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Soft Tissue SarcomaPhase 2EPAZNCT01861951

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

A Phase 2 study testing Pazopanib and Doxorubicin in people with Soft Tissue Sarcoma, run by Hannover Medical School at 11 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
Pazopanib and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
11 sitesin 2 countries
Study dates
Oct 2012to 11 Jul 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. 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
  • 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 with disease progression within 6 months prior to study inclusion:
  • Fibrosarcoma
  • Pleomorphic high grade sarcoma ("malignant fibrous histiocytoma")
  • Leiomyosarcoma
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  • 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:
  • Uncertain differentiation (epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, malignant mesenchymoma, PEComa), chondrosarcoma, Ewing 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 0-2
  • 5. Evidence of progressive disease prior to start of treatment with measurable disease according to RECIST 1.1
  • 6. 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 within first month of treatment for central review
  • 7. Adequate organ system function
  • 8. Male patients with female partners of childbearing potential must meet one of the following criteria:
  • At least 6 weeks after surgical sterilization by vasectomy with documentation of azoospermia
  • Correct use of two 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 with 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 within 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 following the last dose of investigational product.

Who cannot join

  • 1. 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.
  • 2. History or clinical evidence of CNS metastases Excluding: Subjects who have previously-treated CNS metastases (radiotherapy, surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants 12 weeks prior to study inclusion. Screening with 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
  • 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
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  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 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 bowels
  • 5. Presence of uncontrolled infection
  • 6. QTc > 480 msecs using Bazett's formula
  • 7. History of any one or more of the following cardiovascular conditions within 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 will be treated and monitored at least weekly. The goal is to attain controlled hypertension within 4 weeks of start of IMP which 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 twice with 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. However, 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 within the past 6 months Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
  • 11. Major surgery or trauma within 28 days before first dose of IMP and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement are not considered to be major)
  • 12. Evidence of active bleeding or bleeding diathesis
  • 13. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
  • 14. Hemoptysis in excess of 2.5 mL once within 8 weeks of first dose of IMP
  • 15. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
  • 16. Unable or unwilling to discontinue use of prohibited medications (see Section 5.5.5) for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of IMP and for the duration of the study
  • 17. Treatment with any of the following anti-cancer therapies:
  • Radiation therapy, surgery, or tumor embolization within 14 days prior to the first dose of IMP OR
  • Chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy within 14 days or 5 half-lives of a drug (whichever 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 allowed, unless disease progression occurred within 6 months following end of treatment (see protocol chapter 5.4.2 for specifics)
  • 20. Current participation in any other clinical trial and/or participation in another clinical trial within 30 days before the study begins
  • 21. Known hypersensitivity to any component of IMPs

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

Germany10 sites

  • University Hospital RWTH Aachen, Medical Dept. IV

    Aachen, North Rhine-Westphalia, 52074

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

    Berlin, 13353

  • University Hospital Cologne

    Cologne, North Rhine-Westphalia, 50937

  • University Hospital Carl Gustav Carus, Internal Medicine Dept. I

    Dresden, Saxony, 01307

  • University Hospital Essen, West-German Tumor Center

    Essen, North Rhine-Westphalia, 45122

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

    Hanover, Lower Saxony, 30625

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

    Heidelberg, Baden-Wurttemberg, 69120

  • University Medical Centre Mannheim, Surgical oncology

    Mannheim, Baden-Wurttemberg, 68167

  • LMU University hospital Munich Grosshadern, Medical Dept. III

    Munich, Bavaria, 81377

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

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Belgium1 site

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

    Leuven, Flemish Brabant, 3000

Other trials in Belgium

About this study

Official title: A Randomized Phase II Trial Comparing Pazopanib With Doxorubicin as First Line Treatment in Elderly Patients With Metastatic or Advanced Soft Tissue Sarcoma

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.

Being tested
Pazopanib, Doxorubicin
Keywords
soft tissue sarcoma, firstline treatment, eldery patients
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01861951
Study groupRoleWhat they receive
PazopanibExperimentalPazopanib 800 mg, p.o., daily Duration of treatment: Until disease progression, treatment failure, or death due to any cause, whichever occurs first
Receives: Drug: Pazopanib
DoxorubicinActive comparatorDoxorubicin 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
Receives: Drug: Doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 10 to 40 months

Secondary outcomes (9)

  1. 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))

    Measured: 10 months up to 40 months

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

    Measured: 10 months up to 40 months

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

    Measured: 10 months up to 40 months

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

    Measured: 10 months up to 40 months

  5. 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.

    Measured: 10 months up to 40 months

  6. Geriatric assessments from the date of baseline, after 12 and 26 weeks, and then every 12 weeks until progression

    Measured: 10 months up to 40 months

  7. Change in expression of certain biomarkers in blood to predict either response or resistance to pazopanib from baseline, week 2, day 1 of every cycle, week 19 and 26, end of therapy, and as part of the extension study every 6 weeks.

    Measured: 10 months up to 40 months

  8. Time from date of randomization until the date of first objective documentation of disease progression, treatment failure, or death due to any cause, whichever occurs first.

    Measured: 10 months up to 40 months

  9. Time to onset of response after 6, 12, 19 and 26 weeks from date of randomization

    Measured: 10 months up to 40 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2013 (estimated)
  2. Study startOct 2012
  3. Primary completion11 Jul 2017
  4. Study completion11 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01861951
Sponsor's protocol ID
STS001
Other IDs
2011-004168-30
Acronym
EPAZ
Status last verified
Oct 2016
First submitted
11 Apr 2013
Last updated
21 Aug 2017
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 36657323

  • 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.

    PubMed 32840417

  • 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.

    PubMed 32813609

  • 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.

    PubMed 27387325

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pazopanib and Doxorubicin in people with Soft Tissue Sarcoma, run by Hannover Medical School at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 10 to 40 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01861951, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2017.

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