staging of Small Cell Lung Cancer in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016 Mar;11(3):300-11. doi: 10.1016/j.jtho.2015.10.008. Epub 2015 Dec 24.

    PubMed 26723244

  • Rocco G, Nason K, Brunelli A, Varela G, Waddell T, Jones DR. Management of stage IIIA (N2) non-small cell lung cancer: A transatlantic perspective. J Thorac Cardiovasc Surg. 2016 May;151(5):1235-8. doi: 10.1016/j.jtcvs.2016.01.035. Epub 2016 Mar 17. No abstract available.

    PubMed 26997100

  • Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

    PubMed 28885881

  • Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol. 2017 Feb 10;8(1):1-20. doi: 10.5306/wjco.v8.i1.1.

    PubMed 28246582

  • Lewis J, Gillaspie EA, Osmundson EC, Horn L. Before or After: Evolving Neoadjuvant Approaches to Locally Advanced Non-Small Cell Lung Cancer. Front Oncol. 2018 Jan 23;8:5. doi: 10.3389/fonc.2018.00005. eCollection 2018.

    PubMed 29410947

  • NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet. 2014 May 3;383(9928):1561-71. doi: 10.1016/S0140-6736(13)62159-5. Epub 2014 Feb 25.

    PubMed 24576776

  • Situ D, Lin Y. Neoadjuvant strategy for stage IIIA-N2 non-small cell lung cancer: chemoradiation or chemotherapy alone? J Thorac Dis. 2017 Sep;9(9):2746-2748. doi: 10.21037/jtd.2017.08.23. No abstract available.

    PubMed 29221230

  • Muller IB, de Langen AJ, Giovannetti E, Peters GJ. Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib. Onco Targets Ther. 2017 Sep 13;10:4535-4541. doi: 10.2147/OTT.S109493. eCollection 2017.

    PubMed 28979145

  • Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1;390(10089):29-39. doi: 10.1016/S0140-6736(17)30565-2. Epub 2017 May 10.

    PubMed 28501140

  • Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Perol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. doi: 10.1056/NEJMoa1704795. Epub 2017 Jun 6.

    PubMed 28586279

  • Sakamoto H, Tsukaguchi T, Hiroshima S, Kodama T, Kobayashi T, Fukami TA, Oikawa N, Tsukuda T, Ishii N, Aoki Y. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90. doi: 10.1016/j.ccr.2011.04.004.

    PubMed 21575866

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alectinib in people with Non Small Cell Lung Cancer, run by Gruppo Oncologico Italiano di Ricerca Clinica at 20 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Pathological Response (MPR) (time frame: From the treatment start until surgery - 12 weeks period (8 weeks of neoadjuvant therapy; surgery should be done within 2-4 weeks afterwards.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05015010, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.

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