Table 2.
Study calendar
| Screening for eligibility | ||
| Within 4 weeks prior to enrolment | ▸ Clinical Assessment* ▸ 24 h urine collection for urine protein, urine creatinine and urine albumin ▸ Serum creatinine ▸ Glycated haemoglobin ▸ HIV antibody ▸ Radiological evaluations† ▸ Histopathological confirmation of progressive, low-grade or intermediate-grade NET |
|
| Within 2 weeks prior to enrolment | ▸ 12-lead ECG‡ ▸ CBC§A, chemistries§B, INR, lipid panel (fasting) |
|
| Within 3 days prior to enrolment | ▸ Serum or urine HCG (in women of childbearing potential only) | |
| Enrolment |
Patient signs consent | |
|---|---|---|
| Prior to treatment with study drug | ||
| (surgical candidates only) Month –3 to Day 1 |
▸ Contrast enhanced CT scan (within 4 weeks prior to operation—screening scan may be used if timeframe is met) ▸ Standard preoperative evaluation based on diagnosis ▸ Cytoreductive surgery and intraoperative biospecimen collection for gentotyping ▸ Contrast enhanced CT scan for postoperative tumour burden (within 4 weeks prior to study drug initiation) ▸ Routine postsurgery care and recovery |
|
| (Patients not undergoing surgery only) Month –3 to Day 1 |
▸ Image-guided tumour biopsy for genotyping | |
| All patients Within 4 weeks prior to treatment initiation |
▸ Hepatitis B and C evaluation ▸ Echocardiogram (in patients with carcinoid tumours only) |
|
| All patients Within 2 weeks prior to treatment initiation (Tests need not be repeated if they have been done during the appropriate timeframe at screening) |
▸ Clinical assessment* ▸ Chromogranin A, pancreatic polypeptide, and neuron-specific enolase. ▸ Vasoactive intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin, fasting insulin, C-peptide (proinsulin) and/or glucagon only in patients known to have functioning NETs. ▸ CBC§A, chemistries§B, and TFTs§C ▸ Urinalysis ▸ Cardiac evaluation (in patients that present with cardiac or pulmonary risk factors) ▸ CT CAP or MRI†¶ ▸ 12-lead ECG‡ ▸ 30 mL of peripheral blood f (red top tubes) or research (see section error! Reference source not found) |
|
| Women of childbearing potential only Within 3 days of study drug initiation |
▸ Urine or serum HCG | |
| Treatment based on tumour genotyping | ||
| Cycle 1 (28 days) | Day 14 | ▸ Clinical assessment* ▸ CBC§A and chemistries§B, ▸ Urinalysis |
| Cycle 2 (28 days) | Day 1 | ▸ Clinical assessment* ▸ CBC§A, chemistries§B, and TFTs§C ▸ Urine or serum HCG in women of childbearing potential ▸ Urinalysis ▸ 12-lead ECG‡ |
| Day 14 | ▸ CBC§A, ▸ Chemistries§B, ▸ Urinalysis |
|
| Cycle N (28 days) | Day 1 | ▸ Clinical assessment* ▸ CBC§A, chemistries§B, and TFTs§C ▸ Urine or serum HCG in women of childbearing potential ▸ Urinalysis ▸ 12-lead ECG‡ ▸ Radiological evaluation of treatment response¶ |
| Final/early termination visit** | ▸ Clinical assessment* ▸ CBC§A, chemistries§B, and TFTs§C ▸ Urine or serum HCG in women of childbearing potential ▸ Urinalysis ▸ Radiological evaluation of treatment response¶ (not applicable for patients that have progressed on 2 drugs) |
|
| Long term follow-up | Telephone contact every 3 months to determine anticancer therapy and survival status | |
| Concomitant medications | Throughout study | |
| AEs | Throughout study | |
*Clinical assessment: complete history and physical examination including height, weight, vital signs (including blood pressure, pulse) and ECOG at screening, baseline, days 1 and 15 of cycle 1, and then on day 1 of each subsequent cycle. 12-Lead ECG to be completed within 2 weeks prior to treatment and then at the end of each cycle prior to starting next cycle of therapy.
†Radiological evaluations to be completed as part of the screening.
▸ Brain MRI or CT.
▸ Contrast CT scan or MRI of the chest, abdomen and pelvis (CT C/A/P) for the purpose of tumour burden and tumour volumetric measurement.
▸ Bone scan for patients in whom bone metastases are suspected.
▸ FDG PET scan.
‡12 Lead ECG to be completed within 2 weeks prior to treatment and then at the end of each cycle prior to starting next cycle of therapy.
§Laboratory evaluations:
A. CBC with differential and platelets to be completed within 2 weeks prior to enrolment, within 2 weeks prior to treatment, then every 2 weeks for the first 2 cycles and then every 4 weeks thereafter.
B. Chemistries: sodium (Na), potassium (K), chloride (Cl), total CO2 (bicarbonate), creatinine, glucose, urea nitrogen (BUN), albumin, calcium total, alkaline phosphatase, ALT/GPT, AST/GOT, total bilirubin, total protein to be completed within 2 weeks prior to enrolment, within 2 weeks prior to treatment, then every 2 weeks for the first 2 cycles and then every 4 weeks thereafter.
C. TFTs: Free T3, TSH to be done within 2 weeks prior to treatment then every 4 weeks thereafter.
¶A CT or MRI of the chest/abdomen/pelvis to reassess treatment response will be done at baseline, at 3 months after treatment initiation and then every 3 months. MRI can be substituted for CT scan at the discretion of the investigator as some lesions such as hepatic metastasis are best visualised on MRI.
**Final/early termination visit will occur approximately 30 days after the last dose of study drug.
AEs, adverse events; CBC, complete blood count; ECOG, Eastern Cooperative Oncology Group; FDG, Fluorodeoxyglucose; HCG, human chorionic gonadotropin; INR, international normalised ratio; NET, neuroendocrine tumour; PET, positron emission tomography; TFTs, Thyroid function tests; TSH, thyroid-stimulating hormone.