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Ovarian cancer is most often recognized in advanced clinical state, the initial therapeutic strategies consist of a platinum containing chemotherapy subsequent to primary surgery. Although initially responsive to platinum-paclitaxel containing chemotherapy, a significant number of patients will show tumor progression during first line chemotherapy or relapse within six months after completion of first line chemotherapy, therefore being characterized as chemotherapy resistant. Any second line chemotherapy will result in approximately 10% of overall response, underlining the poor prognosis for these patients with an estimated median overall survival of 20 weeks.
In addition to conventional chemotherapeutics, so called small molecules are of high interest to establish new strategies in chemotherapy-refractory ovarian cancer (and in the long run first line chemotherapy). SU11248 is a polytargeting tyrosine kinase inhibitor.
SU11248 has demonstrated clinical efficacy in kidney cancer and GIST, further clinical trials have been initiated in other tumor entities. Growth pattern and biological targets present in ovarian cancer indicate that SU11248 might be a promising compound for the treatment of ovarian cancer. Especially, VEGFR, PDGFR and c-kit are specific targets for SU11248, which are expressed in ovarian cancer. The different targets of SU11248 provide a potential advantage of this compound compared to single-target molecules in chemotherapy-refractory ovarian cancer.
Full description
This study in patients with ovarian cancer refractory to platinum based chemotherapy is designed as a randomized, 2-schedule and dose-level, open-label, multicenter phase II study to select the better dose and schedule arm for further investigation.
72 patients will be randomized in a 1:1 ratio to receive oral SU11248 therapy either 37.5 mg/day continuously or 50mg/day for 4 weeks followed by 14 days off.
Patients will get outpatients treatment. At screening the patients' eligibility will be assessed, their baseline and demographic characteristics obtained, and the baseline values for the effect variables collected. Patients with measurable lesions as well as non-measurable disease will be included into this trial. Measurable lesion will be documented by CT or MRI scan and CA-125 values, non-measurable lesions will be monitored by analysis of CA°125 levels.
The patients' safety will be monitored during and up to 30 days after termination of SU11248 therapy.
In patients with measurable lesions at baseline, the (post)-treatment values for effect according to the RECIST criteria will be collected as shown in table 6. In case of CR or PR, a confirmatory CT or MRI scan is required after an interval of at least four weeks. Antitumor effects according to CA°125 levels will be determined in the same time intervals and, in addition, 28 days after last SU11248 application in patients with CA°125 response according to GCIG guidelines during therapy.
For post study follow-up, patients and/or their physicians will be contacted via phone for overall survival and TTP (including the method of diagnosis and additional treatment) every 2 months for their life time.
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Inclusion criteria
Adequate organ function as defined by the following criteria:
Exclusion criteria
Borderline tumor of the ovaries
Acute or chronic infection
Any required concurrent cancer chemotherapy or antineoplastic endocrine therapy or radiotherapy
Exposure to investigational trial medication, cancer chemo- or radiotherapy within the last 28 days prior to start of study treatment
Known or suspected hypersensitivity to investigational compound
Second malignancy interfering with prognosis of the patient
Cachectic patients with a body weight <45 kg
Patients requiring parenteral nutrition
Patients with ileus within the last 28 days
Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event
Current treatment with therapeutic doses of anticoagulant
Current treatment with CYP3A4 inhibitors or -inducers
Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
Ongoing cardiac dysrhythmias of NCI CTCAE grade >=2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec for females
Evidence of neurological signs/symptoms suggestive of brain metastases, spinal cord compression, or new evidence of brain or leptomeningeal disease
Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS)-related illness
Patients with any other severe concurrent disease, which is an undue risk for the patient by participating in the present study
Any further condition which according to the investigator results in an undue risk of the patient by participating in the present study
Major surgery, radiation therapy, or systemic therapy within 3 weeks of first study treatment. At least 7 days should elapse from the time of minor surgical procedure including placement of an access device or fine needle aspiration before randomization into this study can occur.
Wounds that have not completely healed, active ulcer(s), or bone fracture(s).
Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
Prior radiation therapy to >25% of the bone marrow.
Primary purpose
Allocation
Interventional model
Masking
73 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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