Timeline, study treatment, study visits and medical procedures
| Required investigations | Screening | Day 8 (week 2) | Day 29/week 5 and every 4 weeks thereafter | Day 57/week 9 and every 8 weeks thereafter | End of study |
| Visit number | 1 | 2 | 3 | 4+ | 4+ |
| Written informed consent | Prior to screening | ||||
| Demographics (age, sex) | X | ||||
| Overall medical history | X | X | |||
| Physical examination, including weight and height | X | X | X | X | |
| Vital signs (blood pressure, pulse) | X | X | X | X | |
| ECOG/WHO performance status | X | X | X | X | |
| CT or MRI scan of measurable lesion, ≤1 month prior to start treatment | X | X | X | ||
| Haematology | X | X | X | X | |
| Serum chemistry | |||||
| Hepatic function | X | X | X | X | |
| Renal function | X | X | X | X | |
| Glucose | X | X | X | X | |
| HbA1c | X | X | X | ||
| Triglycerides | X | X | X | ||
| Cholesterol | X | X | X | ||
| Haemostatic parameters (aPTT and PT) | X | X | |||
| Insulin, IGF-1, IGF-binding protein 3 | X | X | X | ||
| Vitamin B12 | X | X | X | ||
| Metformin concentration | X | X | X | X | |
| Chloroquine concentration | X | X | X | ||
| MS of serum/urine/bile for D-2HG levels | X | X | X | X | |
| MRS for intratumoural 2HG levels | X | X | |||
| Liquid biopsy | X | X | X | X | |
| ECG | X | ||||
| Pregnancy test | X | ||||
| Optional: tumour biopsy | X | X | X |
In addition to this scheme, an ECG will be performed every 24 weeks. Metformin and chloroquine concentrations will be taken at the end of study only when possible.
aPTT, activated partial thromboplastin time; (D-)2HG, (D-)2-hydroxyglutarate; ECOG, Eastern Cooperative Oncology Group; IGF, insulin growth factor; MRS, magnetic resonance spectroscopy; MS, mass spectroscopy; PT, prothrombin time.