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

NCT01861951 | Completed Phase 2

• 2 other identifiers: STS0012011-004168-30
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 11

Brief Summary

Patients with 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 will be recruited for this study. The minimum age to enter the study is 60 years. Therapy with doxorubicin is the mainstay of palliative chemotherapy for these patients, which is associated with hematological toxicity and an increase of the infection rate. Pazopanib is known to rarely induce hematological toxicity or to trigger infection. We therefore assume that pazopanib exerts similar activity while 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 will 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 well 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.

Conditions

Soft Tissue Sarcoma

Keywords

soft tissue sarcoma; firstline treatment; eldery patients

Outcome Measures

Primary Outcomes (1)

• From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 40 months

  10 to 40 months

Secondary Outcomes (9)

• Change of rates of neutrophil granulocytopenia grade 4 (Day 1 - End of Trial (4 weeks after last IMP dose)), Change in rates of febrile neutropenia (Day 1 - End of Trial (4 weeks after last IMP dose))

  10 months up to 40 months

• Change from date randomization in progression-free rate at 12 weeks. Change from date randomization in progression-free rate at 26 weeks.

  10 months up to 40 months

• Change from date of randomization in overall survival to date of death (from any cause)

  10 months up to 40 months

• Change from date of randomization in objective response rate at 12 weeks. Change from date of randomization in objective response rate at 26 weeks.

  10 months up to 40 months

• Collection of life quality questionnaires (QLQ-C30) at baseline, after 3, 6, 9, 12, 15, 19, and 26 weeks from date of randomization and end of therapy (EOT). Thereafter, assessment will be performed every 12 weeks until progression.

  10 months up to 40 months

Study Arms (2)

Pazopanib

EXPERIMENTAL

Pazopanib 800 mg, p.o., daily Duration of treatment: Until disease progression, treatment failure, or death due to any cause, whichever occurs first

Drug: Pazopanib

Doxorubicin

ACTIVE COMPARATOR

Doxorubicin 75 mg/m² BSA, d1, q3wk, i.v. Duration of treatment: Six cycles (approximately 18 weeks) or until disease progression, treatment failure, or death due to any cause, whichever occurs first

Drug: Doxorubicin

Interventions

Pazopanib DRUG

Pazopanib

Doxorubicin DRUG

Doxorubicin

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Signed written informed consent and willingness to comply with treatment and follow-up. Procedures conducted within 3 weeks as 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
• 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 otherwise specified (NOS)
• Malignant peripheral nerve sheath tumors
• Other types of sarcoma (not listed as ineligible), if approved by the study coordinator.
• Excluding:
• \. ECOG performance status of 0-2
• \. Evidence of progressive disease prior to start of treatment with measurable disease according to RECIST 1.1

You may not qualify if:

• \. Prior malignancy Excluding: Subjects who have had another malignancy and have been disease-free for 2 years, or subjects with 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.
• \. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including but not limited to:
• Active peptide ulcer disease
• Known intraluminal metastatic lesion(s) with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease) or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning of study treatment
• \. Clinically significant gastrointestinal abnormalities that may affect absorption of IMP including but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowels
• \. Presence of uncontrolled infection
• \. QTc \> 480 msecs using Bazett's formula
• \. History of any one or more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina

Sponsors & Collaborators

• Hannover Medical School: lead

Study Sites (11)

University Hospitals Leuven, Leuven Cancer Institute, Dept. of General Medical Oncology

Leuven, Flemish Brabant, 3000, Belgium

Location

Heidelberg University Hospital, Department of Internal Medicine, Hematology, Oncology and Rheumatology

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University Medical Centre Mannheim, Surgical oncology

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Medical University Tuebingen, Center for Soft Tissue Sarcoma, GIST and Bone Tumors

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

LMU University hospital Munich Grosshadern, Medical Dept. III

Munich, Bavaria, 81377, Germany

Location

Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation

Hanover, Lower Saxony, 30625, Germany

Location

University Hospital RWTH Aachen, Medical Dept. IV

Aachen, North Rhine-Westphalia, 52074, Germany

Location

University Hospital Cologne

Cologne, North Rhine-Westphalia, 50937, Germany

Location

University Hospital Essen, West-German Tumor Center

Essen, North Rhine-Westphalia, 45122, Germany

Location

University Hospital Carl Gustav Carus, Internal Medicine Dept. I

Dresden, Saxony, 01307, Germany

Location

Charité Hospital, Medical Department, Division of Hematology, Oncology and Tumor Immunology

Berlin, 13353, Germany

Location

Related Publications (4)

• Hamacher R, Liu X, Schuler MK, Hentschel L, Schoffski P, Kopp HG, Bauer S, Kasper B, Lindner L, Chemnitz JM, Crysandt M, Stein A, Steffen B, Richter S, Egerer G, Ivanyi P, Kunitz A, Grunwald V. A post hoc analysis of the EPAZ trial: The role of geriatric variables in elderly soft tissue sarcoma patients on toxicity and outcome. Eur J Cancer. 2023 Mar;181:145-154. doi: 10.1016/j.ejca.2022.12.012. Epub 2022 Dec 27.

  PMID: 36657323 DERIVED

• Grunwald V, Karch A, Schuler M, Schoffski P, Kopp HG, Bauer S, Kasper B, Lindner LH, Chemnitz JM, Crysandt M, Stein A, Steffen B, Richter S, Egerer G, Ivanyi P, Zimmermann S, Liu X, Kunitz A. Randomized Comparison of Pazopanib and Doxorubicin as First-Line Treatment in Patients With Metastatic Soft Tissue Sarcoma Age 60 Years or Older: Results of a German Intergroup Study. J Clin Oncol. 2020 Oct 20;38(30):3555-3564. doi: 10.1200/JCO.20.00714. Epub 2020 Aug 24.

  PMID: 32840417 DERIVED

• Crombie JL, Armand P. Diffuse Large B-Cell Lymphoma's New Genomics: The Bridge and the Chasm. J Clin Oncol. 2020 Oct 20;38(30):3565-3574. doi: 10.1200/JCO.20.01501. Epub 2020 Aug 19. No abstract available.

  PMID: 32813609 DERIVED

• Karch A, Koch A, Grunwald V. A phase II trial comparing pazopanib with doxorubicin as first-line treatment in elderly patients with metastatic or advanced soft tissue sarcoma (EPAZ): study protocol for a randomized controlled trial. Trials. 2016 Jul 7;17(1):312. doi: 10.1186/s13063-016-1434-x.

  PMID: 27387325 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

pazopanib; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Viktor Gruenwald, MD, Prof.

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. , MD

Study Record Dates

• First Submitted: April 11, 2013
• First Posted: May 24, 2013
• Study Start: October 1, 2012
• Primary Completion: July 11, 2017
• Study Completion: July 11, 2017
• Last Updated: August 21, 2017

Record last verified: 2016-10

Locations

DE (10); BE (1)