Clinical Trials /

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

NCT03445000

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ALEctinib for the Treatment of Pretreated RET-rearranged Advanced Non-small Cell Lung Cancer Treatment of Pretreated RET-rearranged Advanced NSCLC
  • Official Title: A Single Arm Phase II Trial Evaluating the Activity of Alectinib for the Treatment of Pretreated RET-rearranged Advanced NSCLC

Clinical Trial IDs

  • ORG STUDY ID: ETOP 12-17
  • SECONDARY ID: 2017-002063-17
  • SECONDARY ID: MO30176
  • NCT ID: NCT03445000

Conditions

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

Interventions

DrugSynonymsArms
AlectinibAlecensaTrial treatment

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Trial treatmentExperimentalAlectinib 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.
  • Alectinib

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:Best overall response (OR = CR or PR), per investigator assessment according to RECIST 1.1.

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:Best overall response (OR = CR or PR), per independent review assessment according to RECIST 1.1.
Measure:Disease control at 24-weeks
Time Frame:24 weeks after treatment start
Safety Issue:
Description:Best overall response of CR or PR, or SD (or non-CR/non-PD in the case of non-measurable disease only)
Measure: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.
Safety Issue:
Description:PFS will be assessed according to RECIST 1.1 criteria.
Measure:Overall survival (OS)
Time Frame:From date of enrolment until date of death from any cause, assessed up to 44 months.
Safety Issue:
Description:Defined as the time from date of enrollment until death from any cause.
Measure: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.
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Thoracic Oncology Platform

Trial Keywords

  • RET-rearrangement
  • advanced NSCLC

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