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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ROCHE S.P.A.

External identifiers

EU CT number

2024-519106-12-00

EudraCT number

2020-003432-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacogenetic

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 objectives 4

1. To evaluate the pathological downsizing and the complete resectability with neoadjuvant Alectinib.
2. To evaluate the activity of Alectinib as neo adjuvant treatment in terms of objective response.
3. To evaluate long term measures of efficacy of Alectinib as neo adjuvant and adjuvant treatment.
4. To assess the safety and tolerability profile of Alectinib as neo adjuvant and adjuvant treatment.

Conditions and MedDRA coding

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. Male or female, aged >= 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 resectable (any T with N2 , T4N0 1)
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 Tumor s (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 (mediastinal staging biopsy is allowed but not required).
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 Cockcroft Gault 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
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 t he 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 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.

Exclusion criteria 13

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 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.
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 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.
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 glucos e 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 1

1. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Viale Antonio Gramsci 14

City

Parma

Postcode

43126

Country

Italy

Scientific contact point

Organisation

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

Contact name

SCIENTIFIC STUDY COORDINATOR

Public contact point

Organisation

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

Contact name

SCIENTIFIC STUDY COORDINATOR

Locations

1 EU/EEA country · 19 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications