ELEVATE – evaluating Temozolomide and Nivolumab in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma with MGMT methylation: study protocol for a single arm phase II trial

Table 1 Schedule of observations and procedures (SPIRIT figure for ELEVATE – Additional file 4)

Visit:	Pre-Screen	Screening (within 28 days of C1)	Baseline (D1 C1 TMZ – 28 day cycle)	Day 1 of each TMZ cycle	Progression or cessation of TMZ or at month 3/day 84 (+/- 7 days)	Day 1 of each Nivo (+/- TMZ) cycle	Progression/End of treatment
Informed consent - Tumour analysis for MGMT methylation	X
Archival tumour tissue to central laboratory	X
Informed Consent		X
Eligibility Evaluation		X
Medical History		X
Mismatch repair proficient testing (MSI-normal or MMR intact)		X
Physical Exam^a		X	X	X	X	X	X
Vital signs^b		X	X	X	X	X	X
ECOG performance Status		X	X	X	X	X	X
Phone call to check compliance				X		X
Echo/MUGA^c		X
Pregnancy test in WOCBP		X	X	X		X
CT Scan^d		X		X^e	X^f	X^g
Serum Chemistry (U&E^h, LFTSⁱ,CalciumCA19-9)		X	X	X	X	X	X
Endocrine tests: Morning cortisol, ACTH, TSH (Free T3 and Free T4 in case of abnormal TSH)		X				X^j
Full blood count		X	X^k	X^k	X	X^k
Serology – HBV or HCV		X
ECG^l		X
Adverse Events		X	X	X	X	X	X
Concomitant Medication		X^m	X	X	X	X	X
Patient registered with NHS Digital			X
Quality of Life Questionnairesⁿ			X	X	X	X	X
Details of next treatment							X
TRANSLATIONAL SAMPLES
Tumour Biopsy (endoscopy)					X		X^o
Translational blood (ctDNA, Plasma)		X	X	X^p	X	X^q	X

^aHeight and weight. Height only required at screening
^bTemperature, blood pressure, heart rate, respiratory rate, oxygen saturation
^cIf clinically indicated
^dAssessments performed following RECIST 1.1/iRECIST guidelines as appropriate)
^eCT scans are required at week 6 and week 12 of TMZ treatment. Assessment of scan should be completed following RECIST 1.1 guidelines
^fCT scan not required if cessation of TMZ occurs within 4 weeks of the week 6 scan
^gCT scan at week 6 and week 12 of Nivolumab treatment and then every 12 weeks thereafter until CT scan demonstrates unconfirmed progression, following iRECIST guidelines, then a confirmatory CT scan should be performed 4-6 weeks later
^hUrea and electrolytes
ⁱAST and/or ALT, ALP, bilirubin
^jEvery 6 weeks on nivolumab (TSH, cortisol)
^kFBC weekly whilst on TMZ
^lWithin 7 days prior to treatment start date
^mTo include all those being taken from 30 days prior to starting trial treatment and during treatment and up to 100 days after last study dose
ⁿEORTC QLQ-C30, EQ-5D-5L & QLQ-OG25
^oOptional endoscopy
^pAt 4-6 weeks from D1 C1 TMZ
^qAt 4-6 weeks from D1 C1 Nivolumab

ISSN: 1471-2407