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ALEctinib for the Treatment of Pretreated RET-rearranged Advanced Non-small Cell Lung Cancer (ALERT-lung)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03445000
Recruitment Status : Recruiting
First Posted : February 26, 2018
Last Update Posted : August 21, 2019
Hoffmann-La Roche
Information provided by (Responsible Party):
European Thoracic Oncology Platform

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

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Non-small Cell Lung Cancer Metastatic Non-small Cell Lung Cancer Recurrent Drug: Alectinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm Phase II Trial Evaluating the Activity of Alectinib for the Treatment of Pretreated RET-rearranged Advanced NSCLC
Actual Study Start Date : November 6, 2018
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Alectinib

Arm Intervention/treatment
Experimental: 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.

Drug: 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.

Other Name: Alecensa

Primary Outcome Measures :
  1. Best overall response [ Time Frame: From the start of trial treatment across all time points until the end of trial treatment, assssed up to 44 months. ]
    Best overall response (OR = CR or PR), per investigator assessment according to RECIST 1.1.

Secondary Outcome Measures :
  1. Best overall response per independent review [ Time Frame: From the start of trial treatment across all time points until the end of trial treatment, assssed up to 44 months. ]
    Best overall response (OR = CR or PR), per independent review assessment according to RECIST 1.1.

  2. Disease control at 24-weeks [ Time Frame: 24 weeks after treatment start ]
    Best overall response of CR or PR, or SD (or non-CR/non-PD in the case of non-measurable disease only)

  3. Progression-free survival (PFS) [ Time Frame: From date of enrolment until date of documented progression or death, if progression is not documented, assessed up to 44 months. ]
    PFS will be assessed according to RECIST 1.1 criteria.

  4. Overall survival (OS) [ Time Frame: From date of enrolment until date of death from any cause, assessed up to 44 months. ]
    Defined as the time from date of enrollment until death from any cause.

  5. Safety and tolerability of alectinib treatment [ Time Frame: Assessed from date of signature of informed consent until 30 days after treatment is ceased for any reason. ]
    The safety and tolerability of alectinib treatment will be assessed through analysis of the worst grade of toxicity/adverse events according to CTCAE v4.0 criteria observed over the whole treatment period.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03445000

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Contact: Barbara Ruepp, PharmD +41315119416

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Institut Jules Bordet Recruiting
Brussels, Belgium
Principal Investigator: Thierry Berghmans         
Unicancer - Institut Bergonie Not yet recruiting
Bordeaux, France
Principal Investigator: Sophie Cousin         
Hospital Nord Not yet recruiting
Marseille, France
Principal Investigator: Laurent Greillier         
Gustave Roussy Not yet recruiting
Villejuif, France
Principal Investigator: Benjamin Besse         
St. James Hospital Recruiting
Dublin, Ireland
Principal Investigator: Sinead Cuffe         
IRCCS Instituto Tumori Giovanni Paolo II Recruiting
Bari, Italy
Principal Investigator: Domenico Galetta         
Instituto Europeo di Oncologia (IEO) Recruiting
Milano, Italy
Principal Investigator: Filippo de Marinis         
University Hospital of Turin Recruiting
Turin, Italy
Principal Investigator: Silvia Novello         
Universita di Verona Recruiting
Verona, Italy
Principal Investigator: Emilio Bria         
The Netherlands Cancer Institute Amsterdam Recruiting
Amsterdam, Netherlands
Principal Investigator: Egbert Smith         
University Medical Center Maastricht Not yet recruiting
Maastricht, Netherlands
Principal Investigator: Anne-Marie Dingemans         
IPO Porto Not yet recruiting
Porto, Portugal
Principal Investigator: Júlio Oliveira         
University Clinic Golnik Not yet recruiting
Golnik, Slovenia, 4204
Principal Investigator: Katja Mohorčič         
Institute of Oncology Not yet recruiting
Ljubljana, Slovenia, 1000
Principal Investigator: Nina Turnšek Hitij         
Hospital general de Alicante Recruiting
Alicante, Spain
Principal Investigator: Bartomeu Massutí         
Vall d'Hebron University Hospital Recruiting
Barcelona, Spain, 08035
Principal Investigator: Enriqueta Felip, M.D.         
Hospital Quirón Dexeus Recruiting
Barcelona, Spain
Principal Investigator: Santiago Viteri         
Hospital Sant Pau Recruiting
Barcelona, Spain
Principal Investigator: Ivana Sullivan         
Hospital Teresa Herrara Recruiting
La Coruna, Spain
Contact: Rosario Garcia Campelo, MD   
Hospital Puerta de Hierro Recruiting
Madrid, Spain
Contact: Mariano Provencio, MD   
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Principal Investigator: Luis Paz Ares         
Hospital Regional Universitario Carlos Haya Recruiting
Málaga, Spain
Principal Investigator: Manuel Cobo         
HFR Fribourg Recruiting
Fribourg, Switzerland
Principal Investigator: Daniel Betticher         
Hôpital Universitaire de Genève Recruiting
Genève, Switzerland
Principal Investigator: Alfredo Addeo         
UniversitatSpital Zurich Recruiting
Zurich, Switzerland
Contact: Christian Britschgi, MD   
Principal Investigator: Christian Britschgi, MD         
Sponsors and Collaborators
European Thoracic Oncology Platform
Hoffmann-La Roche
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Study Chair: 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

Publications of Results:

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Responsible Party: European Thoracic Oncology Platform Identifier: NCT03445000     History of Changes
Other Study ID Numbers: ETOP 12-17
2017-002063-17 ( EudraCT Number )
MO30176 ( Other Identifier: Roche )
First Posted: February 26, 2018    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Thoracic Oncology Platform:
advanced NSCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms