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

NCT ID: NCT03445000

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-06
• Study Completion Date: 2021-03-31

Brief Summary

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

Detailed Description

The trial is investigating the efficacy of alectinib in patients with advanced stage RET-rearranged NSCLC, treated with at least one platinum based systemic chemotherapy regimen. Preclinical studies have shown that alectinib, a highly selective next generation ALK inhibitor, has potent anti-tumour activity in RET-rearranged NSCLC. Therapeutically, several multiple kinases inhibitors, are potentially able to inhibit RET kinase function, which has been tested in several unselected NCSLC trials. However, those result were negative and none of the tested drugs was approved for lung cancer treatment.

The ALERT-lung trial is a single arm, phase II trial with the primary objective to assess the efficacy of alectinib in terms of best overall response (OR) assessed by RECIST v1.1 in selected NSCLC patients with RET rearrangement. The secondary objectives are to evaluate secondary measures of clinical efficacy including disease control, progression-free survival (PFS), and overall survival (OS) as well as to assess safety and tolerability of the treatment and to describe the association of primary and secondary outcomes with tumour characteristics.

Alectinib is administered orally, 600 mg, twice 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. A total sample size of 44 patients is required.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trial treatment

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.

Group Type: EXPERIMENTAL

Alectinib

Intervention Type: 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.

Interventions

Alectinib

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.

Intervention Type: DRUG

Other Intervention Names

Alecensa

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically documented non-small cell lung carcinoma

2. 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)

3. 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.

4. RET rearrangement detected by FISH, Nanostring or by parallel-sequencing on FFPE tumour tissue assessed locally.

5. Availability of FFPE tumour material for central confirmation of RETrearrangement

6. Measurable or non-measurable, but radiologically evaluable (except for skin lesions) disease according to RECIST v1.1 criteria

7. Age ≥18 years

8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

9. Life expectancy >3 months

10. Adequate haematological function:

• Haemoglobin ≥9 g/dL
• Neutrophil count ≥1.5 ×109/L
• Platelet count ≥100 × 109/L
• WBC ≥2 ×109/L

11. Adequate renal function: Calculated creatinine clearance ≥45 mL/min (according to Cockcroft-Gault formula)

12. Adequate liver function:

• Total bilirubin ≤2x ULN (except patients with Gilbert Syndrome, who can have total bilirubin ≤3.0 mg/dL)
• ALT and AST ≤3x ULN (≤5x ULN for patients with concurrent liver ¨ metastasis)

13. Patient capable of proper therapeutic compliance, and accessible to correct followup.

14. Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine beta HCG pregnancy test within 7 days before enrolment into the trial and within 3 days before alectinib treatment start.

15. Sexually active men and women of childbearing potential must use an effective contraceptive method (intrauterine devices without hormones, bilateral tubal occlusion, vasectomized partner or total abstinence) during the trial treatment and for a period of at least 3 months following the last dose of alectinib.

16. Recovered from any previous therapy related toxicity to Grade ≤1 at date of enrolment (except for recovery to Grade ≤2 of alopecia, fatigue, creatinine increased, lack of appetite or peripheral neuropathy)

17. Written Informed Consent (IC) for trial treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention.

Exclusion Criteria

1. Untreated, active CNS metastases

2. Carcinomatous meningitis

3. 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

4. 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

5. 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

6. Patients with baseline symptomatic bradycardia

7. Previous treatment with any RET TKI or RET targeted therapy.

8. Known EGFR, ALK, ROS, and BRAF mutation (in addition to RET rearrangement)

9. Any concurrent systemic anticancer therapy.

10. Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post major bowel resection.

11. History of hypersensitivity to any of the additives in the alectinib drug formulation.

12. Known HIV positivity or AIDS-related illness.

13. Women who are pregnant or in the period of lactation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enriqueta Felip, MD-PhD

Role: STUDY_CHAIR

Vall d'Hebron University Hospital

Jürgen Wolf, MD-PhD

Role: STUDY_CHAIR

University Hospital Cologne

Egbert F. Smith, MD-PhD

Role: STUDY_CHAIR

The Netherlands Cancer Institute Amsterdam

Locations

Institut Jules Bordet

Brussels, , Belgium

St. James Hospital

Dublin, , Ireland

IRCCS Instituto Tumori Giovanni Paolo II

Bari, , Italy

Instituto Europeo di Oncologia (IEO)

Milan, , Italy

University Hospital of Turin

Turin, , Italy

Universita di Verona

Verona, , Italy

The Netherlands Cancer Institute Amsterdam

Amsterdam, , Netherlands

University Medical Center Maastricht

Maastricht, , Netherlands

Hospital Teresa Herrara

A Coruña, , Spain

Hospital general de Alicante

Alicante, , Spain

Vall d'Hebron University Hospital

Barcelona, , Spain

Hospital Quirón Dexeus

Barcelona, , Spain

Hospital Sant Pau

Barcelona, , Spain

Hospital Puerta de Hierro

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

HFR Fribourg

Fribourg, , Switzerland

Hôpital Universitaire de Genève

Geneva, , Switzerland

UniversitatSpital Zurich

Zurich, , Switzerland

Countries

Belgium; Ireland; Italy; Netherlands; Spain; Switzerland

References

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.

Reference Type: RESULT

PMID: 23814043 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22327623 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27544060 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28447912 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25349307 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002063-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO30176

Identifier Type: OTHER

Identifier Source: secondary_id

ETOP 12-17

Identifier Type: -

Identifier Source: org_study_id