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 treated with Pazopanib plus Gemcitabine or Pazopanib alone. MedDRA version: 20.0 Level: LLT Classification code 10007508 Term: Carcinosarcoma uterus System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA vers
Conditions
Interventions
Trade Name: Gemedac
Product Name: Gemedac
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Gemcitabine
Other descriptive name: GEMCITABINE HYDROCHLORIDE
Concentration unit: m
Sponsors
NOGGO e.V.
Eligibility
Sex/Gender
All
Inclusion criteria
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. Patient must have received one or two 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 11. Non-childbearing potential or negative serum pregnancy test of women of childbearing potential Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: 1. Prior malignancy except 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. 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) > 480 msecs 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]. 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 therap
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •6 months progression free survival assessed as rate of patients without progression after 6 months •Second malignancy or clinical progression - patients with unknown or missing PFS at 6 months will be treated as non-responder ;Secondary Objective: •Objective response rate (RECIST v1.1 criteria) •Duration of response defined as the time in months from first assessment of CR or PR until the first date of PD or death •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 •Overall survival (OS) calculated from the day of study enrolment until the day of death. •Progression-free survival (PFS) calculated from the day of study enrolment until the day of progression/death •Toxicity and tolerability •Quality of life (EORTC QLQ-C30) •Translational research within a tumour bank ;Primary end point(s): Progression free survival (PFS) of Pazopanib plus Gemcitabine and of Pazopanib as a single agent in patients with leiomysarcoma according to RECIST v1.1 criteria assessed as rate of patients without progression at 6 months after study enrolment. ;Timepoint(s) of evaluation of this end point: 6 months after study enrolment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Response rate (RECIST v1.1 criteria), i.e. percentage of patients showing overall response (CR+PR), progression or stable disease • Duration of response defined the time in months from first assessment of CR or PR until the first date of PD or death • 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 • Overall survival (OS) calculated from the day of study enrolment until the day of death. The median survival is calculated using the Kaplan-Meier method and a 95% confidence interval will be reported. • Progression-free survival (PFS) calculated from the day of study enrolment until the day of progression/death • Toxicity and tolerability • Assessment of Quality of life over time as defined by EORTC-QLQ C 30 questionnaire • Translational research within the tumour bank ;Timepoint(s) of evaluation of this end point: • Response rate: 6 + 12 weeks after start of treatment 6, 9 and 12 months after start of treatment Thereafter every 6 months until PD (and any other time with an indication of a change in disease status). • Duration of response: time in months from first assessment of CR or PR until the first date of PD or death • Time to progression (TTP): from start of the first therapy cycle until PD is observed • Overall survival (OS): day of death. • Progression-free survival (PFS): day of study enrolment until the day of progression/death • Toxicity and tolerability during the whole study • Quality of life: before every treatment cycle + end of treatment, thereafter every 3 months • Translational research within the tumour bank: at the beginning of the study | — |
Countries
Germany
Outcome results
None listed