Pathology and Correlative Science Instructions for NSABP Foundation Protocol FB-11

Transcription

1 Pathology and Correlative Science Instructions for NSABP Foundation Protocol FB-11 A Phase II Randomized Study Evaluating the Biological and Clinical Effects of the Combination of Palbociclib with Letrozole as Neoadjuvant Therapy in Post-Menopausal Women with Estrogen-Receptor Positive Primary Breast Cancer Version Date: May 20, 2015

2 NSABP FOUNDATION FB-11 PATHOLOGY AND CORRELATIVE SCIENCE INSTRUCTIONS Instructions for Use and Distribution of the : The NSABP FB-11 Pathology and Correlative Science Instructions provide essential information to support the correlative science studies described in Section 6.0 of the FB-11 protocol. These instructions should be distributed to staff involved with any aspect of sample collection and submission, including staff at satellite institutions. Special Notes for the FB-11 Study: Collection and submission of the following tumor and blood samples are required for all patients. Non-submission of the required samples will be considered a protocol violation. A minimum of 2 and a maximum of 4 core-cut biopsies from each patient at baseline, after 2 weeks of study therapy and upon completion of study therapy at 14 weeks. If gross residual disease 1.0 cm remains at the time of definitive breast surgery (following completion of neoadjuvant therapy), tumor samples (fresh tissue) will be collected from the residual disease specimen. Blood sample collections: at baseline, after 2 weeks of study therapy and upon completion of study therapy at 14 weeks. Collection and submission of the following tumor and blood specimens are required only for patients who agree to these optional procedures. (See study treatment and optional tumor collection consent forms.) Patients who stop therapy before 14 weeks, and have received at least 1 cycle (4 weeks) of study therapy, will be asked permission for core biopsies and blood samples at the time study therapy is stopped. Table of Contents: 1.0 Kit instructions (FB-11 fresh tissue core biopsies and blood samples) Kit contents (fresh tissue equipment) Kit contents (blood sample tubes collection equipment) Sample collection and submission instructions (fresh tissue core biopsies and blood samples) 2.1 General sample collection and kit preparation instructions Blood sample collection and submission instructions Fresh tumor core biopsy collection and submission instructions Preparation of fresh tumor tissue and blood samples for shipping Patient withdrawal of permission for use of specimens. 9 Page 1 of 9

3 1.0 Kit instructions (FB-11 fresh tissue core biopsies and blood samples) Patients affected All FB-11 patients Obtaining kits for core biopsies and blood specimen samples FB-11 Patient ID Numbers to be used for fresh tissue and blood samples FB-11 Sample submission kits When the first patient is being screened, the Protocol FB-11 Specimen Kit Request to the NSABP Department of Site and Study Management (DSSM) at The Baseline kit will be shipped to the main member site. Subsequent kits (Week 2 and Week 14/Optional) will be shipped to the site upon receipt of the previous kit. A separate kit request is to be made for the collection of gross residual disease 1cm. the Protocol FB-11 Specimen Kit Request to DSSM once the surgery has been scheduled. For requests received before 2 PM (ET), kits will be sent to arrive in 3 business days (allow 1 additional business day for requests made after 2PM [ET]). When scheduling the biopsy, allow enough time to receive the kit and distribute to a satellite if necessary. Upon entry of patient information into the MARVIN EDC system, an FB-11 Patient ID Number will be assigned and must be used for all FB-11 blood and tumor specimens. The FB-11 Patient ID Number must be recorded on submitted samples and included on Forms: Baseline, Week 2, Week 14, and surgical tumor sample (if applicable) in the FB-11 Specimen Tracking System (STS), which will be printed and submitted with the samples. For questions, please contact DSSM by phone ( ) or (industry.trials@nsabp.org). Following are the contents of each fresh tumor tissue and blood sample collection and submission kit. Maintain contents in kit until use. Outside carton: 1. Shipping label Inside top lid: 1. Vinyl cover with "UN3373" label affixed 2. Inside vinyl cover: a. Collection and shipping instructions b. "UN1845" Dry Ice label c. List of kit contents d. Prepaid Air Bill and clear mailer sleeve Lower chamber: 1. 6 x 9 Biohazard specimen bag with absorbent pad, temp tag, and "Frozen Specimen" label gauge sterile core biopsy gun Top tray: 1. Marking pen 2. One 8.5 ml PAXgene DNA tube with resealable bag 3. One 10 ml EDTA (lavender top) blood tube 4. Four nunc cryo-tubes 5. Phlebotomy kit Tourniquet Vacutainer sleeve 21 gauge needle Two alcohol pads 4x4 gauze pad Bandage 6. Cryo kit Two cryo-molds Two cryo-cassettes 7. Freeze plate 8. Two 2 x 3 frozen specimen bags ml OCT syringe ml sterile pipette 11. Forceps 12. Transport canister with foam insert 13. Two 10% neutral buffered formalin tubes in resealable bags (retain for shipping) For questions related to kit contents or blood specimens, contact pathology.questions@nsabp.org or Questions re: kits Page 2 of 9

4 Kit instructions (continued) 1.1 Kit contents (Fresh tissue equipment) Steel freezing plate (10cm x 77.6cm) 2 x collection tubes with formalin (10% neutral buffered formal-saline) 2 x TissueTek cryo-molds (2.4cm x 2cm) OCT solution in syringe 2 x cryo-cassettes 14 gauge biopsy needle Page 3 of 9

5 Kit instructions (continued) 1.2 Kit contents (blood sample tubes collection equipment) 8.5ml PAXgene DNA tube 1 x 10ml EDTA tube 4 x 1.8ml nunc cryo-tubes 21 gauge needle with vacutainer sleeve Aluminum transport container for fresh tumor biopsy(ies) in 10% Formalin collection tubes and PAXgene DNA blood tube. Page 4 of 9

6 2.0 Sample collection and submission instructions (fresh tissue core biopsies and blood samples) 2.1 General sample collection and kit preparation instructions Considerations for timing of sample collections and kit preparation After the consent form has been signed, the patient has given permission for the blood and tumor biopsy(ies), and eligibility screening has been completed but before enrollment, schedule the baseline biopsy procedure (Monday through Thursday). Baseline, Week 2, and Week 14 biopsies must be scheduled on a day that will allow the fresh tissue samples to be received by the NSABP Division of Pathology on a business day (e.g., do not ship samples on Friday or on the day before a holiday). Note: Enrollment may occur on the same day as the baseline biopsy; however, the baseline fresh tumor and blood samples must be procured before the patient is enrolled. Before the blood samples are collected and the core biopsy(s) are performed, remove and inspect kit contents. An inventory of enclosed materials is provided for reference. 1. Using the marking pen provided, label all tubes, cryo-tubes, and cryo-cassettes with the date of sample and FB-11 Patient ID Number. 2. Place 6 pounds (3 kg) of dry ice pellets in the large shipping compartment within the kit and place the metal freezing platform on top of the dry ice to pre-cool. CAUTION: Handle the dry ice with caution using insulated gloves. Dry ice can cause severe frost-burns if allowed to come into direct contact with skin. 3. Leave the metal freezing platform to cool down for at least 5 minutes, covering the lower compartment using the kit lid. 4. Re-cover with the Styrofoam kit lid. Throughout the procedure, it is essential to keep the lid in place covering the dry ice when not directly working with the dry ice. Timing of submission Blood samples and fresh tissue samples should be shipped using the provided kit on the day they are procured (Monday through Thursday). (Do not ship on Friday or on the day before a holiday). Transmittal form (Form FT) FB-11 Forms: Baseline, Week 2, Week 14, and Surgery are included in the FB-11 Specimen Tracking System. Complete the appropriate form in the system and print. Use this form when shipping samples. Make a copy of the completed Form (see Section 2.4 for shipment instructions). Questions re: kits or requests for kits Contact DSSM ( , industry.trials@nsabp.org) to request kits once a patient is being screened. For questions related to kit contents or blood and fresh core specimens, contact pathology.questions@nsabp.org or Page 5 of 9

7 Sample collection and submission instructions (continued) 2.2 Blood sample collection and submission instructions Blood sample timing and requirements Blood sample collection instructions EDTA sample labeling PAXgene DNA blood sample (baseline only) PAXgene DNA sample labeling Questions re: blood samples EDTA blood samples will be collected at: Baseline (BEFORE study entry; on the same day as the baseline core biopsy.) Week 2 (BEFORE beginning Week 3 study therapy; on the same day as the Week 2 core biopsy). Week 14 (WITHIN 48 hours after the last dose of study therapy; on the same day as the Week 14 core biopsy.) A PAXgene DNA blood sample will be collected only at baseline, following the collection of the baseline EDTA blood sample. Optional EDTA blood samples: Patients who stop therapy before 14 weeks, and have received at least 1 cycle (4 weeks) of study therapy, will be asked permission for blood samples and core biopsies at that time. Notify DSSM and complete form Optional in the STS if collecting these samples. Please refer to your institutional policies and procedures for drawing blood specimens. The following are specific procedures related to the collection of specimens for transport to the NSABP Division of Pathology. EDTA blood sample (Lavender top): 1. Fill the 10ml EDTA tube completely. 2. Invert gently 8-10 times. 3. Centrifuge the sample at 1600 RCF (relative centrifugal force) with no brake. (If necessary, convert between RPM and RCF) for 8-10 minutes at 4 C. 4. Label the nunc cryo-tubes with the FB-11 patient ID number and date 5. Transfer PLASMA with a sterile pipette (provided in kit) to 1.8ml nunc cryo-tubes. Remove plasma slowly and carefully so as to not disrupt the layer of white blood cells. Note: Do not place the pipette tip near the buffy coat. 6. Place the nunc cryo-tubes into a 2 x 3 inch frozen specimen bag and seal. 7. Bury cryo-tubes in dry ice. Complete Form Baseline, or Week 2 or Week 14 in the FB-11 Specimen Tracking System and print a copy for submission. Make a copy of the Form for the patient's research record. PAXgene sample (PAXgene DNA tube): 1. Label the PAXgene DNA tube with the patient FB-11 ID number and date. 2. Fill the tube completely. 3. Invert gently 8-10 times. 4. The tube must be stored immobile and upright (use test tube rack if available). 5. Place the securely closed PAXgene tube into a re-sealable polythene bag and seal. 6. Place the bagged tube into the aluminium transport canister provided in the kit, immobile and upright. Store or transport sample at temperatures of C (59 86 F). Refrigerating samples prior to processing could adversely affect sample integrity. Complete Form Baseline in the FB-11 Specimen Tracking System and print a copy for submission. Make a copy of the form for the patient's research record. NSABP Division of Pathology at or pathology.questions@nsabp.org Page 6 of 9

8 Sample collection and submission instructions (continued) 2.3 Fresh tumor core biopsy collection and submission instructions Fresh tumor tissue sample (core biopsies) timing and requirements Fresh core samples (a total of 2-4 cores at each time point) from the breast tumor will be procured at: Baseline, before study entry Week 2, before beginning Week 3 study therapy; and Week 14, within 48 hours after the last dose of study therapy, At the time of definitive breast surgery (after completion of neoadjuvant therapy), following removal of gross residual disease 1cm. and collected in the following order: formalin fixed: first core (and third core, if obtained) fresh frozen: second core (and fourth core, if obtained): Note: Tumor samples and blood samples must be collected on the same day. Optional core biopsy and blood sample collection Formalin Fixed cores (first and third cores) Optional: Patients who stop therapy before 14 weeks, and have received at least 1 cycle (4 weeks) of study therapy, will be asked permission for core biopsies and blood samples for submission. Cores from consenting patients should be processed in the same order as described below. Notify DSSM and complete form Optional in the STS if collecting these samples. Using the provided 14 gauge sterile core biopsy gun obtain 2-4 duplicate cores of tumor from the patient or from the surgical specimen (at the time of definitive surgery if gross residual disease 1 cm.). Quality of the collected core specimens is essential. Cores containing tumor appear white and dense. Formalin fixed core biopsies : CAUTION: Formalin contains formaldehyde, which is a potential cancer hazard, highly toxic by inhalation. Irritant to eyes, skin, and respiratory tract. Avoid direct contact with skin and eyes. Wash hands thoroughly after handling. Follow institutional instructions for chemical spills. 1. Label the tube with the FB-11 patient ID number and date of collection. 2. DO NOT rinse this specimen in saline. Submerge the first core biopsy specimen in the 10% formalin tube. 3. If a third core is obtained, submerge the third core biopsy in the same 10% formalin tube as the first core. DO NOT rinse this specimen in saline. (Note: Use the 10% formalin tube for both biopsies. Two 10% formalin filled tubes are provided, one as back-up in case of spillage. 4. Place the 10% formalin tube in the small re-closable bag and then in the aluminum transport carrier provided in the kit. Page 7 of 9

9 Sample collection and submission instructions (continued) Fresh Frozen core processing (second and fourth core) Fresh frozen core biopsies Note: Steps 1-4 should be completed within 30 minutes of the biopsy procedure. The second and fourth core (if available) should be placed in the cryo-molds as soon after collection as possible (one core per mold). 1. Place two, square, clear plastic cryo-molds on pre-cooled steel freezing plate. Keep metal freezing plate on dry ice. 2. Place two cores (one core/mold) fully extended into cryo-molds and immediately cover each core with 4 ml OCT from provided pre-filled 10 ml OCT syringe. 3. Allow OCT to freeze completely. OCT is frozen when it is completely white and chalky in appearance. Once frozen, push on back of the cryo-mold to eject OCT pellet into a white cryocassettes (1 pellet per cryo-cassette). Close cryo-cassettes. 4. Place cryo-cassettes in the second 2 x 3 inch frozen specimen bag and seal. 5. Replace the steel freezing plate in its compartment in the upper tray, taking care not to touch it with bare hands. 2.4 Preparation of fresh tumor tissue and blood samples for shipping The shipping container is temperature validated to maintain samples at -70 C for up to 35 hours at 30 C ambient temperature (single use only). To ensure performance and to comply with the IATA Packing Instruction 650 for the shipment of diagnostic specimens, the following procedures must be followed: 1. Insert Form Baseline or Week 2 or Week 14 in the front flap of the 6x9 biohazard bag containing the samples. A copy of all Forms must be kept in the patient s study record. 2. Ensure that the two frozen specimen bags (1 containing the blood cryo-tubes and 1 containing the core cryocassette(s) are placed into the 6 x 9 inch biohazard bag with absorbent and seal. 3. Activate attached temperature marker on the 6 x 9 inch biohazard bag. Place the 6 x 9 inch biohazard bag with specimens in 6 pounds (3 kg) of dry ice in bottom chamber of kit and replace top tray. It is critical to cover the bag with at least 2 inches of dry ice. 4. Place aluminum transport canister containing the PAXgene DNA tube and the formalin fixed biopsy collection tube (first and third cores) in upper right circular chamber. DO NOT REMOVE THERMO CONTROL PANELS FROM KIT. This ensures that the samples enclosed in the thermos do not freeze. 5. Replace top lid and close outside carton. 6. Tape front of outside carton (center only) to secure. DO NOT SEAL FLAP SIDES. This allows necessary sublimation of the dry ice to maintain temperature. 7. Complete Dry Ice label and apply to the front flap, right side, adjacent to the UN3373 label: Include name and addresses: Shipper (institution/site) Consignee NSABP Foundation, Inc. Division of Pathology 1307 Federal Street, Suite 303 Pittsburgh, PA Number Pkgs "1 x 3 kg" Page 8 of 9

10 Sample collection and submission instructions (continued) Shipping address Questions regarding core biopsies Other FB-11 questions Ship all samples in one package using the provided air bill to: NSABP Foundation, Inc. Division of Pathology 1307 Federal Street Suite 303 Pittsburgh, PA NSABP Division of Pathology at or NSABP Department of Site and Study Management at PATIENT WITHDRAWAL OF PERMISSION FOR USE OF SPECIMENS If an enrolled patient chooses to withdraw permission for use of their specimens, submit Form Withdrawal in the FB- 11 specimen tracking system. Data obtained before submission of Form Withdrawal will be used; however, no additional data from the specimens will be obtained. For questions regarding use of the forms or patient withdrawal of specimens, contact DSSM at Note: Form Withdrawal is to be used only for patient-initiated withdrawal of permission for use of specimens. Page 9 of 9