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Leiomyosarcoma or CarcinosarcomaPhase 2PazoDobleNCT02203760

Pazopanib Vs. Pazopanib Plus Gemcitabine

A Phase 2 study testing Pazopanib plus Gemcitabine and Pazopanib in people with Leiomyosarcoma or Carcinosarcoma, run by North Eastern German Society of Gynaecological Oncology at 9 sites in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Leiomyosarcoma or Carcinosarcoma
What is being tested?
Pazopanib plus Gemcitabine and Pazopanib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
9 sitesGermany
Study dates
16 Oct 2019to 31 Dec 2024
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Histologically or cytological confirmed uterine leiomyosarcoma or uterine carcinosarcoma including any subtypes
  • Patients with a contraindication for doxorubicin OR patients must have received prior chemotherapies
  • For patients with prior anthracycline therapy normal cardiac function with LVEF at least 50% must be assessed by quantitative echocardiogram or MUGA scan
  • Prior Gemcitabine containing chemotherapy is permitted provided that at least 8 weeks have elapsed since the last dose of therapy
  • ECOG performance status 0-1
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  • At least 18 years old
  • Measurable disease according to RECIST v 1.1 criteria (in case of tumour debulking - staging CT-scan after surgery)
  • Able to swallow and retain oral medication
  • 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
  • Subjects may not have had a transfusion within 7 days prior to screening assessment.
  • Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN are not permitted
  • 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.
  • 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.

Who cannot join

  • 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.
  • Patient has received prior treatment with any anti-angiogenic agent including bevacizumab and tyrosine kinase inhibitors
  • Active malignancy or any malignancy in the last 5 years prior to first dose of study drug other than LMS and CS
  • 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
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
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  • 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
  • Corrected QT interval (QTc) > 450 Milliseconds using Barzett'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
  • 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)
  • 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
  • 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)
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Pazopanib or Gemcitabine
  • Evidence of active bleeding or bleeding diathesis
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
  • Hemoptysis in excess of 2.5 mL(or one half teaspoon) within 8 weeks prior to the first dose of study drug
  • 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
  • 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
  • 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
  • Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia
  • 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.
  • Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
  • Legal incapacity or limited legal capacity
  • Participation in another clinical study with experimental therapy within 30 days prior to study enrolment

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Germany9 sites

  • Helios Klinikum Bad Saarow, Hämatologie, Onkologie und Palliativmedizin, Sarkomzentrum

    Bad Saarow, 15526

  • Helios Klinikum Berlin-Buch, Klinik für Onkologie und Paliativmedizin

    Berlin, Germany, 13125

  • Universitätsmedizin Berlin Charité Campus Virchow-Klinikum

    Berlin, 13353

  • Universitätsklinikum Bonn

    Bonn, Bonn, 53127

  • Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden Klinik für Frauenheilkunde und Geburtshilfe

    Dresden, 01807

  • Kliniken-Essen-Mitte Evang. Huyssens-Stiftung Klinik für Senologie / Brustzentrum

    Essen, 45136

  • Universitätsmedizin Greifswald Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe

    Greifswald, Greifswald, 17475

  • Universitätsklinikum Jena

    Jena, 07747

  • Universitätsfrauenklinik Tübingen

    Tübingen, 72076

Other trials in Germany

About this study

Official title: Pazopanib Vs. Pazopanib Plus Gemcitabine in Patients with Relapsed or Metastatic Uterine Leiomyosarcomas or Uterine Carcinosarcomas: a Multi-center, Randomized Phase-II Clinical Trial of the NOGGO and AGO - PazoDoble -

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.

Read the 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.

Being tested
Pazopanib plus Gemcitabine, Pazopanib
Keywords
Relapsed/metastatic uterine leiomyosarcomas/carcinosarcomas
Medical subject headings
Leiomyosarcoma, Carcinosarcoma, Recurrence

What participants receive

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

  • Pazopanib plus GemcitabineDrug

    Also called 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

  • PazopanibDrug

    Also called Votrient

    Pazopanib 800 mg orally once daily

Study groups in NCT02203760
Study groupRoleWhat they receive
Pazopanib plus GemcitabineExperimentalArm A: Pazopanib 800 mg orally once daily plus Gemcitabine 1000 mg/m2 i.v. over 30 min d 1 and d 8 q3w or
Receives: Drug: Pazopanib plus Gemcitabine
PazopanibActive comparatorPazopanib 800 mg orally once daily
Receives: Drug: Pazopanib

What is being measured

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

  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

    Measured: 6 months

Secondary outcomes (6)

  1. Objective response rate (RECIST v1.1 criteria)

    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

    Measured: One year

  2. Objective response rate (RECIST v1.1 criteria)

    Overall survival (OS) calculated from the day of study enrolment until the day of death

    Measured: One year

  3. Objective response rate (RECIST v1.1 criteria)

    Progression-free survival (PFS) calculated from the day of study enrolment until the day of progression/death

    Measured: one year

  4. Safety - side effects

    Toxicity and tolerability

    Measured: One year

  5. Quality of life (EORTC QLQ-C30)

    Quality of life (EORTC QLQ-C30)

    Measured: One year

  6. Translational research program

    Translational research within a tumour bank

    Measured: One year

Timeline

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

  1. First posted30 Jul 2014 (estimated)
  2. Study start16 Oct 2019
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

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
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02203760
Sponsor's protocol ID
NOGGO U1
Other IDs
2012-003810-15
Acronym
PazoDoble
Status last verified
Nov 2024
First submitted
5 May 2014
Last updated
15 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pazopanib plus Gemcitabine and Pazopanib in people with Leiomyosarcoma or Carcinosarcoma, run by North Eastern German Society of Gynaecological Oncology at 9 sites in Germany.

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 35 inclusion and 40 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: under way, not looking for participants, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany. 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?

This study is still under way. Results are not available in the source record yet.

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?

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). 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 NCT02203760.

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 15 Nov 2024.

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