SKCN E-Newsletter Volume 9 ISSUE 10 Regional Network Office

Transcription

1 SKCN E-Newsletter Volume 9 ISSUE 10 Regional Network Office Clinical Trials at your Fingertips The Jefferson Clinical Trials app allows you to quickly reference the TJU clinical trials database, including access to contact information for all trials. Download the app by searching Jefferson Clinical Trials On behalf of the Thomas Jefferson University s Sidney Kimmel Cancer Network, Cynthia Perez, BS, CCRP Poster Presented, The Development of the TJU NRG Oncology Reimbursement Process at the Society of Clinical Research Associates (SoCRA) on October 6-8, For more information, Anthony Roberts, BS or Anthony.Roberts@jefferson.edu IN THIS ISSUE Center Stage Clinical Trials App SKCC Featured Trials NCTN Updates Upcoming Events REFERRING A PATIENT? The SKCN has launched a new referreal address to streamline the process for for working together to provide our patients with personalized oncology treatment care. Please information to clinical-trial-referrals@jefferson.edu

2 Title: A Randomized Controlled Trial Evaluating the Use of G-CSF after Plerixafor-Mobilized Autologous Stem Cell Transplant (Auto HSCT) Sponsor: Thomas Jefferson University (TJU) PI: Neal Flomenberg, MD Primary Objective: To demonstrate non-inferiority in the number of days to discharge readiness after a G-CSF + Plerixafor mobilized autologous stem cell transplant in patients not receiving post-transplant G-CSF support versus those receiving post-transplant G-CSF growth factor support. Treatment: G-CSF + Plerixafor Age 18 years Undergoing autologous stem cell transplant for one of the following diagnoses: o Multiple myeloma o Non-Hodgkin lymphoma Karnofsky performance status of 70% Patients must meet the TJUH BMT SOP guidelines for Patient Criteria for Autologous HSCT. Adequate organ function: LVEF of >40% DLCO >45% of predicted corrected for hemoglobin Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal Serum creatinine 2.0 mg/dl and/or creatinine clearance of > 40 ml/min (excludes multiple myeloma patients receiving high dose Melphalan conditioning) Willingness to use contraception if childbearing potential Has the ability to give informed consent, or for cognitively or decisionally impaired individuals (vulnerable population), the availability of a family member or guardian to give consent and assist in the consent process Life expectancy of > 12 months (exclusive of the disease for which the Auto HSCT is being performed) Patients must have undergone stem cell mobilization with the combination of G-CSF and plerixafor as per TJUH BMT SOP guidelines Collection of an adequate number of CD34+ stem cells, i.e /kg from apheresis Uncontrolled HIV Uncontrolled bacterial infection Active CNS disease Pregnancy or lactation Evidence of another malignancy, exclusive of a skin cancer that requires only local treatment Gina Mateja Gina.Mateja@jefferson.edu Regional Network Office SKCN E-News 2

3 Title: A Phase III Study of AL3818 (Anlotinib) Hydrochloride Monotherapy in Subjects with Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma Sponsor: Advenchen Laboratories, LLC PI: Atrayee Basu-Mallick, MD Primary Objective: Indication A: To evaluate the efficacy of AL3818 for the treatment of ASPS, as measured by objective response rate (ORR) to exclude an ORR of 17% at the lower limit of the 95% confidence interval with an actual ORR of 31.1%. Indication B: To compare the efficacy of AL3818 versus dacarbazine for the treatment of LMS, as measured by progression-free survival (PFS). Indication C: To compare the efficacy of AL3818 versus dacarbazine for the treatment of SS, as measured by progression-free survival (PFS). Treatment: Indication A: Subjects with ASPS will receive AL3818 administered as one 12 mg capsule orally once daily in 21-day cycles for 14 days on treatment (Days 1-14) and 7 days off treatment (Days 15-21). Dose may be reduced to 10 mg or 8 mg, if needed. Indication B: Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or dacarbazine. Indication C: Subjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or dacarbazine. o AL3818 will be administrated as one 12 mg capsule orally once daily in 21-day cycles for 14 days on treatment (Days 1-14) and 7 days off treatment (Days 15-21). Dose may be reduced to 10 mg or 8 mg, if needed. o Dacarbazine will be administered at a dose of 1000 mg/m2 as a minute IV infusion on Day 1 of each 21-day treatment cycles. Indications: o Indication A ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma. o Indication B LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone). o Indication C SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma. Indications: o Indication A ASPS: Subjects with no prior therapy or subjects with prior treatment with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib). o Indication B LMS: Subjects previously treated with at least one prior line of approved therapy. o Indication C SS: Subjects previously treated with at least one prior line of approved therapy, including first-line anthracycline containing regimen. Show objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability (excluding ASPS subjects who have not received prior therapy) within 6 months of enrollment. ECOG performance status of 0 or 1. Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment. Prior treatment with or have known hypersensitivity to AL3818. o Indication A ASPS: Prior treatment with cediranib. o Indication B LMS: Prior treatment with or have known hypersensitivity to dacarbazine. o Indication C SS: Prior treatment with or have known hypersensitivity to dacarbazine. Previous or concurrent cancer that is distinct in primary site or histology from ASPS, LS, or SS within 5 years before enrollment except for curatively treated cervical cancer in situ, nonmelanoma skin cancer and superficial bladder tumors (Ta, Tis and T1). Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with any investigational product within 28 days of enrollment. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or prior treatment with extended-field radiotherapy for evaluating tumor lesions within 14 days prior to enrollment. Sarah Shaw Sarah.Shaw@jefferson.edu Regional Network Office SKCN E-News 3

4 Title: A Phase 1/2, Multicenter, Single Arm, Open Label, Dose Escalation Study of Birinapant in Combination with Pembrolizumab (KEYTRUDA ) in Patients with Relapsed or Refractory Solid Tumors Sponsor: Medivir AB PI: Russell Schilder, MD Primary Objective: To determine the safety and tolerability of the recommended phase 2 dose (RP2D) of birinapant when given in combination with pembrolizumab IV; to confirm the RP2D of birinapant/pembrolizumab combination in defined solid tumor patient populations. Treatment: During a 21 day treatment cycle, patients will receive 200 mg pembrolizumab intravenously (IV) on Day 1 and IV birinapant on Days 1 and 8. A week without treatment (i.e., Days 15 21) will follow the second week of treatment, immediately after which the next 21-day treatment cycle will start. All doses will be administered via a 30 minute (+10 min) IV infusion. Pembrolizumab will be administered first on Day 1. The birinapant infusion will begin 30 minutes (+ 10 minutes) following the completion of the pembrolizumab infusion on Day 1. Patients will be eligible to receive study medication for up to 35 treatment cycles or until documentation of disease progression or unacceptable toxicity. Inter patient dose escalation of birinapant will proceed at the birinapant dose indicated in the dose escalation table, below. A minimum of 3 and up to 6 evaluable patients will be enrolled per dose level. Dose Level Level -1 Level 1 Level 2 Level 3 Level 4 Dose-Escalation Schedule Pembrolizumab + Birinapant (per 21-day cycle) 2.8 mg/m2/week on Days 1 and mg/m2/week on Days 1 and 8 11 mg/m2/week on Days 1 and 8 17 mg/m2/week on Days 1 and 8 22 mg/m2/week on Days 1 and 8 The patient must have a histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients with tumors with mutations for which there are FDA-approved therapies must have progressed following these therapies in order to be eligible for this study. Patients with metastatic colorectal cancer should have progressed on prior fluoropyrimidine-based therapies, and have no curative therapies available to them, in order to be eligible for this study. Colorectal cancer patients should be assessed for microsatellite instability (MSI) status as per the local site routines. Patients must have measurable disease based on RECIST 1.1 as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. ECOG score of 0 or 1 at screening. Patients who have had a prior anti-cancer monoclonal antibody (mab) within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier prior to study Day 1. Patients who have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who have not recovered from adverse events due to a previously administered agent. Patients who are currently participating and receiving study therapy or who have participated in a study of an investigational agent and received study therapy or who have used an investigational device within 4 weeks of the first dose of treatment. Patients who have received prior therapy with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody or if the patient has previously participated in Merck MK-3475 clinical trials. Yuko Nishida Yuko.Nishida@jefferson.edu Regional Network Office SKCN E-News 4

5 Title: Phase 2, Randomized, Open-Label Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects with Newly Diagnosed Multiple Myeloma Eligible for High- Dose Chemotherapy and Autologous Stem Cell Transplantation Sponsor: Janssen PI: Joanne Filicko-O Hara, MD Primary Objective: To determine if the addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (D-RVd) will increase the proportion of subjects achieving stringent complete response (scr), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of postautologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone. Treatment: Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) Documented multiple myeloma as defined by the IMWG 2015 criteria including: Clonal bone marrow plasma cells 10%*. In addition, the patient must meet one of the criteria in 3a or 3b: o Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following): Hypercalcemia: serum calcium >0.25 mmol/l (>1 mg/dl) higher than the upper limit of normal (ULN) or >2.75 mmol/l (>11 mg/dl) Renal insufficiency: CrCl <40 ml/min (measured or estimated by validated equations, Attachment 2) or serum creatinine >177 μmol/l (>2 mg/dl) Anemia: hemoglobin value of >20 g/l below the lower limit of normal, or a hemoglobin value <100 g/l Bone lesions: 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or magnetic resonance imaging (MRI). o Any one or more of the following: Clonal bone marrow plasma cell percentage 60% Involved:uninvolved serum FLC ratio>100 >1 focal lesions on MRI studies; Each focal lesion must be 5 mm or more in size. Measurable disease as defined by any of the following: o Serum M-protein level 1.0 g/dl or urine M- protein level 200 mg/24 hours. Note: All attempts should be made to determine eligibility of the subject based on the central laboratory results of screening blood and urine M-protein measurements. In exceptional circumstances, the local laboratory results for blood and urine M- protein measurements may be used to determine eligibility, but only if the results are clearly above the thresholds for measurability; or o IgA, IgD, IgE, or IgM multiple myeloma: serum M-protein level 0.5 g/dl or urine M- Light chain multiple myeloma without measurable disease in the urine: serum Ig FLC 10 mg/dl and abnormal serum Ig kappa/lambda FLC ratio. Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease. ECOG performance status score of 0, 1, or 2 Diagnosed or treated for malignancy other than multiple myeloma, except: o Malignancy treated with curative intent and with no known active disease present for 3 years before randomization. o Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies with no evidence of disease. Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma. Jay Marshall Jason.Marshall@jefferson.edu Regional Network Office SKCN E-News 5

6 Title: A Randomized, Double-Blind, Placebo- Controlled Phase 3 Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Subjects with Extensive Stage Small Cell Lung Cancer (MERU) Sponsor: AbbVie PI: Rita Axelrod M.D. Primary Objective: Evaluate if rovalpituzumab tesirine improves progression-free and overall survival in subjects with extensive-stage SCLC who have ongoing clinical benefit (SD, PR, or CR) following the completion of 4 cycles of first-line, platinum-based chemotherapy (cisplatin or carboplatin plus irinotecan or etoposide) compared to placebo Treatment: Subjects will receive rovalpituzumab tesirine/placebo in combination with dexamethasone/ placebo on Day 1 of a 6 week cycle, omitting every third cycle until disease progression. Rovalpituzumab tesirine/placebo: 0.3 mg/kg, Day 1 of each 6-week cycle, omitting every third cycle. Dexamethasone/Placebo 8 mg orally (PO) twice daily on Day 1, Day 1 (the day of dosing), and Day 2 of each 6 week cycle, omitting every third cycle. Histologically or cytologically confirmed extensive-stage SCLC with ongoing clinical benefit (SD, PR, or CR per RECIST v.1.1) following completion of 4 cycles of first-line platinum-based therapy (cisplatin or carboplatin in combination with etoposide or irinotecan). Subjects with a history of CNS metastases prior to the initiation of first-line platinum-based therapy must have received definitive local treatment and have documentation of stable or improved CNS disease status based on brain imaging within 28 days prior to randomization, off or on a stable dose of corticosteroids. At least 3 but no more than 9 weeks between the administration of the last cycle of platinum-based chemotherapy and randomization. Availability of archived or representative tumor material for assessment of DLL3 expression. ECOG performance score of 0 or 1 Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to randomization. Subject must have adequate bone marrow, renal and hepatic function Any prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anti-cancer therapy than that described in 3 5 for the disease under study. Any disease-directed radiotherapy (except PCI or pre-planned radiotherapy for CNS metastases present prior to start of first-line therapy and nonprogressing) after last dose of first-line chemotherapy. Any significant medical condition including any suggested by screening laboratory findings that in the opinion of the Investigator or Sponsor may place the subject at undue risk from the study. Documented history of a cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III IV heart failure within 6 months prior to Randomization Documented history of capillary leak syndrome. Grade 2 or higher pleural or pericardial effusion within 4 weeks of randomization or earlier history of recurrent Grade 2 or higher effusions with ongoing requirement for pericardiocentesis or thoracentesis. Serious infection within 2 weeks prior to randomization, including any Grade 3 or higher viral, bacterial, or fungal infection. Systemic therapy with corticosteroids at > 10 mg/day prednisone or equivalent within 1 week prior to randomization. Subject has a history of active malignancies other than SCLC within the past 2 years prior to study entry, with the exception of in situ cancer which was curatively treated. Any prior exposure to a pyrrolobenzodiazepine (PBD)- or indolinobenzodiazepinebased drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity or other contraindications to rovalpituzumab tesirine or excipient contained in the drug formulation. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells. Linda Phan Linda Phan@jefferson.edu Regional Network Office SKCN E-News 6

7 NRG GU003: A Randomized Phase III Trial of Hypofractionated Post-Prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-Prostatectomy Radiation Therapy (COPORT) SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors NRG LU002: Maintenance Systemic Therapy Versus Consolidative Stereotactic Body Radiation Therapy (SBRT) Plus Maintenance Systemic Therapy for Limited Metastatic Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II/III Trial Alliance : Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Head of the Pancreas NCTN Central Nervous System Trials The NCTN Central Nervous System Trials Webinar will be held on Wednesday, October 25th at 3:00pm - 4:00pm EST. The study teams will discuss the trials scientific importance, research questions, trial design, key logistical and operational updates, and accrual strategies. Following each presentation, attendees will be able to ask questions and receive answers directly from the study teams. We encourage you to attend this webinar and learn more about these practice changing trials! The following protocols will be discussed: NRG-BN003: Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma A071401: Phase II Trial of SMO/AKT/NF2 Inhibitors in Progressive Meningiomas with SMO/ AKT/NF2 Mutations A071601: Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas Effective immediately NRG-HN001, Randomized Phase II and Phase III Studies of Individualized Treatment for Nasopharyngeal Carcinoma Based on Biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA), is temporarily closed to accrual. Due to inadvertent changes made in NRG-HN001 Amendment 5 (version date May 4, 2017; broadcast date June 26, 2017) the dosimetric criteria for the optic chiasm were increased to an unacceptable level. The criteria were correct in the previous protocol version (Amendment 4; version date April 14, 2016). NRG Oncology is in the process of submitting an amended protocol to CTEP/CIRB. We will reopen the protocol and distribute the amendment to sites immediately upon CTEP/CIRB approval. EAY131 (MATCH) Subprotocol U, is nearing the completion of its accrual goal, and only a limited amount of available treatment assignment slots remain. Patients currently enrolled on, or assigned to, this subprotocol should be treated and followed according to the Master Protocol and Subprotocol. ECOG E5202, A Randomized Phase III Study Comparing 5-FU, Leucovorin and Oxaliplatin vs 5-FU, Leucovorin, Oxaliplatin and Bevacizumab in Patients with Stage II Colon Cancer at High Risk for Recurrence to Determine Prospectively the Prognostic Value of Molecular Markers, continuing review CIRB approved. NRG-GU002, Phase II-III Trial of Adjuvant Radiotherapy and Androgen Deprivation Following Radical Prostatectomy With or Without Adjuvant Docetaxel, continuing review CIRB approved. ECOG 2805, ASSURE: Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma, continuing review CIRB approved. SWOG 1207, Phase III Randomized, Placebo-Controlled Clinical Trial Evaluating the Use of Adjuvant Endocrine Therapy +/- One year of Everolimus in Patients with High-Risk, Hormone Receptor Positive and HER2-Neu Negative Breast Cancer. e3 Breast Cancer Studyevaluating Everolimus with Endocrine, Revision 9 action letter posted on CTSU. NRG GY004, Phase III Study Comparing Single-Agent Olaparib or the Combination of Cediranib and Olaparib to Standard Platinum- Based Chemotherapy in Women with Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, Amendment 5 action letter posted on CTSU. Regional Network Office SKCN E-News 7

8 Upcoming SKCN Event: ECOG-ACRIN Semiannual Meeting October 26-28, 2017 Orlando, FL Save the Dates: Jefferson Oncology Group Annual Meeting: December 6, Philadelphia PA CRA Research Update: December 13, Philadelphia, PA NRG Oncology Semiannual Meeting: January 25-27, Phoenix, AZ ECOG-ACRIN Semiannual Meeting: May 3-5, Chicago IL NRG Oncology Semiannual Meeting: July 12-14, Philadelphia PA The Clinical Research E-News: Archive is now located on the Sidney Kimmel Cancer Center webpage under the SKCN Member Area: Sidney Kimmel Cancer Network Homepage: -This page contains links to the Remote Access Portal. Contact Information: Cynthia Perez, BS, CCRP NCTN Manager Editor, E-Newsletter Anthony Roberts, BS JOG Coordinator Co-Editor, E-Newsletter Joshua Schoppe, MPH, CCRP Senior Director, RNO Suzanne Jorfi, BS, CCRP Regulatory Manager Office: cynthia.perez@jefferson.edu Office: anthony.roberts@jefferson.edu Office: joshua.schoppe@jefferson.edu Office: suzanne.jorfi@jefferson.edu NRG Oncology, ECOG-ACRIN, CTSU or E-Newsletter inquiries JOG E-Newsletter inquiries RNO and SKCN inquiries Regulatory Update inquiries o CIRB Protocol Support Unit RNORegulatory@jefferson.edu Regulatory Related inquires For URGENT ISSUES, Please call the RNO cellphone at Regional Network Office SKCN E-News 8