Please select the eligibility criteria that correspond to the clinical trial below.
Title: MITO-11: A Randomized Multicentre Phase II Trial With Pazopanib and Weekly Paclitaxel vs Weekly Paclitaxel in Platinum Resistant or Refractory Ovarian Cancer
Brief Summary: The purpose of this study is to evaluate the safety and activity of adding pazopanib to weekly chemotherapy with paclitaxel for patients with ovarian cancer that is resistant or refractory to treatment with platinum based therapy.


Options:
A: DISEASE CHARACTERISTICS: Histologically confirmed stage III ovarian epithelial cancer or primary peritoneal carcinoma of one of the following cell types: Serous adenocarcinoma Mucinous adenocarcinoma Clear-cell adenocarcinoma Endometrioid Adenocarcinoma (not otherwise specified) Undifferentiated carcinoma Transitional cell Malignant Brenner's tumor Mixed epithelial carcinoma No borderline tumor (tumor of low malignant potential) Underwent prior standard initial cytoreductive surgery within the past 6 weeks Optimally resected disease with no residual site of disease more than 1 cm in greatest dimension Removal of all disease extending beyond the reproductive tract Total hysterectomy and bilateral salpingo-oopherectomy at cytoreductive surgery or in the past

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: GOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 3 times ULN SGOT no greater than 3 times ULN Renal: Creatinine no greater than 2.0 mg/dL Other: No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or breast No other major systemic medical illness that would preclude survival No poor general condition or medical, social, or psychosocial factors that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for current malignancy At least 5 years since prior gene therapy At least 1 year since prior interleukin-2 (IL-2) At least 1 year since prior sargramostim (GM-CSF) Concurrent filgrastim (G-CSF) allowed No concurrent gene therapy No concurrent GM-CSF No concurrent IL-2 No other concurrent angiogenesis inhibitors (e.g., thalidomide, cyclooxygenase-2 inhibitors (e.g., rofecoxib or celecoxib), interferon products, or angiotensin-converting enzyme inhibitors) Chemotherapy: At least 5 years since prior anticancer chemotherapy No prior chemotherapy for current malignancy No other concurrent chemotherapy Endocrine therapy: No prior endocrine therapy for current malignancy At least 1 year since prior tamoxifen No concurrent tamoxifen Radiotherapy: No prior radiotherapy for current malignancy Surgery: See Disease Characteristics Other: At least 1 year since prior experimental or investigational medications No other concurrent experimental or investigational medications
B: Inclusion Criteria:

* Cytologic / histologic diagnosis of stage IC-IV ovarian cancer
* Disease progressed during first line chemotherapy or disease relapsed within 6 months after the last platinum treatment
* Disease evaluable by RECIST or Ca 125 GCIG criteria
* No residual peripheral neurotoxicity from previous chemotherapy treatment
* PS 0-1
* Aged at least 18 and not greater than 75 years.
* Life expectancy of at least 3 months
* Able to swallow and retain oral medication
* Written informed consent prior to performance of study specific procedures or assessments
* Ability and willingness to comply with treatment and follow up assessments and procedures

Exclusion Criteria:

· • Previous or concomitant malignant neoplasia (not including basocellular or spinocellular skin carcinoma or in-situ carcinoma of the uterine cervix, provided they are being adequately treated)

* Previous treatment with weekly paclitaxel
* More than 2 previous chemotherapy treatments
* Serious heart disease, including heart failure, atrioventricular block of any degree, serious arrhythmia or history of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, coronary artery by-pass graft surgery, class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
* Hemoglobin \< 9 g/dL, neutrophils \< 1500/mm3, platelets \< 100000/mm3
* Impairment of renal function (patients should have 2 functioning kidneys): creatinine 1.5 times the upper normal limit - UNL; calculated creatinine clearance \< 50 mL/min; urine protein to creatinine ratio \> or = 1: then, a 24-hour urine protein must be assessed and subject must have a 24-hour urine protein value \<1gr to be eligible
* Impairment of liver function (SGOT or SGPT \> or = 2.5 UNL, alkaline phosphatase \> 2.5 ULN, total bilirubin \> 1.5 times the UNL)
* Prothrombin time (PT) or international normalized ratio (INR) or activated partial thromboplastin time (PTT) \> 1.2 times the UNL
* Pregnancy, breast feeding, or inadequate contraception
* Unable to discontinue prohibited medications (see protocol section 6.7)
* Clinically significant gastrointestinal abnormalities which might interfere with oral dosing, including but not limited to malabsorption syndrome, major resection of the stomach or small bowel that could affect drug absorption, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, 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, signs or symptoms of GI obstruction
* Any unstable or serious concurrent condition
* Prolongation of corrected QT interval (QTc) \>480 ms
* History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
* Macroscopic hematuria
* Major surgery or trauma within 30 days
* Hypertension uncontrolled with adequate therapy (systolic blood pressure (BP) of \> or = 140mmHg, or diastolic BP of \> or = 90mmHg)
* Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity
* Present or suspected haemorrhagic syndromes
* Patients' inability to access the centre due to area of residence
C: Inclusion Criteria:

* No evidence of disease on CT/MRI following treatment for recurrent ovarian, fallopian tube, or peritoneal cancer.
* High-grade papillary serous carcinoma of the ovary, fallopian tube or peritoneum. Histological confirmation of the original primary tumor is required.
* CA-125 within normal range.
* Age greater than or equal to 18 years.
* 1 prior line of therapy (cytotoxic therapy only) in the recurrent setting is allowed. Bevacizumab in the upfront setting allowed, however Bevacizumab or other VEGF pathway targeted therapy in the recurrent setting is not allowed. Hormonal therapy does not count as a prior line.
* Recovered from effects of recent surgery, radiotherapy, and chemotherapy.
* ECOG performance status ≤ 2

Organ and marrow function as defined below:

* Absolute neutrophil count ≥1,250/mcL
* Platelets ≥100,000/mcL
* Bilirubin ≤ 1.5 x ULN
* AST (SGOT) / ALT (SGPT) ≤ 2.5 x institutional upper limit of normal Alkaline phosphatase ≤ to 2.5 x ULN
* Creatinine ≤ 1.5 x institutional upper limit
* Less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than 1 week apart, or \< 1 gm protein on 24-hour urine collection or a urine protein:creatinine ratio of \< 1.
* INR \< 1.5; if on anticoagulation: INR is required to be between 2 and 3.

Patient must receive one of these three regimens for their platinum sensitive disease (number of cycles should not have exceeded 8 cycles of 1 regimen in the recurrent setting):

* Platinum (Carboplatin or Cisplatin) and Taxane (Paclitaxel or Docetaxel) Carboplatin and Gemcitabine
* Carboplatin and Liposomal Doxorubicin
* Females not of childbearing potential or has documentation of a negative pregnancy test prior to the start of the study treatment are eligible. Sexually active pre-menopausal female subjects must agree to use adequate, highly effective contraceptive measures, while on study and for 45 days after the last dose of last study drug. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) oral, implantable or injectable contraceptives plus one barrier method; or (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
* Able and willing to sign a written informed consent document.

Exclusion Criteria:

* Prior therapy with bevacizumab or other VEGF pathway targeted therapy in the recurrent setting. Bevacizumab in the upfront setting is allowed.
* Receiving any other study agents.
* Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible. Subjects with prior cancer treated with a curative intent with no evidence of recurrent disease 5 years following diagnosis and judged by the investigator to be at low risk of recurrence are eligible. Subjects with any other concomitant or prior malignancies are ineligible.
* Serious non-healing wounds or ulcers at the time of registration.
* History of abdominal fistula or gastrointestinal perforation.
* Active bleeding.
* Clinically significant cardiovascular disease.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Tivozanib.
* Symptomatic left ventricular dysfunction or baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) ≤ 50 % lower limit of institutional normal (LLN).
* Uncontrolled hypertension: systolic blood pressure of \>140 mmHg or diastolic blood pressure of \>90 mmHg documented on 2 consecutive measurements taken at least 24 hours apart.
* Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug.
* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation).
* Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication).
* Coronary or peripheral artery bypass graft within 6 months of screening.
* History of Class III or IV congestive heart failure, as defined by the New York Heart Association.
* Central nervous system metastases.

Note: Subjects with previously treated (radiotherapy or surgery) brain metastasis that have been stable without steroid treatment for at least 3 months following prior treatment may be enrolled.
D: Inclusion Criteria:

* Histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage (67) III or IV ovarian epithelial cancer or primary peritoneal cancer at presentation. Patients must have achieved a clinical complete response (disappearance of all clinical and radiological evidence of tumor) after only one regimen (4-6 cycles) of platinum and taxane-based standard chemotherapy received after tumor debulkment.
* Normal serum CA125 (cancer-associated tumor marker) level within 7 days of first dose of sorafenib.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* All scans used to document complete response must be done within 30 days prior to randomization.
* Patients must be able to swallow and retain oral medication.

Exclusion Criteria:

* Patients with any residual cancer tissue after the completion of chemotherapy detectable by standard Computed tomography (CT) or magnetic resonance imaging (MRI).
* Prior local radiotherapy, neoadjuvant chemotherapy or intraperitoneal chemotherapy.
* Histologic subtypes of ovarian cancer other than epithelial (i.e. sarcoma, lymphoma, germ cell).
* Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization.

Answer: B