Part 2, I don't know the significence of all the "X" symbols maybe onc talk. Did I mention my onc told me to go easy on him, have know idea what he means, tongue in cheek! But I will be asking a lot of questions.
Love & Hugs Lyn
Efficacy Assessments
1. Objective responses. Tumour lesions will be assessed clinically or radiologically (CT or MRI scans), and measurable lesions will be quantified using the RECIST criteria. Evaluation for responses will be made by repeating clinical measurements after each cycle of CYT997 and repeating scans after every second cycle.
2. Vascular-targeting activity. The effects of CYT997 on tumour vasculature will be evaluated using the techniques listed below:
(i) Dynamic contrast-enhanced MRI (DCE-MRI) scans of tumour lesions will be performed before and after the first infusion of CYT997.
(ii) Measurement of viable and apoptotic circulating endothelial cells by flow cytometry will be performed at 0, 8 and 24 hours from starting the first CYT997 infusion.
(iii) Assay of the serotonin metabolite 5-HIAA in blood will be performed before and after the first CYT997 infusion.
(iv) Re-biopsy of tumour lesions one week after the first CYT997 infusion will be performed in patients with accessible tumours (eg., cutaneous or nodal metastases) who give specific informed consent. Samples will be assessed histologically for apoptosis, necrosis and changes in tumour microvasculature.
8. STUDY CALENDAR
Baseline evaluations are to be conducted within 1 week prior to start of protocol therapy. Scans and x-rays must be done within 4 weeks prior to the start of therapy.
Pre-
study
Wk 12
Wk
2
Wk
3
Wk
4
Wk
5
Wk
6
Wk
7
Wk
8
Wk
9
Cycles
4-6
Off
study
Pre-inf
8 hr
24 hr
48 hr
72 hr
96 hr
CYT9971
X
X
X
X
Informed consent
X
Demographics/Medical history
X
Concurrent medications
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X-----------------------X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
Urinalysis3
X
X-----------------------X
X
X
X
X
X
X
Performance status
X
X
X
X
X
X
Full blood count
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation profile4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Plasma biochemistry5
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum pregnancy test6
X
Pharmacokinetic samples7
X-----------------------------------------X
Samples for biological endpoints8
X-----------------------X
X
X
DCE-MRI9
X
X
X
Adverse event evaluation
X--------------------------------------------------------------------------------------------------------------------------------X
X
Tumour measurements
X
Tumour measurements are repeated after every 2nd cycle of CYT997
X10
Radiological evaluation
X
Radiological measurements are performed after every 2nd cycle of CYT997
X10
ECG
X
X
X
X
X
X
X
X
X
X
Gated heart pool scan
X
X
X11
Pulmonary function tests12
X
X
X11
1. Dose as assigned; 24-hour continuous IV infusion
2. Assessments to be performed prior to commencing the CYT997 infusion and at 8, 24, 48, 72 and 96 hours after the start of the infusion
3. Dipstick test; urine microscopy/culture and 24-hour urine protein if abnormal (greater than 1+ of blood or protein)
4. PT, APTT and fibrinogen
5. Electrolytes, bicarbonate, glucose, urea, creatinine, urate, albumin, total bilirubin, alkaline phosphatase, AST, ALT, LDH, calcium and phosphate
6. Women of childbearing potential
7. Blood and urine samples (see Section 7.3)
8. See Section 7.1
9. Dynamic contrast-enhanced MRI scan (see Section 7.2)
10. Two consecutive measurements taken 4 weeks apart must be used to document progressive disease if the patient is removed from study for this reason.
11. Prior to every 2nd cycle of CYT997
12. Spirometry, lung volumes and diffusing capacity