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

SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
Start with SAC # then complete title in 12 or 14 font
Top margin should be 2½ inches to fit the NMH Physician Order Sheet
Orders should be in 10 font.
Notes: Green used for Notes/Reminders that will help you fully complete the orders for your
protocol.
Blue: Options you can choose from for your protocol’s orders.
NOTE: Specify what tasks CRU nursing vs study staff are responsible for doing
PROTOCOL #1200 Phase 1 Pharmacokinetic Study of DRUG 66 in Patients with Cancer
NMH Research Account #: __________________
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: List PI, coordinator(s) and others who should be contacted during study visits along with
phone/pager numbers.
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 only some subjects may receive extra consents/provide extra samples, note this at the top of the
Orders so it can be checked for each of your subjects.
For Cycle 1 Day 1 ONLY Date: ______________
Pt. Study #: _____________
NOTE: need a set of orders for each day the subject is at CRU
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./Consent obtained upon subject arrival /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,
pain score and AE assessment.PRIOR to study drug administration.
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 KC 10.22.10 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 hour prior to study medication defined as: no food or liquid
after midnight night before. Notify coordinator if has not fasted so that PK’s are not taken OR e.g.,
approximately 30% of calories from Fat and about 50% from carbohydrates. E.g., 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 (sitting 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:
Standard criteria:
 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 (inches/cm) and weight (lbs/kg) (w/out shoes & jacket/coat) and record on
Flow sheet.
NOTE: clarify if want measured in cm/inches or kg/lbs.
NOTE: use this weight to determine drug dose?
9. CRU RN to insert PIL for venous blood draws.
10. 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: do 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: Kit from Path Core.
NOTE: list WHERE samples to be sent, TIME frame for samples.
BLOOD:
 1 (2 mL) purple top for CBC w/ differential, hemoglobin and platelet count. Room
Temperature
#1200 Cycle 1 Day 1 KC 10.22.10 Always put version date of draft orders and drafter’s initials
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SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
 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: must list number of samples, (amt 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 this.
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)
_____________________________________
________________________________________
________________________________________
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.
#1200 Cycle 1 Day 1 KC 10.22.10 Always put version date of draft orders and drafter’s initials
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SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
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 / Immediately protect from light with aluminum foil / Process within 30
minutes / Handle at room temperature / 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: note if time is relevant, e.g., 30-60 minute prior to….)
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
19. Administer Drug 66 ___(dose) (PO): (May be administered without regard to meals) with how
much water?
 Dose will be based on assigned cohort
OR
Administer Drug 66 ____ (dose) as a slow intravenous bolus infusion (approx.1ml per minute).
 Dose based on cohort that patient is assigned to.
OR
#1200 Cycle 1 Day 1 KC 10.22.10 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, e.g., yellow discoloration of skin in area may result following direct contact
with the capsules.)
23. If see SYMPTOM (e.g., discoloration), ACTION (e.g., Wash the exposed area with soap and water
immediately/ Call the PI immediately/ Stop the study drug/ 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 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 (4 ml) Sodium Heparin green tube for PD sample HANDLE AT ROOM TEMP
 1 (6 mL) lavender top K2-EDTA lavender tube for Drug 77 pre-dose PK sample
Immediately place on wet ice
NOTE: must list number of samples, (amt of sample) tube type, type of draw and any draw instructions
#1200 Cycle 1 Day 1 KC 10.22.10 Always put version date of draft orders and drafter’s initials
5
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
(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 how
much water?
 Dose will be based on assigned cohort
OR
Administer Drug 77 ____ (dose) as a slow intravenous bolus infusion (approx.1ml 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: must list number of samples, (amt 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:
 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: must list number of samples, (amt of sample) tube type, type of draw and any draw instructions
#1200 Cycle 1 Day 1 KC 10.22.10 Always put version date of draft orders and drafter’s initials
6
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
(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)
25.
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: must list number of samples, (amt 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. 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: must list number of samples, (amt 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)
27. 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
 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
#1200 Cycle 1 Day 1 KC 10.22.10 Always put version date of draft orders and drafter’s initials
7
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
.

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: must list number of samples, (amt 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)
28. 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 20mL 0.9NS, followed by 5mL of Heparin flush solution
(100units/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 20mL 0.9NS followed by 2.5mL
Heparin flush solution (100units/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
(after 8 hour PK dose are complete and if stable) and STEPS to take to discharge (flush line).
29. CRU RN/Study coordinator to instruct subject on how to take study medication.
30. 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.
31. Instruct subject to return to___________on (date) at (time) for Day 2 procedures and 2 nd Drug
66 and Drug 77 infusion.
Page Dr. Jones (MD) for questions regarding study drug administration, 5-2222
NOTE: List PI or Attending physician who should be called for questions about study.
Pharmacy to send:
NOTE: If your protocol needs CRU Staff to administer any medications, including heparin for IV lines, they
should be listed by:
 Investigational Pharmacy
#1200 Cycle 1 Day 1 KC 10.22.10 Always put version date of draft orders and drafter’s initials
8
SAMPLE TEMPLATE FOR COMPLEX DRUG/PK STUDY
 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 cncentration; 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 KC 10.22.10 Always put version date of draft orders and drafter’s initials
9