The Clinical Research E-News Volume 7: ISSUE 11: November 20, 2015 Congratulations to Drs. Maria Werner-Wasik, Russell Schilder and Scott Goldstein for leading Thomas Jefferson University in recognition of excellence in study participant enrollment and data submission for NRG Oncology clinical trials. Under the direction of Dr. Maria Werner-Wasik, Thomas Jefferson University, a Main Voting Member Site, was listed at number five out of ten as a top accruing site in the Main membership category with 56 accrued subjects in 2014 and 42 to date in 2015. As Contact PI for Jefferson, Dr. Werner-Wasik oversees 31 NRG Oncology TJU affiliate institutions. A new link to IRBManager has been added to the Study Title section (see red arrow in image below) for each study approved by the CIRB and posted to the CTSU website. This link allows you to open a new IRBManager session without having to re-enter your IAM login information.
Title: A Phase III, Multicenter, Open-label, Randomized Study of nab-paclitaxel Plus Gemcitabine versus Gemcitabine Alone as Adjuvant Therapy in Subjects with Surgically Resected Pancreatic Adenocarcinoma (APACT) Sponsor: Celgene PI: Jordan Winter, MD Indication: nab-paclitaxel, in combination with gemcitabine, is indicated as adjuvant treatment in subjects with pancreatic adenocarcinoma following complete macroscopic surgical resection with no prior radiotherapy or neoadjuvant chemotherapy. Primary Objective: To compare disease-free survival (DFS) between subjects randomized to nab-paclitaxel in combination with gemcitabine and subjects randomized to gemcitabine alone Study Population: The study will enroll adult male and female subjects with confirmed resected pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1) and no evidence of metastases. Subjects will consent for study participation post-resection however subjects should be randomized to the study as early as adequately recovered from surgery, but no later than 12 weeks post-surgery. Subjects must have an ECOG performance status of 0 or 1 at screening, i.e. 14 days prior to randomization, and must have had no prior neoadjuvant treatment or radiation therapy for pancreatic adenocarcinoma. Study Treatments: Arm A will receive nab-paclitaxel 125 mg/m2 administered IV followed by gemcitabine 1000 mg/m2 given intravenously (IV) weekly on Days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles. Arm B will receive gemcitabine 1000 mg/m2 administered IV weekly on Days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles. Dose interruptions, and up to 2 dose reductions to 100 mg/m2 and 75 mg/m2 for nab-paclitaxel and 800 mg/m2 and 600 mg/m2 for gemcitabine, are allowed. Coordinator: Jamie Rothstein 215-955-9359 Jamie.Rothstein@jefferson.edu
Title: Multicenter, Open-Label, Randomized, Controlled Phase III Clinical Study of the Efficacy and Safety of Photodynamic Therapy Using Porfimer Sodium for Injection as Treatment for Unresectable Advanced Perihilar Cholangiocarcinoma Sponsor: Concordia Laboratories, Inc. PI: David Loren, MD Primary Objective: Overall survival from the date of randomization until the date of death or the last date the subject was known to be alive. Study Population: Male or female aged 18 years or older diagnosed with radiologically and biopsy or cytology confirmed inoperable perihilar cholangiocarcinoma Bismuth tumor Stage III/IV Condition: Hilar Cholangiocarcinoma Study Treatment: Drug: Photodynamic therapy-photofrin Photodynamic therapy (PDT) involves the i.v. injection of Photofrin (2 mg/kg) followed by the illumination of the tumor using a fiber optic device during an endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). Two days after the injection, a laser light (180 J/cm 2 will be applied to the tumor. A second light application will be given 96-120 hours after Photofrin injection if PDT could not initially be performed on all sides of the tumor. Post illumination, all patients will undergo stenting as part of standard medical care procedure. Up to 3 additional courses of PDT using a light dose of 120 J/cm 2 may be given at 3-month intervals. Arms: Photodynamic therapy-photofrin plus SMC Alternate Names: PDT-Photofrin Procedure: Stenting procedure As per standard medical procedures, stenting procedure consists in the placement of stents above the main tumors of the right and left hepatic bile ducts via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) when the ERCP approach has been unsuccessful. Arms: Photodynamic therapy-photofrin plus Standard Medical Care (SMC) Alternate Names: Stents placement Drug: Chemotherapy regimen Gemcitabine/Cisplatin The regimen will comprise gemcitabine (1 000 mg/m 2 ) followed by cisplatin (25 mg/m 2 ), each administered on days 1 and 8 every 3 weeks (21 day-cycle) for four cycles. An additional 12 weeks of the same chemotherapy regimen may be administered if there is no disease progression or intolerable toxicity. Arms: Photodynamic therapy-photofrin plus SMC Alternate Names: Gemcitabine/Cisplatin Study Coordinator: Cynthia Miller 215-955-8108 Cynthia.Miller@jefferson.edu
Title: A Phase III Study of Atezolizumab Treatment Versus Observation as Adjuvant Therapy in Patients With PD-L1 Positive, High Risk Muscle Invasive Bladder Cancer After Cystectomy Sponsor: Genentech/ Hoffmann-La Roche PI: Jean Hoffman- Censits, MD Purpose: Evaluate the efficacy and safety of adjuvant treatment with Atezolizumab compared with observation in participants with PD-L1-selected muscle-invasive bladder cancer (MIBC) who are at high risk for recurrence following cystectomy. Intervention: Cancer Biological: Atezolizumab (MPDL3280A) Inclusion Criteria: Histologically or cytologically confirmed muscle-invasive TCC of the bladder (excluding TCC of renal pelvis, ureters, or urethra) which is PD-L1 positive For patients who have not received prior neoadjuvant chemotherapy, refusal of or ineligibility for cisplatinbased adjuvant chemotherapy Representative tumor specimens as specified by the protocol Absence of residual disease and absence of metastasis, as confirmed by a negative baseline CT or MRI scan of the pelvis, abdomen, and chest no more than 6 weeks prior to randomization Full recovery from cystectomy within 12 weeks following surgery ECOG performance status of < 2 Life expectancy >/= 12 weeks Exclusion Criteria: Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment Adjuvant chemotherapy or radiation therapy for urothelial carcinoma (UC) following cystectomy Treatment with other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment Malignancies other than UC within 5 years prior to Cycle 1, Day 1 Pregnancy or breastfeeding Significant cardiovascular disease Severe infections within 4 weeks prior to randomization Major surgical procedure other than for diagnosis within 4 weeks prior to randomization History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation History of autoimmune disease Prior allogeneic stem cell or solid organ transplant History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Positive test for HIV and/or active hepatitis B or hepatitis C or tuberculosis Administration of a live, attenuated vaccine within 4 weeks prior to randomization Prior treatment with CD137 agonists or immune checkpoint blockade therapies Coordinator: Jennifer Louie Pager 877-656-7018 Jennifer.louie@jefferson.edu
Title: A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients with Brain Metastases (NRG-CC001) PI: Wenyin Shi, MD Primary Objective: Determine whether the addition of HA-WBRT increases time to neurocognitive failure at months 2, 4, 6 and 12 as measured by neurocognitive decline on a battery of tests: the Hopkins Verbal Learning Test-Revised (HVLT-R) for Total Recall, Delayed Recall, and Delayed Recognition, Controlled Oral Word Association (COWA), and the Trail Making Test (TMT) Parts A and B. Eligibility Criteria: Brain metastases outside a 5-mm margin around either hippocampus must be visible on contrastenhanced MRI performed 21 days prior to Step 1 registration. An allowed exception, regarding ability to image brain metastases, would be that patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a pre-surgery MRI or CT scan demonstrating brain metastases. However, the brain metastases could not have been within 5 mm of either hippocampus. Patients must have a gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) axial MRI scan with standard axial and coronal gadolinium contrast-enhanced T1-weighted sequence and axial T2/FLAIR sequence acquisitions. To yield acceptable image quality, the gadolinium contrast-enhanced threedimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm. The associated coronal and sagittal contrast-enhanced T1 sequences can be up to 2.5 mm in slice thickness. This MRI must be obtained 21 days prior to step 1 registration. The vendor specific MRI protocols are available for download from the Alzheimer s Disease Neuroimaging Initiative (ADNI), http://www.adni-info.org/scientists/mriprotocols.aspx. Ineligibility Criteria Prior external beam radiation therapy to the brain or whole brain radiation therapy. Planned cytotoxic chemotherapy during the WBRT only; patients may have had prior chemotherapy Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt. Severe, active co-morbidity defined as follows: o Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months o Transmural myocardial infarction within the last 6 months o Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration o Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of registration o Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease o Renal tubular acidosis or metabolic acidosis o HIV positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy
(HAART) and have a CD4 count 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. Pregnant or lactating women, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the medication involved in this study has unknown effects on the unborn fetus. Prior allergic reaction to memantine Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine) Intractable seizures while on adequate anticonvulsant therapy more than 1 seizure per month for the past 2 months Patients with definitive leptomeningeal metastases Patients with brain metastases from primary germ cell tumors, small cell carcinoma, unknown primary, or lymphoma. Contraindication to MR imaging such as implanted metal devices or foreign bodies Contraindication to gadolinium contrast administration during MR imaging, such as allergy or insufficient renal function Current use of (other NMDA antagonists) amantadine, ketamine, or dextromethorphan Study Coordinator: Radiation Oncology Protocol Group 215-955-8619 BR003: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel with or Without Carboplatin for Node-Positive or High- Risk Node-Negative Triple-Negative Invasive Breast Cancer A091401: Randomized Phase II Study of Nivolumab with or Without Ipilimumab in Patients with Metastatic or Unresectable Sarcoma EA6134: A Randomized Phase III Trial of Dabrafenib + Trametinib Followed by Ipilimumab + Nivolumab at Progression vs. Ipilimumab + Nivolumab Followed by Dabrafenib + Trametinib at Progression in Patients with Advanced BRAFV600 Mutant Melanoma NSABP B-52: A Randomized Phase III Trial Evaluating Pathologic Complete Response Rates in Patients with Hormone Receptor-Positive, HER2-Positive, Large Operable and Locally Advanced Breast Cancer Treated with Neoadjuvant Therapy of Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP) With or Without Estrogen Deprivation RTOG 1201: A Phase II Randomized Trial for Locally Advanced Unresectable Pancreatic Cancer :
Regulatory Update: 10/6/15 RTOG 0631-Amendment #9 revisions to protocol & consent 11/7/15 EAY131 MATCH-Amendment #1 revisions to protocol & consent 11/10/15 ECOG 1412-Amendment #6 revisions to protocol & consent CTSU Update: The CTSU hosted a Lung-MAP/ALCHEMIST webinar that highlighted these two high profile precision medicine studies. Both trials underwent important and exciting revisions this Fall and these changes were presented in a webinar that was broadcasted on Tuesday, October 27th, 2015. The webinar was recorded and is available on the CTSU site along with the all of the slides. If you would like to view the Lung-MAP/ALCHEMIST webinar, please visit the CTSU site. S0819, A Randomized Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): Eli Lilly and Company has posted their holiday schedule. Please be sure to have Cetuximab orders in no later than the following: Thanksgiving, orders must be in no later than 12:00 noon Eastern Time, Wednesday, November 11th to provide a drug delivery on or before Friday, November 20th. Christmas/New Year s Day, orders must be in no later than Wednesday, December 9th to provide a drug delivery on or before Friday, December 18th. Any orders received after this date will be filled when Eli Lilly resumes business on Monday, January 4, 2016. Eli Lilly will be closed from December 25, 2015 and reopen on Monday, January 4, 2015. There will not be any drug orders processed during this time. Please also note that there will not be any overnight or next day shipments. The soonest orders could be delivered would be Wednesday, January 6, 2016, so plan accordingly. EAY131 - Molecular Analysis for Therapy Choice (MATCH): A pause to all new accrual to the Screening (Step 0) portion of EAY131 started as of November 4, 2015. Screening (Step 0) accrual and related biospecimen processing have reached the accrual goals ECOG cont. necessary to conduct a study-specified planned analysis. EAY131 s protocol design has a built-in review after 500 patients are enrolled for mutation screening. The trial s enrollment has now reached 500 patients. To perform the review required by the protocol, new enrollments must pause until the analysis can be conducted. During this pause, the study team will use the time to thoroughly review data from the first 500 patients, and also examine all of the processes that support the study. The study team will continue to add new treatment arms to the trial as planned, to improve the frequency of matching mutations to drugs. This trial is expected to reopen in early 2016 with additional treatment trials available. Additional information will be provided as soon as it is available. IMPORTANT PROTOCOL EAY131, Molecular Analysis for Therapy Choice (MATCH): Upcoming CTSU Webinar for NCI- MATCH/EAY131 on Friday November 20th has been POSTPONED. As you may know, the MATCH protocol had a built in pause when 500 patients were accrued to the screening trial. Given the huge interest in the trial, this accrual goal was reached several months earlier than expected. During the scheduled pause, the NCI- MATCH study team will be conducting interim analyses and working toward adding new sub-studies to the trial. In addition, they will be addressing issues that have come to light during the accrual of the first 500 patients. The webinar will be re-scheduled for early 2016 and will highlight any changes and updates to the MATCH trial. Please stay tuned for an announcement of a new date. Protocol EAY131 (MATCH) biopsy payment information: Please note that "date of biopsy," information must be entered into the Oncology Patient Enrollment Network (OPEN) for all biopsies and biospecimen collections on EAY131 (MATCH) in order to receive payments for these activities. If you have registered a patient for screening since the study opened to accrual and will be seeking payment for biopsies and biospecimen collections, your prompt attention in entering this information is appreciated. Also, please remember that per the study specific notes within the funding sheet, if tissue is being collected under medically necessary procedures (e.g., surgery, endo, laproscopic, etc.), is considered standard of care (SOC) and being billed to insurance, or if the biopsy was not performed, do NOT complete the date in OPEN for the $3,000 biopsy tissue payments. Payments will not be made to offset partial reimbursements made through insurance carriers. The Thomas Jefferson University application to the NCI Central Institutional Review board for the EAY131 protocol was approved on October 22, 2015. If your site is interested in participating please contact Joshua Schoppe at your earliest convenience. E1412, Randomized Phase II Open Label Study of Lenalidomide R-CHOP (R2CHOP) vs RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) in Patients with Newly
ECOG cont. Diagnosed Diffuse Large B Cell Lymphoma, reopened to new accrual on October 13, 2015. The activation of Addendum #6 on October 13, 2015, re-opens protocol E1412 to new patient accrual. The Thomas Jefferson IRB has reviewed and approved this addendum effective on November 11, 2015 so new patient recruitment may begin. E1910, A Phase III Randomized Trial of Blinatumomab for Newly Diagnosed BCR-ABL-negative B lineage Acute Lymphoblastic Leukemia in Adults: Protocol Notice: Methotrexate Treatment Clarification: dosing information for the prophylactic administration of intrathecal Methotrexate in the protocol is inconsistent. Please refer to the following information regarding the proper dosing of the intrathecal Methotrexate for study treatment: Induction cycles: (Cycle 1) 12.5 mg IT day 14 only, (Cycle 2) 12.5 mg IT days 1, 8, 15, and 22 and Consolidation: 12.5 mg IT day 1. When planning patient treatment, please refer to the information above for correct dosing instructions. An amendment to clarify this information is in process and will be circulated as soon as possible. For questions regarding treatment information, please contact Dr. Mark Litzow at litzow.mark@mayo.edu or Dr. Ryan Mattison at rjmattison@medicine.wisc.edu. BN001, Randomized Phase II Trial of Hypofractionated Dose- Escalated Photon IMRT or Proton Beam Therapy Versus Conventional Photon Irradiation With Concomitant and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma: Amendment 1 (version date August 7, 2015; broadcast date September 14, 2005) contained an error in the sample informed consent form. The error is not expected to affect the willingness of current participants, and re-consent is not needed. Participating institutions may make this change now. RTOG 1010, A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma, is closed to accrual as of November 10, 2015 Upcoming Events: CRA Research Update Jefferson Campus December 16, 2015 NRG Semi-Annual Meeting: January 21-24, 2016 - Atlanta, GA Jefferson Lung Cancer Symposium: March 11, 2016 - Philadelphia, PA SKCN Research Coordinators Meeting: TBA CRA Research Update: March 18, 2016 - Virtual SKCN Social Workers Meeting: TBA SKCN Navigators Meeting: TBA ECOG-ACRIN Spring 2016 Meeting: May 12-14 - Boston, MA Palliative Care Symposium: June 3, 2016 - Philadelphia, PA
The Clinical Research E-News Archive is now located on the Sidney Kimmel Cancer Center webpage under the JKCCN Member Area: http://www.kimmelcancercenter.org/jkccn/e-newsletters.html Sidney Kimmel Cancer Network Homepage: http://isley.kcc.tju.edu/skcn/ -This page contains links to the Remote Access Portal as well as the clinical trial document repository. Contact Information: Cynthia Perez at 215-955- 9923 or cynthia.perez@jefferson.edu NRG Update inquiries or suggestions for future Clinical Research E-Newsletters Joshua Schoppe at 215-955-0448 or joshua.schoppe@jefferson.edu ECOG-ACRIN Update inquiries, CTSU, or CIRB Rashada Dawson at 215-955-2135 or rashada.dawson@jefferson.edu Pending Studies or Regulatory Update inquires For urgent clinical trial questions or assistance please page: 877-656-9004