Pazopanib vs. Pazopanib Plus Gemcitabine

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT02203760

Studienbeginn:
Oktober 2019

Letztes Update:
30.11.2020

Wirkstoff:
Pazopanib plus Gemcitabine, Pazopanib

Indikation (Clinical Trials):
Leiomyosarcoma, Carcinosarcoma, Mixed Tumor, Mullerian

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
North Eastern German Society of Gynaecological Oncology

Collaborator:
Novartis Pharmaceuticals, medac GmbH,

Studienleiter

Alexander Mustea, Prof. Dr. med.
Study Chair
University Hospital, Bonn

Kontakt

Alexander Mustea, Prof. Dr. med.
Kontakt:
Phone: +49 (0) 0228 287 154 44
E-Mail: mustea@ukbonn.de» Kontaktdaten anzeigen

Eva Egger, Dr. med.
Kontakt:
E-Mail: eva-katherina.egger@ukbonn.de» Kontaktdaten anzeigen

Studienlocations
(3 von 9)

Helios Klinikum Bad Saarow, Hämatologie, Onkologie und Palliativmedizin, Sarkomzentrum
15526 Bad Saarow
(Brandenburg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Daniel Pink, Dr. med.
Phone: 033631 73527
E-Mail: daniel.pink@helios-gesundheit.de

Daniel Schöndube, Dr. med.
E-Mail: daniel.schoendube@helios-gesundheit.de» Ansprechpartner anzeigen

Helios Klinikum Berlin-Buch, Klinik für Onkologie und Paliativmedizin
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Peter Reichardt, PD Dr. med.
Phone: 030 94 01 54800
E-Mail: peter.reichardt@helios-gesundheit.de

Saeed Ghani, Dr. med
E-Mail: saeed.ghani@helios-gesundheit.de» Ansprechpartner anzeigen

Universitätsmedizin Berlin Charité Campus Virchow-Klinikum
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Jalid Sehouli, Professor Dr. med.
Phone: +4930/ 450 564 002
E-Mail: jalid.sehouli@charite.de

Radoslav Chekorov, Dr. med.
Phone: +4930/450-664399
E-Mail: radoslav.chekerov@charite.de» Ansprechpartner anzeigen

Universitätsklinikum Bonn
53127 Bonn
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Alexander Mustea, Prof. Dr.
Phone: +49228287154 44
E-Mail: mustea@ukbonn.de

Eva Egger, Dr.
E-Mail: eva-katherina.egger@ukbonn.de» Ansprechpartner anzeigen

Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden Klinik für Frauenheilkunde und Geburtshilfe
01807 Dresden
(Sachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Pauline Wimberger, Prof. Dr. med.
Phone: +49351/4 58 6728
E-Mail: pauline.wimberger@uniklinikum-dresden.de

Theresa Link, Dr. med.
Phone: +49351/458-18084
E-Mail: theresa.link@uniklinikum-dresden.de» Ansprechpartner anzeigen

Kliniken-Essen-Mitte Evang. Huyssens-Stiftung Klinik für Senologie / Brustzentrum
45136 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Phillip Harter, Dr. med.
E-Mail: p.harter@kliniken-essen-mitte.de

Florian Heitz, Dr. med.
E-Mail: f.heitz@kliniken-essen-mitte.de» Ansprechpartner anzeigen

Universitätsmedizin Greifswald Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
17475 Greifswald
(Mecklenburg-Vorpommern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Zaher Alwafai, Dr.
E-Mail: zaher.alwafai@med.uni-greifswald.de

Claudia Kolbe, Dr.
E-Mail: claudia.kolbe@med.uni-greifswald.de» Ansprechpartner anzeigen

Universitätsklinikum Jena
07747 Jena
(Thüringen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Ingo Runnebaum, Prof. Dr.
E-Mail: Ingo.Runnebaum@med.uni-jena.de

Matthias Rengsberger, Dr.
E-Mail: matthias.rengsberger@med.uni-jena.de» Ansprechpartner anzeigen

Universitätsfrauenklinik Tübingen
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Eva-Maria Grischke, Prof. Dr. med.
Phone: +497071/ 298 2212
E-Mail: eva-maria.grischke@med.uni-tuebingen.de

Andreas Hartkopf, Prof. Dr. med.» Ansprechpartner anzeigen

Alle anzeigen

Studien-Informationen

Detailed Description:

Study design:

This study is a prospective, randomized, open-label, multicenter phase II trial in order to

determine progression-free survival of patients with refractory or relapsed metastatic

uterine leiomyosarcomas or other metastatic uterine tumours.

Indication:

Relapsed or metastatic uterine leiomyosarcomas or carcinosarcomas

Randomization:

Patients with uterine leiomyosarcomas will be randomized in a 1:1-fashion to receive the

following therapy

- Arm A: Pazopanib 800 mg orally once daily plus Gemcitabine 1000 mg/m2 i.v. over 30 min d

1 and d 8 q3w or

- Arm B: Pazopanib 800 mg orally once daily Patients with uterine carcinosarcomas will be

treated according to Arm A.

Planned number of patients:

87 patients with uterine leiomyosarcomas 20 patients with uterine carcinosarcomas

Treatment schedules:

Patients with uterine leiomyosarcomas will be randomized in a 1:1-fashion to receive the

following therapy • Arm A (experimental arm / combination arm): Pazopanib 800 mg orally once

daily plus Gemcitabine 1000 mg/m2 i.v. over 30 min d 1 and d 8 q3w or

• Arm B (control arm / monotherapy arm): Pazopanib 800 mg orally once daily Patients with

uterine carcinosarcomas will be treated according to Arm A.

Planned treatment duration per subject:

Patients continue on study treatment until disease progression, death, unacceptable toxicity

or withdrawal of consent for any reason.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Subjects must provide informed consent prior to performance of study-specific

procedures or assessments, and must be willing to comply with treatment and follow-up.

Procedures conducted as part of the subject's routine clinical management (e.g., blood

count, imaging study) and obtained prior to signing of informed consent may be

utilized for screening or baseline purposes provided these procedures are conducted as

specified in the protocol

2. Histologically or cytological confirmed uterine leiomyosarcoma or uterine

carcinosarcoma including any subtypes

3. Patients with a contraindication for doxorubicin OR patients must have received prior

chemotherapies

4. For patients with prior anthracycline therapy normal cardiac function with LVEF at

least 50% must be assessed by quantitative echocardiogram or MUGA scan

5. Prior Gemcitabine containing chemotherapy is permitted provided that at least 8 weeks

have elapsed since the last dose of therapy

6. ECOG performance status 0-1

7. At least 18 years old

8. Measurable disease according to RECIST v 1.1 criteria (in case of tumour debulking -

staging CT-scan after surgery)

9. Able to swallow and retain oral medication

10. Adequate organ system function as defined in Table 1

Table 1: Definitions for Adequate Organ Function System Laboratory Values Hematologic

Absolute neutrophil count (ANC) > = 1.5 X 109/L Hemoglobin1 > = 9 g/dL (5.6 mmol/L)

Platelets > = 100 X 109/L Prothrombin time (PT) or international normalized ratio (INR)4 <=

1.2 X upper limit of normal (ULN) Partial thromboplastin time (PTT) <=1.2 X ULN Hepatic2

Total bilirubin <= 1.5 X ULN AST and ALT <= 2.5 X ULN Renal Serum creatinine <= 1.5 mg/dL

(133 µmol/L)

Or, if greater than 1.5 mg/dL:

Calculated creatinine clearance > = 50 mL/min

Urine Protein to Creatinine Ratio (UPC)3 < 1

1. Subjects may not have had a transfusion within 7 days prior to screening assessment.

2. Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN are not permitted

3. If UPC > = 1, then a 24-hour urine protein must be assessed. Subjects must have a

24-hour urine protein value <1g to be eligible.

4. Subjects receiving anticoagulant therapy are eligible if their INR is stable and

within the recommended range for the desired level of anticoagulation

11. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),

including any female who has had:

- A hysterectomy

- A bilateral oophorectomy (ovariectomy)

- A bilateral tubal ligation

- Is post-menopausal Subjects not using hormone replacement therapy (HRT) must have

experienced total cessation of menses for ≥ 1 year and be greater than 45 years in

age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40

mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).

Subjects using HRT must have experienced total cessation of menses for >= 1 year and be

greater than 45 years of age OR have had documented evidence of menopause based on FSH and

estradiol concentrations prior to initiation of HRT

OR

Negative serum pregnancy test of women of childbearing potential performed within 1 week

prior to the first dose of study treatment, preferably as close to the first dose as

possible, and agrees to use adequate contraception. Acceptable contraceptive methods, when

used consistently and in accordance with the product label and the instructions of the

physicians are as followed for 14 days before exposure to investigational product, through

the dosing period and for at least 21 days after the last dose of investigational product:

- Complete abstinence from sexual intercourse

- Oral contraceptive, either combined or progestogen alone

- Injectable progestogen

- Implants of levonorgestrel

- Estrogenic vaginal ring

- Percutaneous contraceptive patches

- Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate

of less than 1% per year

- Male partner sterilization (vasectomy with documentation of azoospermia) prior to the

female subject's entry into the study, and this male is the sole partner for that

subject

- Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps)

with a vaginal spermicidal agent (foam/gel/film/cream/suppository) Female subjects who

are lactating should discontinue nursing prior to the first dose of study drug and

should refrain from nursing throughout the treatment period and for 14 days following

the last dose of study drug.

Exclusion Criteria:

1. Prior malignancy

• Note: Subjects who have had another malignancy and have been disease-free for 5

years, or subjects with a history of completely resected non-melanomatous skin

carcinoma or successfully treated in situ carcinoma are eligible.

2. Patient has received prior treatment with any anti-angiogenic agent including

bevacizumab and tyrosine kinase inhibitors

3. Active malignancy or any malignancy in the last 5 years prior to first dose of study

drug other than LMS and CS

4. History or clinical evidence of central nervous system (CNS) or leptomeningeal

metastases, except for individuals who have previously-treated CNS metastases, are

asymptomatic, and have had no requirement for steroids or anti-seizure medication for

6 months prior to first dose of study drug. Screening with CNS imaging studies

(computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if

clinically indicated or if the subject has a history of CNS metastases

5. Clinically significant gastrointestinal abnormalities that may increase the risk for

gastrointestinal bleeding including, but not limited to:

- Active peptic 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 study treatment

- Grade 3/4 diarrhea

6. Corrected QT interval (QTc) > 450 Milliseconds using Barzett'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

- Class III or IV congestive heart failure, as defined by the New York Heart

Association (NYHA)

- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140

mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg].

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to

study entry. BP must be re-assessed on two occasions that are separated by a minimum

of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from

each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the

study (refer to study protocol for details on BP control and re-assessment prior to

study enrollment)

8. History of cerebrovascular accident including transient ischemic attack (TIA),

pulmonary embolism or untreated deep venous thrombosis (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

9. Major surgery or trauma within 28 days prior to study enrolment or any non- healing

wound, fracture or ulcer (procedures such as catheter placement not considered to be

major)

10. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs

chemically related to Pazopanib or Gemcitabine

11. Evidence of active bleeding or bleeding diathesis

12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

13. Hemoptysis in excess of 2.5 mL(or one half teaspoon) within 8 weeks prior to the first

dose of study drug

14. 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

15. Unable or unwilling to discontinue use of prohibited medications listed in the study

protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior

to the first dose of study drug and for the duration of the study

16. Treatment with any of the following anti-cancer therapies

- Radiation therapy, surgery or tumour embolization within 14 days prior to the

first dose of study drug

- Chemotherapy, immunotherapy, biologic therapy, investigational therapy or

hormonal therapy within 14 days or five half-lives of a drug (whichever is

longer) prior to the first dose of study drug

17. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is

progressing in severity, except alopecia

18. Pregnancy (for women of childbearing potential to be confirmed by negative serum

pregnancy test) or lactation period

Women of childbearing potential:

missing contraception (Pearl-Index <1, e.g. hormonal contraception including the

combined oral contraceptive pill, the transdermal patch, and the contraceptive vaginal

ring, intrauterine devices or sterilization) for 14 days before exposure to

investigational product, during study treatment and for at least 21 days after the

last dose of investigational product.

19. Medical or psychological conditions that would not permit the subject to complete the

study or sign informed consent

20. Legal incapacity or limited legal capacity

21. Participation in another clinical study with experimental therapy within 30 days prior

to study enrolment

Studien-Rationale

Primary outcome:

1. Progression free survival assessed as rate of patients without progression Second malignancy or clinical progression - patients with unknown or missing PFS will be treated as non-responder (Time Frame - 6 months)

Secondary outcome:

1. Objective response rate (RECIST v1.1 criteria) (Time Frame - One year):
Time to progression (TTP) of a patient being defined as the time in months from start of the first therapy cycle until PD is observed

2. Objective response rate (RECIST v1.1 criteria) (Time Frame - One year):
Overall survival (OS) calculated from the day of study enrolment until the day of death

3. Objective response rate (RECIST v1.1 criteria) (Time Frame - one year):
Progression-free survival (PFS) calculated from the day of study enrolment until the day of progression/death

4. Safety - side effects (Time Frame - One year):
Toxicity and tolerability

5. Quality of life (EORTC QLQ-C30) (Time Frame - One year):
Quality of life (EORTC QLQ-C30)

6. Translational research program (Time Frame - One year):
Translational research within a tumour bank

Studien-Arme

Experimental: Pazopanib plus Gemcitabine
Arm A: Pazopanib 800 mg orally once daily plus Gemcitabine 1000 mg/m2 i.v. over 30 min d 1 and d 8 q3w or
Active Comparator: Pazopanib
Pazopanib 800 mg orally once daily

Geprüfte Regime

Pazopanib plus Gemcitabine (Votrient and Gemzar):
Pazopanib 800 mg orally once daily plus Gemcitabine 1000 mg/m2 i.v. over 30 min d 1 and d 8 q3w or
Pazopanib (Votrient):
Pazopanib 800 mg orally once daily

Quelle: ClinicalTrials.gov

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