Download PROTOCOL #984 (DRUG 013)- Phase I Study of MK

SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
Green: Notes/Reminders that will help you fully complete the orders for your protocol
Blue: Changes you can make to customize for your study (edit, add, delete, etc.) based on your
protocol
NOTE: Throughout the orders, specify which tasks CRU nursing vs study staff are responsible for doing.
PROTOCOL #1200: Phase 1 Pharmacokinetic Study of DRUG 66 in Patients with Cancer
IRB #: STU00012435
NOTE: List PI, coordinator(s) and others who should be contacted during study visits along with
phone/pager numbers.
PI: Dr. J Jones
phone:
pager: 5-0000
Study Coordinator: S Smith
phone:
pager: 5-2222
APN or PA: G. Green
phone:
pager: 5-3333
Patients will be covered by Hem/Onc Consult Pager: 5-5119
NOTE: If there are various cohorts, arms that subjects may be in, please list this at top of Orders so it can
be checked for each of your subjects.
Coordinator specify subject consented for & collection of:
_____ PAXgene RNA
_____ PAXgene DNA
NOTE: If some subjects receive extra consents/provide extra samples, note this at the top of the Orders
so it can be checked for each of your subjects.
NOTE: You must have a set of orders for each day the subject is at CRU.
Cycle 1 Day 1 ONLY Date: ______________
Pt. Study #: _____________
1. Admit Subject to CRU as bedded outpatient/inpatient at 7:00am. Consent will have previously
been obtained by study team and supplied to CRU staff OR Consent obtained upon subject
arrival OR Page ___ at ___ to have subject consented
NOTE: The CRU must have a signed subject consent before any treatment can begin
2. Page Hem/Onc consult pager (4-5119) upon subject arrival to:
 Sign orders
 Perform H/P
 ECOG PS
 Conduct pain score
 AE assessment
NOTE: List tasks that MD completes (e.g. sign orders, H/P, AE assessment, GI/liver exam, pain
score, ECOGPS, etc.)
NOTE: The timing of when physician should be contacted/conduct H/P should be determined for
each protocol & visit. e.g., upon admission or after STAT labs results arrive
3. Physician assess if appropriate _____.
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
1
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
NOTE: If there are pre-medication requirements, note the REQUIREMENT, WHO determines if
requirement has been met, ACTION to take (e.g., Physician assess if oral hydration and
allopurinol 300 mg/day was initiated 3 days prior to visit for study to move forward)
4. Diet: General diet, prohibited foods: grapefruit juice and star fruit
NOTE: List any RESTRICTIONS (with clear definition), TIME frame for restriction, and ACTION to
take if restriction not followed (e.g., fast for 8 hours prior to study medication defined as: no
food or liquid after midnight night before. Notify coordinator if subject has not fasted so that
PK’s are not taken OR approximately 30% of calories from fat and about 50% from
carbohydrates OR Only three scheduled meals per day and one evening snack (around 8pm)
permitted and water to quench thirst. Allow 30 mins for consumption of meal. All other food
and beverage not permitted.)
5. CRU Staff to record strict I/O.
NOTE: This means that all liquid/food that enters and leaves the body is accounted for
6. Activity:_______ (bedrest, up with assistance, bathroom assistance, up ad lib as tolerated)
NOTE: If subject will be in clinic a few hours then activity orders are needed
7. CRU Staff to obtain vital signs (blood pressure, heart rate (bpm), respiration rate and oral
temperature) and record:
NOTE: What specific vitals do you want taken and recorded?
NOTE: Sitting or standing blood pressure and if sitting, 5, 10, 15 min sitting?
Contact MD if:
 Temp greater than 101
 HR greater than 100 or less than 50
 BP greater than 160/90 or less than 90/50
 RR greater than 24 or less than 12
NOTE: List CRITERIA to use to determine if there is a problem and ACTION to take if criteria met
(see example of standard criteria above)
8. CRU Staff obtain height (in/cm) and weight (lbs/kg) (w/out shoes & jacket/coat) and record on
Flow sheet.
NOTE: Clarify if measurements need to be in cm/inches or kg/lbs
NOTE: Specify if this weight will be used to determine drug dosage
9. CRU RN to insert PIL for venous blood draws.
10. CRU RN to insert second PIL in opposite arm for drug administration.
NOTE: If using a PIL for blood draws, and not employing blood sparing technique, you must add
1.5mL to each blood sampling time point to account for clearing the line prior to blood draw
NOTE: Specify if you need one line for taking blood and one for giving drug
11. If central line is in place, use for drug administration only
12. CRU Staff to collect the following labs, enter draw time, and send to NMH lab/CRU lab STAT
prior to study drug/any drug administration. Use the kit from Path Core.
NOTE: List WHERE samples to be sent, TIME frame for samples
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
2
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
BLOOD:
 ___ (number of tubes) (____ mL (volume)) ____(color of tube top) for _________
(test) – ___________ (handling instructions)
 1 (2 mL) purple top for CBC w/ differential, hemoglobin and platelet count – room
temperature
 1 (4.5 mL) light green top for creatinine clearance (send w/ urine as noted below)
 Serum pregnancy test (for women of child-bearing potential) if one was not done
within 24 hours prior to first administration of Revlimid
URINE:
 Subjects will bring 24 hour urine collection from home. Please send to NMH lab for
the following (Refrigerate during and after collection):
 24 hour urine electrophoresis
 24 hour urine immunofixation
 24 hour urine creatinine clearance (send w/ blood for creatinine clearance
[4.5mL light green top] as noted above)
NOTE: You must list number of samples, amount of sample, tube type, type of draw, and any
draw instructions (place on ice/process within 30 minutes, etc) and where to send each sample
NOTE: If a kit is to be used, the CRU must have the kit 2-3 days in advance
NOTE: List any additional clinical labs that might be needed (e.g., quantitative immunoglobulins,
creatinine clearance, etc.)
13. Page Dr. Jones, pager: 5-0000, to review lab results prior to study drug administration OR Notify
MD if:
 Absolute neutrophil count (ANC) < 1,000/μL (1.0 X 109/L)
 Pregnancy test is positive or inconclusive
NOTE: Remove this line if MD does not need to review labs
14. Study Coordinator/CRU staff will perform ECGs x3 separated at least by 10-15 mins on sponsor
provided machine
Notify MD if:
 QTC >450 ms
OR
Page NMH to perform bedside ECG x 3 ECG’s separated by at least 10-15 minutes apart
15. Study Coordinator to:
 Randomize, Assess AEs, Conmeds
 Administer Beck Depression Inventory (BDI)
 Pick up study drug from pharmacy and bring to subject’s room
NOTE: If there are several procedures that the coordinator must perform, they can be listed like
those above
16. Subject may take own meds from home while in the CRU as listed below:
(Coordinator will notify subject to bring subject’s medication in original bottles)
________________________________________
________________________________________
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
3
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
________________________________________
NOTE: MD must list meds to be taken from home, dosage, and then sign for each subject visit
NOTE: Do not list standard con meds since the list of meds taken from home should be checked
by PI/MD prior to being listed in the orders
NOTE: Subject must bring meds from home in original bottles
17. BASELINE/Pre-dose:
 Study Coordinator will perform last of 3 ECGs
 CRU Staff to obtain vital signs (sitting blood pressure, heart rate (bpm), respiration rate and
oral temperature):
Notify MD if:
 Temp greater than 101
 HR greater than 100 or less than 50
 BP greater than 160/90 or less than 90/50
 RR greater than 24 or less than 12

CRU Staff to collect the following labs, enter draw time, and send to NMH lab/CRU lab

1 (6 mL) lavender top K2-EDTA lavender tube for PK – immediately place on wet ice
NOTE: List WHERE samples to be sent, TIME frame for samples, and handling instructions (e.g.,
immediately place on wet ice OR immediately protect from light with aluminum foil OR Process
within 30 minutes OR Handle at room temperature OR Send STAT to
)
General information about PK samples:
 Tubes provided by Path Core
 Take tubes to CRU core lab for processing
 Contact Path core for pick-up and shipping
 Contact Ola Mumuney (8-0603 or lab pg 5-7619) if any problems
18. Pre-medicate subject with Dexamethazone 4 mg administered (PO or IV) prior to study drug
administration.
NOTE: Administration of drug orders should always follow this format:
Administer ____ (drug name), ____ (dose) ____ (route: PO/IV) ____(over time period)
NOTE: If administering medication while subject is on unit OR if sending medication home with
the subject, there must be a discharge item on the Orders about instructing subject on:
 What symptoms to look for and steps to take post D/C (e.g. if have temperature over
101.5, call PI)
 How to take study medications at home
19. Administer Drug 66____(dose) (PO): (May be administered without regard to meals) with water
 Dose will be based on assigned cohort
OR
Administer Drug 66 ____ (dose) as a slow intravenous bolus infusion (approx.1 mL per minute)
 Dose based on cohort that patient is assigned to
OR
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
4
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
Administer Drug 66 20 mg/m2 IV over 30 minutes using .22 micron inline filter and record exact
time given. Drug will be infused using syringe pump. CRU RN to prime IV line with study drug.
Infusion line must be flushed with a minimum of 20 mL normal saline immediately after drug
administration.
20. Record exact time study drug was administered/completed.
NOTE: Double check that you know if PK timing is to begin at START of drug or END of drug
21. Timing of PK sampling is based on when drug taken (PO)/start time of drug/end of infusion
22. Monitor subject for:
(Symptoms to look for: yellow discoloration of skin in area may result following direct contact
with the capsules)
23. If symptoms occur (e.g., discoloration), wash the exposed area with soap and water immediately
OR Call the PI immediately OR Stop the study drug OR Give rescue drug
OR
(for PRN medications to be given as needed):
 For fever >101 or headache: Tylenol 650mg PO every 4-6 hours PRN
 For nausea: Zofran 8mg IV q6-8 hrs PRN at onset of nausea
 For diarrhea: Loperamide 4mg PO, q6-8 hrs PRN after first episode.
24. DURING INFUSION:
 CRU Staff to obtain vital signs (sitting blood pressure, heart rate (bpm), respiration rate and
oral temperature):
Notify MD if:
 Temp greater than 101
 HR greater than 100 or less than 50
 BP greater than 160/90 or less than 90/50
 RR greater than 24 or less than 12
25. Post Start/END of Drug 66 Infusion:
 Study Coordinator will perform 3 ECGs
 CRU Staff to obtain vital signs (sitting blood pressure, heart rate (bpm), respiration rate and
oral temperature):
Notify MD if:
 Temp greater than 101
 HR greater than 100 or less than 50
 BP greater than 160/90 or less than 90/50
 RR greater than 24 or less than 12
.

CRU Staff collect the following, enter draw time and send to CRU lab/NMH:
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 66 PK sample – immediately
place on wet ice
 1 (4 mL) Sodium Heparin green tube for PD sample – room temperature
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
5
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 77 pre-dose PK sample –
immediately place on wet ice
NOTE: You must list number of samples, amount of sample, tube type, type of draw, and any
draw instructions (place on ice/process within 30 minutes, etc.) and where to send each sample
NOTE: If a kit is to be used, the CRU must have the kit 2-3 days in advance
NOTE: List any additional clinical labs that might be needed (e.g., quantitative immunoglobulins,
creatinine clearance)
26. CRU Staff administer flush line with 0.9 NS at 40 cc/hr for 10 minutes
27. Administer Drug 77____(dose) (PO): (May be administered without regard to meals) with water
 Dose will be based on assigned cohort
OR
Administer Drug 77_____ (dose) as a slow intravenous bolus infusion (approx.1 mL per minute)
 Dose based on cohort that patient is assigned to
OR
Administer Drug 77 20 mg/m2 IV over 15 minutes using .22 micron inline filter and record exact time
given. Drug will be infused using syringe pump. CRU RN to prime IV line with study drug. Infusion
line must be flushed with a minimum of 20 mL normal saline immediately after drug administration
28. Record exact time study drug was administered/completed.
NOTE: Double check that you know if PK timing is to begin at START of drug or END of drug.
29. 30 Minutes POST end of Drug 77 infusion:
 CRU Staff collect the following, enter draw time and send to CRU lab/NMH:

1 (6 mL) lavender top K2-EDTA lavender tube for Drug 66 PK sample –
immediately place on wet ice
NOTE: List number of samples, amount of sample, tube type, type of draw and any draw
instructions (place on ice/process within 30 minutes, etc.) and where to send each sample
NOTE: If a kit is to be used, the CRU must have the kit 2-3 days in advance
NOTE: List any additional clinical labs that might be needed (e.g., quantitative immunoglobulins,
creatinine clearance)
30. 1 HOUR POST end of Drug 66 infusion:
 CRU Staff to obtain vital signs (sitting blood pressure, heart rate (bpm), respiration rate and
oral temperature):
Notify MD if:
 Temp greater than 101
 HR greater than 100 or less than 50
 BP greater than 160/90 or less than 90/50
 RR greater than 24 or less than 12

CRU Staff collect the following, enter draw time and send to CRU lab/NMH:
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
6
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 66 PK sample – immediately
place on wet ice
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 77 PK sample – immediately
place on wet ice
NOTE: List number of samples, amount of sample, tube type, type of draw and any draw
instructions (place on ice/process within 30 minutes, etc.) and where to send each sample
NOTE: If a kit is to be used, the CRU must have the kit 2-3 days in advance
NOTE: List any additional clinical labs that might be needed (e.g., quantitative immunoglobulins,
creatinine clearance)
31. 2 HOURS POST end of Drug 66 infusion:
 CRU Staff collect the following, enter draw time and send to CRU lab/NMH:
 1 (6 mL) lavender top K2-EDTA lavender tube for Druf 66 PK sample – immediately
place on wet ice
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 77 PK sample – immediately
place on wet ice
NOTE: List number of samples, amount of sample, tube type, type of draw and any draw
instructions (place on ice/process within 30 minutes, etc.) and where to send each sample
NOTE: If a kit is to be used, the CRU must have the kit 2-3 days in advance
NOTE: List any additional clinical labs that might be needed (e.g., quantitative immunoglobulins,
creatinine clearance)
32. 4 HOURS POST end of Drug 66 infusion:
 Study Coordinator will perform of 3 ECGs
 CRU Staff to obtain vital signs (sitting blood pressure, heart rate (bpm), respiration rate and
oral temperature):
Notify MD if:
 Temp greater than 101
 HR greater than 100 or less than 50
 BP greater than 160/90 or less than 90/50
 RR greater than 24 or less than 12
.

CRU Staff collect the following, enter draw time and send to CRU lab/NMH:
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 66 PK sample – immediately
place on wet ice
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 77 PK sample – immediately
place on wet ice
NOTE: List number of samples, amount of sample, tube type, type of draw and any draw
instructions (place on ice/process within 30 minutes, etc.) and where to send each sample
NOTE: If a kit is to be used, the CRU must have the kit 2-3 days in advance
NOTE: List any additional clinical labs that might be needed (e.g., quantitative immunoglobulins,
creatinine clearance)
33. 8 HOURS POST end of Drug 66 infusion:
 CRU Staff to obtain vital signs (sitting blood pressure, heart rate (bpm), respiration rate and
oral temperature):
Notify MD if:
 Temp greater than 101
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
7
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
 HR greater than 100 or less than 50
 BP greater than 160/90 or less than 90/50
 RR greater than 24 or less than 12
.

CRU Staff collect the following, enter draw time and send to CRU lab/NMH:
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 66 PK sample – immediately
place on wet ice
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 77 PK sample – immediately
place on wet ice
NOTE: List number of samples, amount of sample, tube type, type of draw and any draw
instructions (place on ice/process within 30 minutes, etc.) and where to send each sample
NOTE: If a kit is to be used, the CRU must have the kit 2-3 days in advance
NOTE: List any additional clinical labs that might be needed (e.g., quantitative immunoglobulins,
creatinine clearance)
34. D/C PIL and discharge subject after 8 hour Post-Drug 66 dose PK and vitals are completed, if
stable
OR
If using a port-a-cath, flush line with 20 mL 0.9NS, followed by 5 mL of Heparin flush solution
(100 units/mL). Remove needle if instructed by MD to do so, or may leave in place for Day 2
infusion if properly dressed and labeled with date of needle insertion. Discharge subject after 8
hours Post Drug 66 dose PK and vitals are completed, if stable.
OR
If using any other type of central line (i.e. PICC), flush with 20 mL 0.9NS followed by 2.5 mL
Heparin flush solution (100 units/mL) and discharge subject after 8 hours Post Drug 66 dose PK
and vitals are completed, if stable.
NOTE: Choose which set of discharge orders work best. They should include: WHEN to discharge
subject
35. CRU RN/Study Coordinator to instruct subject on how to take study medication.
36. Instruct subject to notify MD immediately if the following symptoms arise:
 Fever >101.5 degrees Fahrenheit
NOTE: List any subject instructions that should be given by CRU at time of discharge.
37. Instruct subject to return to___________ on _____ (date) at _____ (time) for Day 2 procedures
and 2nd Drug 66 and Drug 77 infusion.
Page Dr. Jones, pager: 5-0000, for questions regarding study drug administration
NOTE: List PI or attending physician who should be called for questions about study
Pharmacy to send:
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
8
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
NOTE: If your protocol needs CRU Staff to administer any medications, including heparin for IV lines, they
should be listed by:
 Investigational Pharmacy
 Pre Medication
 PRN (as needed drugs on hand if side effects or problems occur)
List Drug Name, Dose route (PO/IV) over what time period.
NOTE: if administer medication while subject is on unit OR if sending medication home with the subject,
there must be a discharge item on the Orders about instructing subject on
 What symptoms to look for and steps to take post D/C (e.g. if have temperature over
101.5, call PI)
 How to take study medications at home
Investigational Pharmacy: Drug 66 and Drug 77
OR
Investigational Pharmacy: Drug 66 20mg/m2 and Drug 77 20mg/m2 infusion to be drawn into syringe
for infusion via syringe pump. CRU has syringe pump IV tubing and will prime line with drug on CRU.
Premedication:
Dexamethasone 4mg IVP
PRN:







Tylenol 650 mg PO every 4-6 hours PRN fever, headache
Zofran 8mg IV every 6-8 hours nausea
Loperamide 4mg PO every 6-8 hours diarrhea
Hydrocortisone 100 mg IV
Benadryl 25 or 50 mg IV
Epinephrine 1:1000 concentration; 0.3mg Sub Cutaneious
Demerol 25 mg. IV (if SBP >100)
Central line: 1 vial Heparin flush solution (100 units/mL)
Crash Cart on hand for emergency meds
#1200 Cycle 1 Day 1 6.2.16 MR Always put version date of draft orders and drafter’s initials
9