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Table 2 Schedule of Study Assessments and Procedures

From: Brigatinib versus other second-generation ALK inhibitors as initial treatment of anaplastic lymphoma kinase positive non-small cell lung cancer with deep phenotyping: study protocol of the ABP trial

Assessment

Screening period

Study treatment period (1st -and 2nd-line treatment, respectively) *

Follow-Up

Screening

(up to 28 days prior to D1)

Cycle 1 a

Cycle 2 a

Cycle 3 to Cycle n a

EOT b

Day / Frequency

D-28 to D0

D-14 to D0

D-7 to D0

D1

D8

D1

D1 or D15 alternating

(Q6W ±3d)

 

Q12W

±21 days

Informed consent, eligibility criteria, demographics, medical / surgical history c

X

        

Examinations

 PE e

 

X

 

X f,g

X g,m

X

X

X

 

 Height

 

X

       

 Vital signs o, Weight

  

X

X f

X

X

X

X

 

 ECG

 

X

 

Whenever clinically indicated

X

 

 ECOG Performance Status

 

X

 

X f

 

X

X

X

 

Laboratory

 Hematology p

  

X

X f

 

X

X

X

 

 Chemistry p

  

X

X f

X h

X

X

X

 

 Coagulation p

  

X

      

 Pregnancy test i

  

X

X f

Every 12 weeks (Q12W ±7 days)

X

 

 Cerebrospinal fluid (local lab)

(optional)

   

Recommended for “brain-only” progression at time of PD

  

Study treatment

 Arm A – 1st line:

Any 2nd-generation TKI

   

Dose and frequency according to current SmPC

  

 Arm B – 1st line:

Brigatinib

   

Once daily oral dose (QD p.o.)

[90 mg D1 to D7, 180 mg from D8 g,m]

  

 Arm A – 2nd line:

Any TKI

   

Dose and frequency according to current SmPC

  

 Arm B – 2nd line:

Any TKI

   

Dose and frequency according to current SmPC

  

 Diary review with patient k

   

X k

 

X

X

X

 

Continuous assessments

 Disease assessment q

X

  

Throughout study q

X q

 QoL j

  

X

Together with imaging of chest and abdomen

X

 

 AE / toxicities

   

Throughout study at every treatment day

 

 Concomitant medications

   

Throughout study

 

Biomarker sampling

 Biopsy (FFPE tumor tissue) d

X

  

After failure of first-line TKI d

After failure of second-line TKI d

  

 Blood sample collection n

  

X

Throughout study n

X

 

 Cerebrospinal fluid

   

Recommended for “brain-only” progression (at time of PD)

  

Follow-up assessments

 Survival l

        

X l

 Subsequent anticancer therapy

        

X

  1. * Second-line treatment is started after a washout period of 3 days. Choice of next-line treatment should take into account molecular results of rebiopsies. Disease assessment, including baseline imaging for the second line, must be performed within 30 days before therapy start
  2. aA cycle is defined as 28 days; acceptable window for regular visits: ±3 days, starting from cycle 2
  3. bEOT visits 30 days (±7d) after the last dose of first- and second-line treatment (30 days safety follow-up)
  4. cMedical history with details on any prior NSCLC therapy, including start and end date(s), best response(s). NOTE: Assay and sample type of prior ALK tests must be documented
  5. dExploratory biomarker studies: Central NGS-based multiplex analysis is mandatory for baseline FFPE-tissue biopsies and recommended for lesions growing under therapy
  6. eComplete physical examination (PE) at screening and EOT; symptom-directed PE at any other time point (at investigator’s discretion)
  7. fPE, ECOG performance status assessments, hematology, chemistry, and pregnancy tests are required at C1D1 (unless performed within 7 days before and no changes anticipated)
  8. gEarly pulmonary symptoms must be evaluated on C1D8 before increasing the brigatinib dose
  9. hAspartate aminotransferase / alanine aminotransaminase and total bilirubin only
  10. iPregnancy tests (urine or serum beta-human chorionic gonadotropin only, obligatory for women of childbearing potential) must be confirmed negative within 7 days before TKI start (i.e., 7 days prior to C1D1). To be repeated once every 12 weeks thereafter (every 3 cycles; Q12W ±7 days) and at EOT visit (additional testing if indicated)
  11. jQoL assessments at baseline, all tumor assessment visits (refer to footnote q), and at EOT visit (SF-12, and, in case of brain involvement, also EORTC QLQ-BN20)
  12. kPatients must document TKI intake. On C1D8, on D1 of each cycle and at the EOT visit, site staff reviews diary and crosschecks tablets or tablet bottles in the patient’s possession
  13. lSurvival follow-up shall be scheduled Q12W ± 21 days until the end of the study
  14. mPatients tolerating the brigatinib starting dose (90 mg, C1D1-D7) should increase the dose to 180 mg QD from C1D8
  15. nBlood samples at baseline (i.e., up to 7 days before TKI start) and with every CT/MRI assessment during active first- and second-line therapy (i.e. two cycles [8 weeks] after TKI start and every 12 weeks thereafter [Q12W ±7 days] (at every CT/MRI assessment visit). Samples: 2 x 7.5 ml EDTA blood and 1x 7.5 ml serum. In addition, 2 × 2.5 ml PAXgene blood for RNA isolation at four time points: i.e., (1) up to 7 days before start of first-line TKI, (2) following five cycles of first-line TKI [at the second CT/MRI assessment], (3) up to 7 days before start of second-line TKI, (4) after five cycles of second-line TKI [with CT/MRI assessment]
  16. oVital signs: body temperature, pulse, blood pressure, oxygen saturation. Special attention must be paid to blood pressure monitoring at screening and during treatment. Patients with controlled hypertension at inclusion must receive appropriate antihypertensive treatment during study participation (antihypertensive medication at the investigator's discretion, to be documented in the subject’s Concomitant Medication eCRF)
  17. pLaboratory assessments may be performed up to one day before the visit (entire study) in order to have results available on the visit day. Hematology panel: Complete Blood Cell (CBC) count with differential. Chemistry panel: albumin; alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; serum lipase, serum amylase; lactate dehydrogenase; creatine kinase; creatinine; calcium; glucose; phosphate; potassium; sodium; magnesium; total bilirubin; blood urea nitrogen or blood urea; C-reactive protein; gamma-glutamyltransferase. Coagulation: INR or PTT only at baseline
  18. qContrast-enhanced CT/MRI (chest/abdomen): all patients (unless contraindicated). Tumor response is evaluated according to RECIST 1.1 (investigator assessment). Baseline tumor evaluation at screening; response assessment according to SOC, i.e. after two cycles (8 weeks) and every 12 weeks thereafter (Q12W ±7 days) during active treatment in the first and second line. Second-line: baseline disease assessment should be performed within 30 days before TKI start. Intracranial response evaluation according to RECIST 1.1 (all patients): contrast-enhanced brain MRI/CT at screening (MRI strongly recommended). In case of brain metastasis, imaging is recommended with every scheduled assessment (intervals may be adapted depending on location and size of lesions), otherwise brain surveillance should take place according to SOC (with every second radiologic assessment). Assessments will continue until progression, death or initiation of another antineoplastic therapy after the two study treatment lines according to SOC
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BMC Cancer

ISSN: 1471-2407

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