A Trial Comparing Two Medications as First Treatment in Elderly Patients With Metastatic or Advanced Soft Tissue Sarcoma (EPAZ)

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1 A service of the U.S. National Institutes of Health Trial record 2 of 2 for: epaz Previous Study Return to List Next Study A Trial Comparing Two Medications as First Treatment in Elderly Patients With Metastatic or Advanced Soft Tissue Sarcoma (EPAZ) This study is currently recruiting participants. (see Contacts and Locations) Verified May 2014 by Hannover Medical School Sponsor: Hannover Medical School Information prov ided by (Responsible Party): Viktor Grünw ald, Hannover Medical School ClinicalTrials.gov Identifier: NCT First received: April 11, 2013 Last updated: May 20, 2014 Last verified: May 2014 History of Changes Full Text View Tabular View No Study Results Posted Disclaimer How to Read a Study Record Purpose Patients w ith a locally advanced or metastatic (i.e., there are already metastases of the diagnosed tumor in the body outside the primary lesion) soft tissue sarcoma w ill be recruited for this study. The minimum age to enter the study is 60 years. Therapy w ith doxorubicin is the mainstay of palliative chemotherapy for these patients, w hich is associated w ith hematological toxicity and an increase of the infection rate. Pazopanib is know n to rarely induce hematological toxicity or to trigger infection. We therefore assume that pazopanib exerts similar activity w hile decreasing neutropenia and neutropenic fever. Pazopanib is already approved in the U.S. and Europe for the treatment of advanced soft tissue sarcoma. Doxorubicin and pazopanib w ill be randomly allocated to either receive doxorubicin or pazopanib in a phase II clinical trial. The aim of this study is to measure the treatment effect (reduction in tumor size or tumor stabilization) for both drugs, as w ell as the survival rate, and the duration of tumor control by the different therapies. A further objective is to measure the quality of life by standardized questionnaires throughout the course of treatment. Condition Interv ention Phase Soft Tissue Sarcoma Drug: Pazopanib Drug: Doxorubicin Phase 2 Study Type: Study Design: Official Title: Interventional Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment A Randomized Phase II Trial Comparing Pazopanib With Doxorubicin as First Line Treatment in Elderly Patients With Metastatic or Advanced Soft Tissue Sarcoma Resource links prov ided by NLM: MedlinePlus related topics: Soft Tissue Sarcoma Drug Information available for: Doxorubicin Doxorubicin hydrochloride Pazopanib Genetic and Rare Diseases Information Center resources: Malignant Mesenchymal Tumor Soft Tissue Sarcoma U.S. FDA Resources

2 Further study details as prov ided by Hannov er Medical School: Primary Outcome Measures: From date of randomization until the date of first documented progression or date of death from any cause, w hichever came first, assessed up to 40 months [ Time Frame: 10 to 40 months ] [ Designated as safety issue: Yes ] Secondary Outcome Measures: Change of rates of neutrophil granulocytopenia grade 4 (Day 1 - End of Trial (4 w eeks after last IMP dose)), Change in rates of febrile neutropenia (Day 1 - End of Trial (4 w eeks after last IMP dose)) [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: Yes ] Change from date randomization in progression-free rate at 12 w eeks. Change from date randomization in progression-free rate at 26 w eeks. [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: Yes ] Change from date of randomization in overall survival to date of death (from any cause) [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: Yes ] Change from date of randomization in objective response rate at 12 w eeks. Change from date of randomization in objective response rate at 26 w eeks. [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: Yes ] Collection of life quality questionnaires (QLQ-C30) at baseline, after 3, 6, 9, 12, 15, 19, and 26 w eeks from date of randomization and end of therapy (EOT). Thereafter, assessment w ill be performed every 12 w eeks until progression. [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: No ] Geriatric assessments from the date of baseline, after 12 and 26 w eeks, and then every 12 w eeks until progression [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: No ] Change in expression of certain biomarkers in blood to predict either response or resistance to pazopanib from baseline, w eek 2, day 1 of every cycle, w eek 19 and 26, end of therapy, and as part of the extension study every 6 w eeks. [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: Yes ] Time from date of randomization until the date of first objective documentation of disease progression, treatment failure, or death due to any cause, w hichever occurs first. [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: Yes ] Time to onset of response after 6, 12, 19 and 26 w eeks from date of randomization [ Time Frame: 10 months up to 40 months ] [ Designated as safety issue: Yes ] Estimated Enrollment: 120 Study Start Date: October 2012 Estimated Study Completion Date: September 2016 Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure) Arms Experimental: Pazopanib Pazopanib 800 mg, p.o., daily Duration of treatment: Until disease progression, treatment failure, or death due to any cause, w hichever occurs first Active Comparator: Doxorubicin Doxorubicin 75 mg/m² BSA, d1, q3w k, i.v. Duration of treatment: Six cycles (approximately 18 w eeks) or until disease progression, treatment failure, or death due to any cause, w hichever occurs first Assigned Interv entions Drug: Pazopanib Drug: Doxorubicin Eligibility Ages Eligible for Study: Genders Eligible for Study: Accepts Healthy Volunteers: 60 Years and older Both No Criteria Inclusion Criteria: 1. Signed w ritten informed consent and w illingness to comply w ith treatment and follow -up. Procedures conducted w ithin 3 w eeks as

3 part of routine clinical management (e.g. blood count, imaging) and obtained prior to signing consent may be used for screening or baseline purposes if they are conducted as specified in the protocol 2. Male and female patients age 60 years at day of inclusion 3. Histologically confirmed diagnosis of metastatic or advanced soft tissue sarcoma of intermediate or high grade w ith disease progression w ithin 6 months prior to study inclusion: Excluding: Fibrosarcoma Pleomorphic high grade sarcoma ("malignant fibrous histiocytoma") Leiomyosarcoma Liposarcoma Malignant glomus tumor Rhabdomyosarcoma, alveolar or pleomorphic (excluding embryonal) Vascular sarcoma (epithelioid hemangioendothelioma, angiosarcoma) Synovial sarcoma Not otherw ise specified (NOS) Malignant peripheral nerve sheath tumors Other types of sarcoma (not listed as ineligible), if approved by the study coordinator. Uncertain differentiation (epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, malignant mesenchymoma, PEComa), chondrosarcoma, Ew ing sarcomas/pnet, chordoma, malignant solitary fibrous tumors, embryonal rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma (low -grade), neuroblastoma, malignant mesothelioma, and mixed mesodermal tumors of the uterus (Study inclusion is based on local histopathological diagnosis). 4. ECOG performance status of Evidence of progressive disease prior to start of treatment w ith measurable disease according to RECIST Preferably archived tumor tissue of the most recent histology or, if not available, tumor block or 8 representative unstained sections on slides must be provided for all subjects for biomarker analysis w ithin first month of treatment for central review 7. Adequate organ system function 8. Male patients w ith female partners of childbearing potential must meet one of the follow ing criteria: At least 6 w eeks after surgical sterilization by vasectomy w ith documentation of azoospermia Correct use of tw o reliable contraception methods for 14 days before exposure to IMP, through the dosing period, and for at least 21 days after the last dose of IMP. This includes every combination of a hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring) or an IUD/IUS w ith a barrier method (diaphragm, cervical cap, Lea contraceptive, femidom, or condom). Complete sexual abstinence for 14 days before exposure to IMP, through the dosing period, and for at least 21 days after the last dose of IMP. 9. Female patients of childbearing potential must have a negative serum pregnancy test w ithin 14 days of first dose of study treatment and agree to use effective contraception, as defined in Section "3.1 Inclusion criteria" during the study and for 14 days follow ing the last dose of investigational product. Exclusion Criteria: 1. Prior malignancy Excluding: Subjects w ho have had another malignancy and have been disease-free for 2 years, or subjects w ith a history of completely resected nonmelanomatous skin carcinoma, or successfully treated in situ carcinoma or incidental prostate cancer (TNM stage T1a or T1b) are eligible. 2. History or clinical evidence of CNS metastases Excluding: Subjects w ho have previously-treated CNS metastases (radiotherapy, surgery ± radiotherapy, radiosurgery, or gamma knife) and w ho meet both of the follow ing criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants 12 w eeks prior to study inclusion. Screening w ith CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases. 3. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including but not limited to: Active peptide ulcer disease Know n intraluminal metastatic lesion(s) w ith risk of bleeding Inflammatory bow el disease (e.g. ulcerative colitis, Crohn's disease) or other gastrointestinal conditions w ith increased risk of perforation History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess w ithin 28 days prior to beginning of study treatment 4. Clinically significant gastrointestinal abnormalities that may affect absorption of IMP including but not limited to: Malabsorption syndrome Major resection of the stomach or small bow els

4 5. Presence of uncontrolled infection 6. QTc > 480 msecs using Bazett's formula 7. History of any one or more of the follow ing cardiovascular conditions w ithin the past 6 months: Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease 8. Class III or IV congestive heart failure as defined by NYHA 9. Poorly controlled hypertension (SBP of 150 mmhg or DBP of 95 mmhg is acceptable provided that BP w ill be treated and monitored at least w eekly. The goal is to attain controlled hypertension w ithin 4 w eeks of start of IMP w hich is defined as grade 1 hypertension CTCAE Version 4.0) Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed tw ice w ith an interval of at least 1h before start of treatment and should be 140/90 mmhg for a subject to be eligible for the study. How ever, BP of 150/95 mmhg is acceptable provided the above measures are employed. 10. History of cerebrovascular accident including TIA, pulmonary embolism, or untreated DVT w ithin the past 6 months Note: Subjects w ith recent DVT w ho have been treated w ith therapeutic anti-coagulating agents for at least 6 w eeks are eligible. 11. Major surgery or trauma w ithin 28 days before first dose of IMP and/or presence of any non-healing w ound, fracture, or ulcer (procedures such as catheter placement are not considered to be major) 12. Evidence of active bleeding or bleeding diathesis 13. Know n endobronchial lesions and/or lesions infiltrating major pulmonary vessels 14. Hemoptysis in excess of 2.5 ml once w ithin 8 w eeks of first dose of IMP 15. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere w ith subject's safety, provision of informed consent, or compliance to study procedures 16. Unable or unw illing to discontinue use of prohibited medications (see Section 5.5.5) for at least 14 days or 5 half-lives of a drug (w hichever is longer) prior to the first dose of IMP and for the duration of the study 17. Treatment w ith any of the follow ing anti-cancer therapies: Radiation therapy, surgery, or tumor embolization w ithin 14 days prior to the first dose of IMP OR Chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy w ithin 14 days or 5 half-lives of a drug (w hichever is longer) prior to the first dose of IMP 18. Any ongoing toxicity from prior anti-cancer therapy that is CTCAE > grade 1 and/or that is progressing in severity except alopecia 19. Prior systemic therapy for metastatic or advanced disease. Neoadjuvant or adjuvant chemotherapy is allow ed, unless disease progression occurred w ithin 6 months follow ing end of treatment (see protocol chapter for specifics) 20. Current participation in any other clinical trial and/or participation in another clinical trial w ithin 30 days before the study begins 21. Know n hypersensitivity to any component of IMPs Contacts and Locations Choosing to participate in a study is an important personal decision. Talk w ith your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies. Please refer to this study by its ClinicalTrials.gov identifier: NCT Contacts Contact: Viktor Gruenw ald, MD, PD Gruenw ald.viktor@mh-hannover.de Locations Belgium University Hospitals Leuven, Leuven Cancer Institute, Dept. of General Medical Oncology Leuven, Flemish Brabant, Belgium, 3000 Contact: Patrick Schöffski, MD, MPH, Prof patrick.schoffski@uzleuven.be Principal Investigator: Patrick Schöffski, MD, MPH, Prof. Germany Heidelberg University Hospital, Department of Internal Medicine, Hematology, Oncology and Rheumatology

5 Heidelberg, Baden-Wuerttemberg, Germany, Contact: Gerlinde Egerer, MD, PD Principal Investigator: Gerlinde Egerer, MD, Prof. University Medical Centre Mannheim, Surgical oncology Mannheim, Baden-Wuerttemberg, Germany, Contact: Bernd Kasper, MD, PD Principal Investigator: Bernd Kasper, MD, PD Medical University Tuebingen, Center for Soft Tissue Sarcoma, GIST and Bone Tumors Tuebingen, Baden-Wuerttemberg, Germany, Contact: Hans-Georg Kopp, MD, PD Principal Investigator: Hans-Georg Kopp, MD, PD LMU University hospital Munich Grosshadern, Medical Dept. III Munich, Bavaria, Germany, Contact: Lars Lindner, MD, PD Principal Investigator: Lars Lindner, MD, PD Johann Wolfgang Goethe-University Frankfurt/Main, Medical Dept. II Frankfurt am Main, Hesse, Germany, Contact: Bjoern Steffen, MD Principal Investigator: Bjoern Steffen, MD Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hanover, Low er Saxony, Germany, Contact: Viktor Gruenw ald, MD, PD Gruenw Principal Investigator: Viktor Gruenw ald, MD, PD University Hospital RWTH Aachen, Medical Dept. IV Aachen, North Rhine-Westphalia, Germany, Contact: Martina Crysandt, MD Principal Investigator: Martina Crysandt, MD University Hospital Cologne Cologne, North Rhine-Westphalia, Germany, Contact: Jens Chemnitz, MD, PD Principal Investigator: Jens Chemnitz, MD, PD University Hospital Essen, West-German Tumor Center Essen, North Rhine-Westphalia, Germany, Contact: Sebastian Bauer, MD, PD Principal Investigator: Sebastian Bauer, MD, PD University Hospital Carl Gustav Carus, Internal Medicine Dept. I Dresden, Saxony, Germany, Contact: Markus Schuler, MD markus.schuler@uniklinikum-dresden.de Principal Investigator: Markus Schuler, MD University Hospital S-H, II. Medizinische Klinik und Poliklinik Kiel, Schlesw ig-holstein, Germany, Contact: Michael Kneba, MD, PhD, Prof m.kneba@med2.uni-kiel.de Principal Investigator: Michael Kneba, MD, PhD, Prof. Charité Hospital, Medical Department, Division of Hematology, Oncology and Tumor Immunology Berlin, Germany, Contact: Annegret Kunitz, MD annegret.kunitz@charite.de Principal Investigator: Annegret Kunitz, MD University Hospital Hamburg-Eppendorf, Medical Dept. II Hamburg, Germany, Contact: Martin Trepel, Professor, MD m.trepel@uke.de Principal Investigator: Martin Trepel, Prof., MD Sponsors and Collaborators Hannover Medical School Inv estigators Principal Investigator: Viktor Gruenw ald, MD, PD Hannover Medical School More Information

6 No publications provided Responsible Party: Viktor Grünw ald, PD, MD, Hannover Medical School ClinicalTrials.gov Identifier: NCT History of Changes Other Study ID Numbers: STS001, Study First Received: April 11, 2013 Last Updated: May 20, 2014 Health Authority: Germany: Federal Institute for Drugs and Medical Devices Keyw ords provided by Hannover Medical School: soft tissue sarcoma firstline treatment eldery patients Additional relevant MeSH terms: Sarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Connective and Soft Tissue Doxorubicin Liposomal doxorubicin Antibiotics, Antineoplastic Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses Topoisomerase II Inhibitors Topoisomerase Inhibitors ClinicalTrials.gov processed this record on October 29, 2014

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