ALEctinib for the Treatment of Pretreated RET-rearranged Advanced Non-small Cell Lung Cancer

NCT03445000 | Terminated Phase 2 Results DMC

• 3 other identifiers: ETOP 12-172017-002063-17MO30176
• Study Type: interventional
• Target: 14
• Locations: 6 countries
• Sites: 19

Brief Summary

A research study to evaluate the activity of alectinib for the Treatment of pretreated patients with advanced NSCLC that have confirmed RETrearrangement.

Conditions

Non-small Cell Lung Cancer; Non-small Cell Lung Cancer Metastatic; Non-small Cell Lung Cancer Recurrent

Keywords

RET-rearrangement; advanced NSCLC

Outcome Measures

Primary Outcomes (1)

• Best Overall Response (BOR)

  Best overall response (OR = CR or PR), per investigator assessment. OR was determined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). OR is defined as the best overall response \[Complete Response (disappearance of all target and non-target lesions, no new lesions) or Partial Response (at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of diameters, no measurable increase in a non-target lesion, no new lesions)\] across all assessment points. Radiological tumour assessments were performed using CT scans.

  Evaluated from enrollment through study completion, up to a maximum of 28 months.

Secondary Outcomes (4)

• Disease Control at 24-weeks

  From first documented response (CR, PR, SD, non-CR/non-PD) to 24 weeks or first documented progression or death from any cause, whichever came first, assessed every 8 weeks (±4 days).

• Progression-free Survival (PFS)

  Evaluated from enrollment through study completion, up to a maximum of 28 months.

• Overall Survival (OS)

  Evaluated from enrollment through study completion, up to a maximum of 28 months.

• Number of Patients Experienced Adverse Events

  Evaluated from enrollment through study completion, up to a maximum of 28 months.

Study Arms (1)

Trial treatment

EXPERIMENTAL

Alectinib is administered orally, 600 mg, twice per day (1200 mg per day) until progression, refusal or unacceptable toxicity. Trial treatment may also continue beyond progression, with physician and patient agreement, for as long as the patient may still derive clinical benefit as per investigator decision.

Drug: Alectinib

Interventions

Alectinib DRUG

Alectinib is administered orally 600mg (4x150mg capsules), twice per day (8 capsules, total 1200mg daily). The appropriate number of alectinib capsules will be provided to patients to be self-administered at home. Alectinib capsules must be taken at the same time each day with food. If a planned dose of alectinib is missed, patients can take the missed dose up until 6 hours before the next dose.

Also known as: Alecensa

Trial treatment

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented non-small cell lung carcinoma
• Advanced disease defined as recurrent stage IV (according to 8th TNM classification) or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemo-radiation therapy for locally advanced disease)
• At least one prior platinum-based systemic regimen: Adjuvant or neoadjuvant or definitive platinum-based chemo-radiotherapy treatments are considered as a line of treatment only if completed less than 6 months before enrolment. Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate regimen of therapy.
• RET rearrangement detected by FISH, Nanostring or by parallel-sequencing on FFPE tumour tissue assessed locally.
• Availability of FFPE tumour material for central confirmation of RETrearrangement
• Measurable or non-measurable, but radiologically evaluable (except for skin lesions) disease according to RECIST v1.1 criteria
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Life expectancy \>3 months
• Adequate haematological function:
• Haemoglobin ≥9 g/dL
• Neutrophil count ≥1.5 ×109/L
• Platelet count ≥100 × 109/L
• WBC ≥2 ×109/L
• Adequate renal function: Calculated creatinine clearance ≥45 mL/min (according to Cockcroft-Gault formula)

You may not qualify if:

• Untreated, active CNS metastases
• Carcinomatous meningitis
• Any previous (in the past 3 years) or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast
• Any serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes, that could affect the patient's capacity to participate in the trial
• Liver disease characterized by:
• ALT or AST \>3 × ULN (\>5 × ULN for patients with concurrent liver metastasis) confirmed on two consecutive measurements or
• Impaired excretory function (e.g., hyperbilirubinaemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminaemia, ascites, and bleeding from oesophageal varices or
• Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis
• Patients with baseline symptomatic bradycardia
• Previous treatment with any RET TKI or RET targeted therapy.
• Known EGFR, ALK, ROS, and BRAF mutation (in addition to RET rearrangement)
• Any concurrent systemic anticancer therapy.
• Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post major bowel resection.
• History of hypersensitivity to any of the additives in the alectinib drug formulation.
• Known HIV positivity or AIDS-related illness.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Hoffmann-La Roche: collaborator

Study Sites (19)

Institut Jules Bordet

Brussels, Belgium

Location

St. James Hospital

Dublin, Ireland

Location

IRCCS Instituto Tumori Giovanni Paolo II

Bari, Italy

Location

Instituto Europeo di Oncologia (IEO)

Milan, Italy

Location

University Hospital of Turin

Turin, Italy

Location

Universita di Verona

Verona, Italy

Location

The Netherlands Cancer Institute Amsterdam

Amsterdam, Netherlands

Location

University Medical Center Maastricht

Maastricht, Netherlands

Location

Hospital Teresa Herrara

A Coruña, Spain

Location

Hospital general de Alicante

Alicante, Spain

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Hospital Quirón Dexeus

Barcelona, Spain

Location

Hospital Sant Pau

Barcelona, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Regional Universitario Carlos Haya

Málaga, Spain

Location

HFR Fribourg

Fribourg, Switzerland

Location

Hôpital Universitaire de Genève

Geneva, Switzerland

Location

UniversitatSpital Zurich

Zurich, Switzerland

Location

Related Publications (5)

• Gainor JF, Shaw AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist. 2013;18(7):865-75. doi: 10.1634/theoncologist.2013-0095. Epub 2013 Jun 28.

  PMID: 23814043 RESULT

• Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012 Feb 12;18(3):378-81. doi: 10.1038/nm.2658.

  PMID: 22327623 RESULT

• Lin JJ, Kennedy E, Sequist LV, Brastianos PK, Goodwin KE, Stevens S, Wanat AC, Stober LL, Digumarthy SR, Engelman JA, Shaw AT, Gainor JF. Clinical Activity of Alectinib in Advanced RET-Rearranged Non-Small Cell Lung Cancer. J Thorac Oncol. 2016 Nov;11(11):2027-2032. doi: 10.1016/j.jtho.2016.08.126. Epub 2016 Aug 17.

  PMID: 27544060 RESULT

• Gautschi O, Milia J, Filleron T, Wolf J, Carbone DP, Owen D, Camidge R, Narayanan V, Doebele RC, Besse B, Remon-Masip J, Janne PA, Awad MM, Peled N, Byoung CC, Karp DD, Van Den Heuvel M, Wakelee HA, Neal JW, Mok TSK, Yang JCH, Ou SI, Pall G, Froesch P, Zalcman G, Gandara DR, Riess JW, Velcheti V, Zeidler K, Diebold J, Fruh M, Michels S, Monnet I, Popat S, Rosell R, Karachaliou N, Rothschild SI, Shih JY, Warth A, Muley T, Cabillic F, Mazieres J, Drilon A. Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry. J Clin Oncol. 2017 May 1;35(13):1403-1410. doi: 10.1200/JCO.2016.70.9352. Epub 2017 Mar 13.

  PMID: 28447912 RESULT

• Kodama T, Tsukaguchi T, Satoh Y, Yoshida M, Watanabe Y, Kondoh O, Sakamoto H. Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer. Mol Cancer Ther. 2014 Dec;13(12):2910-8. doi: 10.1158/1535-7163.MCT-14-0274. Epub 2014 Oct 27.

  PMID: 25349307 RESULT

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

Results Point of Contact

• Title: Heidi Roschitzki-Voser
• Organization: ETOP IBCSG Partners Foundation

ALERT-lung@etop.ibcsg.org

+41 31 511 94 00

Study Officials

• Enriqueta Felip, MD-PhD

  Vall d'Hebron University Hospital

  STUDY CHAIR

• Jürgen Wolf, MD-PhD

  University Hospital Cologne

  STUDY CHAIR

• Egbert F. Smith, MD-PhD

  The Netherlands Cancer Institute Amsterdam

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: February 26, 2018
• Study Start: November 6, 2018
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: April 8, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-03

Locations

IE (1); IT (4); BE (1); ES (8); NL (2); CH (3)