Pazopanib vs. Pazopanib Plus Gemcitabine

  • STATUS
    Recruiting
  • End date
    Dec 28, 2023
  • participants needed
    107
  • sponsor
    North Eastern German Society of Gynaecological Oncology
Updated on 28 January 2021
Investigator
Alexander Mustea, Prof. Dr. med.
Primary Contact
Charit Campus Virchow-Klinikum Universit tsmedizin Berlin (8.8 mi away) Contact
+15 other location

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.

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.

Details
Condition Leiomyosarcoma or Carcinosarcoma
Treatment Pazopanib, Pazopanib plus Gemcitabine
Clinical Study IdentifierNCT02203760
SponsorNorth Eastern German Society of Gynaecological Oncology
Last Modified on28 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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 mol/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
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

Prior malignancy
Note: Subjects who have had another malignancy and have been disease-free for
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
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)
\. 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 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
\. 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
days prior to study enrolment
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