Table 1.
Study determinations in the AFAN study
| Study period | Selection | Treatment period | EoT | FU | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Visit | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13–23 | EoT | FU V1 | FU V2 - n |
| Weeks after visit | −4 | 0 | 1 | 2 | 4 | 8 | 12 | 16 | 20 | 24 | 28 | 32 | 36-n | * | ||
| Day 1 | −28 -to −1 | 1 | 8 (+/−2) |
15 (+/−2) |
29 (+/−2) |
57 (+/−2) |
85 (+/−2) |
113 (+/−2) |
141 (+/−2) |
169 (+/−2) |
197 (+/−2) |
225 (+/−2) |
Repeat visits 9–12 | 0–7 after last dose | 28 (+/−7) After EoT |
* (+/−7) |
| Informed consent | Prior to any study specific determination | |||||||||||||||
| Demographics, height, smoking, alcohol use | X | |||||||||||||||
| Medical record | X | |||||||||||||||
| Vital signs and body weight | X | X | X | X | X | X | X | X | X | X | X | X | X | X | ||
| Physical Exam including skin examination | X | X | X | X | X | X | X | X | X | X | X | X | X | |||
| Head and neck examination 2 | X | X | X | X | X | X | X | X | X3 | |||||||
| Tumor Imaging 3 | X | X | X | X3 | X | X4 | X | |||||||||
| ECOG Performance status | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X4 |
| Tobacco habits | X | X | X | X | X | X | X | X | X | X5 | ||||||
| 12-lead ECG | X | X | X | X | X5 | |||||||||||
| LVEF 6 | X | X | X | |||||||||||||
| Health-related quality of life 7 | X | X | X | X | X | X7 | X | X7 | X7 | |||||||
| Inclusion/exclusion criteria review | X | X8 | ||||||||||||||
| Dispensing of study medication | X | X | X | X | X | X | X | X | X | X | ||||||
| Study drug treatment 9 | Oral, continuous, once a day | |||||||||||||||
| Compliance verification 10 | X | X | X | X | X | X | X | X | X | X | X | |||||
| Adverse events | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X11 | |
| Concomitant treatment | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X12 | X12 |
| Safety laboratory tests 13 | X | X | X | X | X | X | X | X | X | X | ||||||
| Pregnancy test 14 | X | X | X | X | X | X | X | X | X | X | X | X | ||||
| Tumor tissue preservation 15 | X | X15 | X15 | |||||||||||||
| Blood and saliva samples for R + D 16 | X | X | X | X | X | X | X | X | X | |||||||
| Pharmacogenetics 17 | X | |||||||||||||||
| Vital status | X | X | ||||||||||||||
EoT: The End of Treatment visit is performed within 7 days of the last administration of study medication. If a patient permanently discontinued study medication at a scheduled visit, then the EoT visit will be conducted instead of the scheduled visit
FU V1 The first follow-up visit is performed 28 days (± 7 days) after the EoT
* FU Before Progression/SPT:
Patients ending treatment without progression should remain in the study, and should be followed up according to RECIST 1.1 every 12 weeks (approximately 3 months) until progression/SPT, initiation of new subsequent anticancer therapy, death, loss of follow-up, total patient consent withdrawal (refusing any trial procedure), or end of study (whichever occurs first). Further CT/MRI scans could be performed upon suspicion of disease progression according to standard clinical practice and physician criteria
* FU After Progression/SPT:
The following follow-up visits are conducted every 16 weeks until week 112 from Visit 2 and every 24 weeks thereafter until the end of the study. Once tumor recurrence has been radiologically confirmed, only the following data, vital status, drug-related adverse events and cancer therapy, will be obtained. At this point, scheduled visits can be replaced by telephone contacts
1 Recommended day for the visit. In the event that the visit is delayed beyond the planned schedule, it is recommended that the patient have sufficient medication during this period
2 In case of suspected tumor recurrence, it should be confirmed by imaging within 2 weeks, preferably followed by biopsy. If recurrence is not radiologically confirmed, radiological imaging should continue according to the original schedule
3 Imaging should include CT, MRI or PET-CT of the head and neck, chest and, if clinically indicated, any other site of suspected or known disease. The same radiological technique should be used throughout the study, observing the imaging guidelines. Imaging will be performed until tumor recurrence/SPT at the following times:
● Every 12 weeks (approx. 3 months) (± 1 week) until disease recurrence/SPT, loss to follow-up or unacceptable toxicity
● In the event of early discontinuation or discontinuation/delay of medication the imaging schedule should NOT be changed; patients should continue imaging according to the predefined schedule until tumor recurrence or study completion
4 Carry out until tumor recurrence/SPT
5 If not performed within the previous 8 days per standard facility procedures
6 LVEF is assessed by echocardiography/MUGA. The same procedure should be used throughout the study
7 HRQoL: EORTC QLQ-C30, EORTC QLQ-H&N-C35, and EQ-5D. Carry out every 8 weeks until tumor recurrence
8 Certain eligibility criteria are assessed at Visit 2, before study treatment administration
9 Continuous, daily treatment with Afatinib starting at Visit 2
10 After one week of treatment, compliance with treatment should be reviewed with the patient to ensure that the medication is being taken correctly. Starting at Visit 5, treatment compliance is calculated and entered into the eCRF
11After the first follow-up visit (FU V1), only drug-related adverse events are recorded
12 Information on possible concomitant treatments is collected up to FU V1. After FU V1, only information on cancer therapy is collected, if applicable
13 This includes hematology, serum biochemistry and urinalysis. Urinalysis is only performed at screening and at the EoT
14 Pregnancy testing for women of childbearing potential is mandatory prior to treatment, every 4 weeks during treatment and at EoT. If pregnancy test during selection is performed within 72 h of the first dose of study treatment, it does not need to be repeated on Visit 2
15 Biomarker analysis on preserved tissue samples is compulsory at baseline and optional at visit on week 12 and at PD. At baseline, it is required a paraffin or frozen sample of the primary tumor from the initial diagnosis (minimum 10–15 slides) and a biopsy if feasible. Samples are sent to the central laboratory for exploratory biomarker analysis only if the patient has given written informed consent to do so
16 Frequency may be modified to every 4 weeks to record changes in relevant pathological time points such as disease progression or response
17 Pharmacogenetic analysis is optional. Sample collection is only performed if the patient has given written informed consent to do so. The sample can be obtained at Visit 2 or later