fallopian tube cancer ovarian cancer
Conditions
Interventions
Treatment in the experimental arm: Paclitaxel 30 mg/m² weekly
Carboplatin 2.0
AUC weekly
Pazopanib 400 mg daily. Patients randomized to the experimental arm
will continue pazopanib (at the standard dose of 800 mg per day) after the
planned 18 courses of paclitaxel-carboplatin weekly unt
ovarian cancer
pazopanib
platinum-resistant
weekly paclitaxel carboplatin
Sponsors
European Organisation for Research in Treatment of Cancer (EORTC)
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Female subjects of age 18 years or older - Histologically confirmed diagnosis of ovarian, fallopian tube, or peritoneal carcinoma with recurrent disease - All patients with at least one earlier platinum treatment can be included but should be platinum resistant (progression between 28 days and 6 months after last platinum dose). There is no restriction on the number of prior lines. Non-platinum treatment after proven platinumresistance disease is allowed - Evaluable (measurable or non-measurable) disease by RECIST version 1.1 (CT or MRI from thorax, abdomen and pelvis: within 3 weeks before randomization) - Patient must be able to receive the infusions (paclitaxel, carboplatin and if applicable bevacizumab) and swallow the tablets (pazopanib) -WHO Performance status must be * 2 -LVEF assessed by ECHO or MUGA scan of the heart > 50%, if clinically indicated -Adequate organ function, see table page 19 -Patients with childbearing potential should have a negative serum pregnancy test, within 1 week before first day of treatment and use effective contraceptive methods for the whole duration of the study and for 6 months after discontinuing treatment -Patients who are lactating should discontinue nursing prior to the first dose -Patients must be able and willing to discontinue use of prohibited medications for at least 14 days (28 days for drugs with a longer half-life) prior to the first dose of study drug and for the duration of the study -Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
Exclusion criteria
Exclusion criteria: - prior treatment for recurrence with weekly paclitaxel (with or without weekly carboplatin). Prior bevacizumab is allowed -known metastatic disease to the brain or leptomeninges -other prior malignancies treated primarily or for recurrence within 2 years prior to inclusion in this study, except for completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma of the skin or cervix of the uterus - treatment with any of the following anti-cancer therapies: * Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of study drug * previous radiotherapy to the pelvis * chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days (28 days for drugs with a longer half-life) prior to the first dose of study drug -Patients with ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia and * Grade 2 peripheral neuropathy -Patients with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs similar or related to paclitaxel, carboplatin, bevacizumab and pazopanib. Mild infusion related reactions are allowed (see protocol) -Patients with unstable or serious condition e.g. uncontrolled infection requiring systemic therapy -prior major surgery or trauma within 28 days prior to the first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement and diagnostic endoscopic procedures not considered to be major) -history of any of the following cardiovascular conditions within 6 months before randomisation: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class II or greater congestive heart failure, as defined by the NYHA - inadequately controlled hypertension (systolic blood pressure (SBP) >150 mmHg, or diastolic blood pressure (DBP) >100 mmHg) despite intensive medical management or prior history of hypertensive crisis or hypertensive encephalopathy. Antihypertensive medication is allowed. Initiation or adjustment of blood pressure medication is permitted prior to the study entry . Initiation or adjustment of blood pressure medication is permitted prior to the study entry. - prolonged corrected QT interval (QTc) defined as >480 msecs using Bazett*s formula - history of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT), aorta-aneurysm requiring surgical repair or recent peripheral arterial thrombosis within 6 months prior to randomisation - evidence of active bleeding or bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). Current or recent (within 10 days) use of dipyridamole, ticlopidine, clopidrogel, cilostazol, prasugrel, ticagrelor, or use of full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose. HOWEVER prophylactic anticoagulation of venous access devices is allowed, provided PT, INR and aPTT is within normal limits within 1 week prior to randomization. Profylactic or therapeutic use of LMWH is allowed;- Obvious signs or risks of gastrointestinal fistula formation or perforation such as: - history of abdominal or tracheo-esophageal fistula or perforation within 6 mo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point: PFS defined by RECIST 1.1 at 1 year. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end points: - Response Rate - Overall Survival/ Progression Free Survival - Safety and tolerability of the combination, according to CTCAE 4.0 - Predictive biomarkers - Age related subanalysis for toxicity and efficacy (cut-off 65 years) | — |
Countries
Belgium, Netherlands, Spain
Outcome results
None listed