Pharmacogenomic collaboration projects NSGOBMSCCKKI Resource persons

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Pharmacogenomic collaboration projectsNSGO-BMS-CC
K(KI)Resource persons

• NSGO Genomic study coordinator Elisabeth Åvall
  Lundqvist
• Coordinator BMS/CCK Nils Wilking
• CCK Suzanne Egyhazi,
• Marianne Frostvik
• BMS genomics US Peter Shaw
• BMS contact in Stockholm Ann-Louice Bruhn
• NSGO datacenter Odense Gerda Andersen
• CTU genomic resource Stockholm Anne Brandt

EÅL 040423
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Pharmacogenomics - Objectives

• To explore the relationship of gene variants and
  gene expression patterns to treatment response
• Microarray analysis of 30 000 genes
• Build up an NSGO biobank at CCK for future
  pharmacogenomic research
• Serum proteomics
• Single Nucleotide Polymorphism (SNP)
  relationship to toxicity

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GCIG Intergroup trial (NSGO-OC-0102, AGO-OVAR9,
GINECO)

• NSGO Genomic substudy
• Projected accrual N150
• Opened April, 2003
• Participating sites
• Stockholm (SE)
• Umeå (SE)
• Karlstad (SE)
• Linköping (SE)
• Oslo (N)
• Will be prolonged

• Clinical study
• Projected accrual N 1716
• Opened July, 2002
• NSGO opened Oct.2002
• Closed for inclusion April 23, 2004

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NSGO-OC-0102 Recruitment (until April 19, 2004)
Excluded. Not included in clinical study
(endometrial cancer)
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NSGO-OC-0102 Stockholm RNA content (tot µg)
in tissue
Aim RNA content at least 2 µg
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Pharmacogenomic substudy to NSGO-OC-0102
Recruitment Stockholm until April 23, 2004

• N
• Screened 77
• Randomized 26
• Pharmacogenomic 9
• Blood 9
• Tissue 9
• Tissue collected from 31 pts-
• only 9 of them met eligibility
• criteria for clinical study.
• Pts for pharmacogenomics
• only recruited from Karolinska.

• Non-participants
• Clinical study
• N
• Refusal 13
• Excl.criteria 22
• Admin.cause 16 51
• Late referral after surgery, lack of
• time to radiology, treatment time etc.

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Pharmacogenomic substudy to NSGO-OC-0102

• Will continue for
• Patients with stage IIB-IV ovarian, peritoneal,
  fallopian tube
• Treated with standard paclitaxel-carboplatin
• Amendment I April 26, 2004
• Send Amendment to IEC
• Heparin blood sample replaced by serum
• Blood samples obtained prior to surgery
• Call NSGO datacenter for registration number
• CRF will be revised
• Interested?

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Pharmacogenomic substudy to NSGO-OC-0102 - Schema

• At planning of a routine primary surgical
  procedure for
• verification of primary cancer in the ovary,
  fallopian tube or peritoneum
• Obtain consent for pharmacogenomic study
• Obtain blood samples (EDTA and serum)
• fill in worksheet (3 copies)
• Perform routine primary surgical procedure
• Obtain tumor sample (biopsy/FNA/ascites) for
  pharmacogenomics
• Important! Transportation of tumor from surgery
  ward to pathologist should be performed on ice
  and directly after the tumor has been removed.
  Immediately immerse biopsy/FNA in a tube with
  RNAlater? after pathologist selected
  representative material.

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Pharmacogenomic substudy to NSGO-OC-0102 Schema
cont.

• Check eligibility
• (i.e Stage IIB-IV, standardtreatment with
  paclitaxel-carboplatin)
• Call NSGO datacenter in Odense for registration
  number
• Keep tumor sample and EDTA blood at 4 oC until
  shipment to
• CCK, Karolinska Institute, preferably within 24
  hours
• of collection (if not possible, store it at 4oC
  until shipped)
• Call World Courier for shipment. Alert CCK the
  day of shipment
• Proceed with standardtreatment with
  paclitaxel-carboplatin
• Fill in adjusted CRF and send to NSGO datacenter
  in Odense.
• Store frozen serum at -70 oC. Shipment to CCK
  twice early
• In case of withdrawal (ineligibility, pts
  request) fill in Withdrawal form

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NSGO-OC-0101 - Reciststudy

• Clinical study
• Pharmacogenomic study
• Blood
• Tissue (FNA/ascites/biopsy)
• Angiogenesis study

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NSGO-OC-0101- Reciststudy

• NSGO Genomic substudy
• Projected accrual N100
• Opened Oct, 2002

• Clinical study
• Projected accrual N 250
• Opened June, 2002
• Projected recruitment-period 36 months

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NSGO-OC-0101

• Pharmacogenomics
• participating sites
• Sweden
• Stockholm, Umeå, Karlstad
• Linköping, Karlstad, Falun, Gävle
• Norway
• Oslo
• Finland
• Turku

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NSGO-OC-0101 - recruitment
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Reciststudy Recruitment in Stockholm

• N
• Screened 47
• Randomized 24
• Pharmacogenomic 15
• Blood 15
• Tissue 7 ( one FNA with no tumor)
• Angiogenesis 21
• Non-participants clinical study
• Refusal 9
• Admin.cause 1
• Exclus.criteria 6
• Pts preferal of treatm. 7

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NSGO-OC-0102 Stockholm RNA content (tot µg) in
tissue
Aim RNA content at least 2 µg
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Study schematic

• Confirm eligibility in clinical Reciststudy
• Obtain consent for clinical and pharmacogenomic
  study
• Obtain the blood (EDTA and serum)
• and tissue sample (FNA/ascites)
• fill in worksheet (3 copies)
• Call World Courier for shipment. Alert CCK the
  day of shipment!
• Keep tumor sample and EDTA blood at 40C until
  shipment,
• preferably within 24 hours
• Store frozen serum at -700C (-200C). Shipment to
  CCK twice yearly

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Collection of FNA

• Study nurse provide genomic tissue sample kit
  tissue sample worksheet to the physician
• Unique Tissue Identification number (TIN) inside
  Nasco bag must be written on worksheet
• Perform FNA swipe microscope slides with the
  instrument. Lable the slide with unique TIN.
  Airdry.Cytologist check for tumor
  representativity.
• Immediately press out content in syringe into a
  tube and fill it up with RNA later.
• Complete worksheet. Keep one copy and place two
  copies in the bag.
• Place the bag in a refrigerator at 40C. DO NOT
  FREEZE
• Multiple FNA are recommended! Each FNA should
  have its own unique TIN and separate worksheet.

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Collection of ascites

• Study nurse provide genomic tissue sample kit and
  two sterile 50ml tubes tissue sample worksheet
  to the physician
• Unique Tissue Identification number (TIN) inside
  Nasco bag must be written on worksheet
• Fill up the two tubes with ascites. Put the tubes
  into the Nasco bag. DO NOT ADD RNA later.
• Complete worksheet. Keep one copy and place two
  copies in the bag.
• Place the bag in a refrigerator at 40C. DO NOT
  FREEZE.
• The whole procedure for FNA and ascites should
  not take more than 5-10 minutes.
• Each site must inform CCK, by fax, about
  randomization number

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Logistics Site CCK NSGO - BMS
Site
Sampling fill in worksheet (WS) Retain one copy
of worksheet Send samples2 copies (WS) to CCK
NSGO datacenter Odense
CCK
Receives original WS Documents WS in
database Delivers clinical data to BMS through
TIN
Registrates samples Retain one copy WS Sends
DNARNA to BMS by TIN Administrates
Biobank Receives results from BMS
Analysis of samples Delivers results to CCK No
biobanking at BMS
BMS