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

Phase 2
60 Years
Open (Enrolling)
Soft Tissue Sarcoma

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Trial Information

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

Inclusion Criteria:

- 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

- 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


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

- 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, 8 representative unstained sections on pretreated slides must be provided
for all subjects for biomarker analysis within first month of treatment for central

- 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

- 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.

Exclusion Criteria:

- 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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Outcome Time Frame:

10 to 40 months

Safety Issue:


Principal Investigator

Viktor Gruenwald, MD, PD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hannover Medical School


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

October 2012

Completion Date:

September 2016

Related Keywords:

  • Soft Tissue Sarcoma
  • soft tissue sarcoma
  • firstline treatment
  • eldery patients
  • Sarcoma