•

Synta Pharmaceuticals9090-08

Virginia Castillo

Agenda

2

1. BARC Project Team 2. Central laboratory services3. Central laboratory approach4. Material flow chart5. Trial-specific material6. Sample handling7. Shipping of samples8. Data integrity9. Reporting

BARC Project team

3

Virginia CastilloProject Manager516 719 1040vcastillo@barcusa.com

Jennifer CamejoProject Manager516 719 1052jcamejo@barcusa.com

Central lab services

•Investigator/Monitor information (manual & leaflets)

•Supplies (sampling & shipping materials)•Sample shipment•Sample analysis•Sample storage•Data management•Customized reporting•Technical support

4

Central lab approach

• LDH

• LDH isoforms

• Archived tissue/blocks

• PK

• Pharmacogenetics (PG)

• Biomarkers

Ambient shipment to BARC

Frozen shipment to BARC

5

6

Laboratory tests:

Screening Treatment Period

Within 4 Weeks of

randomiza-tion

Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle _

Day 1 (± 3 days)

Day 15 (± 3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

TESTS TO BE PERFORMED AT BARC

LDH X X X X X X X

LDH isoforms X X X X X X X

TESTS TO BE PERFORMED BY THIRD PARTY LAB

PK sampling X X

Pharmacogenet-ics (PG) sampling

X

Biomarkers X X X

Archived Tissue X

Study flow chart

7

Tests

Treatment Period

Cycle 1 Cycle 2

Day 1 (± 3 days) Day 1 (± 3 days)

prior to ganetespib

infusion termination(EOI)*

prior to docetaxel infusion

termination (EOI)*

prior to ganetespib infusion

termination (EOI)*

prior to docetaxel infusion

termination (EOI)*

TESTS TO BE PERFORMED BY THIRD PARTY LAB

PK Sampling: Arm A (Docetaxel only): X X

PK Sampling: Arm B (Ganetespib + Docetaxel): X X X X

Study flow chart – PK sampling

* EOI = End of Infusion

8

Material needed: Tests

Scr Treatment Period

Within 4 Weeks of

randomization

Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle _

Day 1 (± 3 days)

Day 15 (±

3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

Day 1 (± 3 days)

SAMPLES TO BE SHIPPED AMBIENT TO BARC

SST tube 8.5 mL (marble/brown stopper)*LDH,

LDH Isoforms 1 1 1 1 1 1 1

Large brown cap cryovial 5 mL LDH 1 1 1 1 1 1 1Clear cap cryovial 5 mL LDH Isoforms 1 1 1 1 1 1 1Red cap cryovial 5 mL (back-up)

LDH/LDH Isoforms 1 1 1 1 1 1 1

Paraffin blocks (histocassette) and/or a minimum of 10 Slides.

Archived Tissue 1

SAMPLES TO BE SHIPPED FROZEN TO BARCSodium Heparin tube 6 mL (green stopper)**

PK sampling 1 or 2 1 or 2

Blue cap cryovial 2 mL (Aliquot A) PK sampling1 or 2x2

1 or 2x2

Red cap cryovial 2 mL (Aliquot B) PK sampling1 or 2x2

1 or 2x2

K2EDTA tube 6 mL(violet stopper)

PG sampling 1Sodium Heparin tube 6 mL (green stopper)**

Biomarkers 1 1 1Orange cap cryovial 2 mL (Aliquot A)-from Sodium Heparin tube 6 mL

Biomarkers 1 1 1Violet cap cryovial 2 mL (Aliquot B)- from Sodium Heparin tube 6 mL

Biomarkers 1 1 1

K2EDTA tube 6 mL (violet stopper)** Biomarkers 1 1 1Green cap cryovial 2 mL (Aliquot A)- from K2EDTA tube 6 mL Biomarkers 1 1 1Clear cap cryovial 2 mL (Aliquot B)- from K2EDTA tube 6 mL Biomarkers 1 1 1

Trial specific material – STUDY DOCUMENTS

9

CENTRAL LAB MANUAL

• Use of Requisition Form- label sheet• Description of tests to be carried out• Supplies provided and procedure to re-order supplies through Sample

Material Request Form (SMRF) + semi automatic resupply (order proposal every 6 months)

• Sampling procedures and sample management• Transport of samples to central lab (courier contact)• Analysis and reporting• Lab accreditation certificate & reference ranges

Trial specific material – STUDY DOCUMENTS

10

INSTRUCTION LEAFLET• In local language • Summary of procedures with comprehensive pictograms (per visit)

Trial specific material – STUDY DOCUMENTS

REQUISITION FORM

• Collection of subject demographic and visit data• Identification of various samples drawn• ‘Error-proof’: all labels must be used to complete visit• Use one form per subject and per visit day• Apply barcode labels length wise• Every requisition form has a unique requisition # • Send original requisition form along with the samples to BARC.

11

To be completed per subject

Labels with unique requisition number should come here (=link between subject and requisition number used)

SHOULD BE KEPT ON SITE!

• Trial specific material – STUDY DOCUMENTS

Log of all samples taken per patient

12

SAMPLE LOG FORM

• Trial specific material – STUDY DOCUMENTS

13

SAMPLE MATERIAL REQUEST FORM

• Fill out SMRF and fax to BARC @ 516-719-1281 or email to orders@barcusa.com

• Re-supply shipping Procedure― Re-supply shipments will be shipped within 5 business

days after receipt of the order.

• Trial specific material – STUDY DOCUMENTS

14

EXAMPLE

Trial specific material – SUPPLIES

• Visit specific kits• Local handling

― Pipettes and transfer vials

• Shipment and storage material ― Pre-printed AWB, silver blue box― Ambient white Gel packs (do not freeze or referigerate)― Storage boxes (grid)

15

ALL IATA COMPLIANT

EXCLUSIVELY USE BARC SUPPLIES

Trial specific material – SUPPLIES

• INITIAL SUPPLIES

• CONTINUATION SUPPLIES• Use Sampling Material Request

Form or email at:

9090-08@barcusa.com and orders@barcusa.com

16

Sample Handling - Ambient

17

LDH AND LDH ISOFORMS

Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. The SST tube need to site in an upright position for 30 minutes after inversion and before centrifugation.

Sample Handling - Ambient

18

TUMOR TISSUE SLIDES

Sample Handling - Frozen

19

PHARMACOGENETICS (PG) SAMPLING

Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. No further processing required.

Sample Handling - Frozen

20

PK SAMPLING ARM A (DOCETAXEL)

Cycle 1/DAY 1/EOI and Cycle 2/DAY 1/EOI

Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. Centrifuge within 1 hour of sampling.

21

Sample Handling - Frozen

PK SAMPLING ARM B (GANETESPIB + DOCETAXEL)

Cycle 1/DAY 1/EOI and Cycle 2/DAY 1/EOI

Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. Centrifuge within 1 hour of sampling.

Sample Handling - Frozen

22

BIOMARKER SAMPLING

Immediately after obtaining the blood specimens, invert the tubes 8 to 10 times. Centrifuge within 1 hour of sampling.

Shipping of samples - general

• Subject is best seen in the morning to ensure timely pick-up of the samples

• Call local courier at telephone number provided by BARC within call hours (info sticker present on manual + leaflet)

• Make sure all samples in all boxes are properly labeled and original requisition form is added to box

23

Shipping of samples -general

• Courier is prepaid by BARC (BARC account number on Air Waybill)

• Ambient shipments (day of collection)• Monday through Friday

• Frozen shipments (monthly dry ice shipments)• Monday through Wednesday

• Shipments cannot be made on the day before Local Public Holidays or on Local Public Holidays.

24

Shipment of Samples – Ambient shipment

25

Shipment of Samples – Frozen shipment

26

Isothermal transport box

Gel packs stored at –20°C (or below) for at least 72 hours

Cover

Sample holder(s) with ambient samples

Airway bill Date and sign

Requisition form(s)

White storage box with frozen samples

Envelope with bubble foil

Shipment of Samples – Combined shipment

27

Data Integrity

• In order to comply with GCP, any omission or inconsistency will be

queried with a Data Clarification Form

• The DCF must be resolved promptly and returned by fax to BARC

I n d u s t r i e p a r k Z w i j n a a r d e 7 , b o x 3 , B - 9 0 5 2 G e n t , B e l g i u m

T e l . + 3 2 9 . 3 2 9 . 2 . 3 2 9 F a x + 3 2 9 . 3 2 9 . 2 . 3 3 0

A P P E N D I X V E X A M P L E D A T A C L A R I F I C A T I O N F O R M

U R G E N T T E L E F A X M E S S A G E f o r D A T A C L A R I F I C A T I O N D a t e 1 9 / 0 6 / 0 0

T o P R O F . D E M O P R O B E K L I N I K B – 1 2 3 4 T R Y O U T

A s o n t h e 1 9 / 0 6 / 0 0 , w e r e c e i v e d a s h i p m e n t f r o m P R O F . D E M O , r e l a t e d t o t h e s t u d y O r g a n o n 3 8 7 0 1 . S o m e d a t a a r e m i s s i n g o r i n c o n s i s t e n t w i t h p r e v i o u s l y o b t a i n e d d a t a . P l e a s e v e r i f y , c o m p l e t e a n d / o r c o n f i r m t h e f o l l o w i n g d a t a t h a t h a v e b e e n f i l e d i n t h e B A R C d a t a b a s e s : L a b R e f N r : 0 0 0 6 - 9 9 9 9 8 M o d i f i c a t i o n s i n t h i s c o l u m n :

P a t i e n t i d e n t i f i c a t i o n o n f i l e S u b j e c t N u m b e r : 9 9 9 9

P a t i e n t I n i t i a l s : X X X D a t e o f B i r t h : G e n d e r : F

C u r r e n t s a m p l e i d e n t i f i c a t i o n

R e q u i s i t i o n N u m b e r : 1 2 3 0 0 6 V i s i t : S C R E E N I N G D a t e o f S a m p l i n g : 1 8 / 0 6 / 0 0 H o u r o f S a m p l i n g : 0 8 : 5 4

- P l e a s e p r o v i d e t h e d a t e o f b i r t h :

V e r i f i e d b y :

T h a n k y o u f o r y o u r c o o p e r a t i o n

N a m e : D a t e : S i g n a t u r e :

P l e a s e s i g n a n d r e t u r n t h e a d a p t e d f o r m b y f a x t o + 3 2 9 . 3 2 9 . 2 . 3 3 0 A c o p y o f t h e a d a p t e d f o r m s h o u l d b e k e p t i n y o u r f i l e s .

28

Reporting

• Fax/Email reports with LDH results to site within 24 hrs after reception

• Cumulative reporting (up to two visits)• Missing results are coded: ‘N D’ « Not

done » or ‘N R’ « Not received »

29

Reporting

• Out of range values will be flagged with asterix (*) and evaluation box which needs scoring by investigator (CS/NCS)

30