Please select the eligibility criteria that correspond to the clinical trial below.
Title: ICON7 - A Randomised, Two-Arm, Multi-Centre Gynaecologic Cancer InterGroup Trial of Adding Bevacizumab to Standard Chemotherapy (Carboplatin and Paclitaxel) in Patients With Epithelial Ovarian Cancer
Brief Summary: RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and paclitaxel together with bevacizumab is more effective than carboplatin and paclitaxel alone in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

PURPOSE: This randomized phase III trial is studying carboplatin, paclitaxel, and bevacizumab to see how well they work compared with carboplatin and paclitaxel alone in treating patients with newly diagnosed ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer

  * Newly diagnosed disease
* Meets 1 of the following staging criteria:

  * High-risk stage I or IIA disease (grade 3 disease or clear cell carcinoma only)
  * Stage IIB-IV disease (all grades and all histological types)
* Must have undergone initial surgery (e.g., debulking cytoreductive surgery or a biopsy if the patient has stage IV disease) within the past 6 weeks

  * Patients with stage IV disease for which initial surgical debulking was not appropriate are eligible provided the following criteria are met:

    * Stage IV disease diagnosed by histology
    * No planned surgery prior to disease progression, including interval debulking surgery
* Patients with prior early-stage ovarian epithelial or fallopian tube carcinoma treated with surgery alone are eligible at the time of diagnosis of abdominopelvic recurrence provided no further interval cytoreductive therapy is planned prior to disease progression
* Synchronous primary endometrial carcinoma or a past history of primary endometrial carcinoma allowed provided the following criteria are met:

  * Disease ≤ stage IB
  * No more than superficial myometrial invasion
  * No lymphovascular invasion
  * Not poorly differentiated (i.e., no grade 3, papillary serous, or clear cell disease)
* Measurable or nonmeasurable disease
* No ovarian nonepithelial cancer, including malignant mixed Müllerian tumors
* No borderline tumors (e.g., tumors of low malignant potential)
* No history or clinical suspicion of brain metastases or spinal cord compression

  * CT scan or MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases
  * Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 12 weeks
* ANC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL (can be post-transfusion)
* INR ≤ 1.5
* APTT ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin ≤ 1.5 times ULN
* ALT and AST ≤ 2.5 times ULN
* Creatinine ≤ 2.0 mg/dL
* Proteinuria ≤ 1+ by urine dipstick OR ≤ 1 g by 24-hour urine collection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 weeks after completion of study therapy
* No significant traumatic injury within the past 4 weeks
* No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
* No other malignancies within the past 5 years except for adequately treated carcinoma in situ of the cervix, and/or basal cell skin cancer, and/or early endometrial carcinoma
* No pre-existing sensory or motor neuropathy ≥ grade 2
* No history or evidence of CNS disease (e.g., uncontrolled seizures) by neurological examination unless adequately treated with standard medical therapy
* No history or evidence of thrombotic or hemorrhagic disorders
* No uncontrolled hypertension (i.e., blood pressure \> 150/100 mm Hg despite antihypertensive therapy)
* No known hypersensitivity to bevacizumab and its excipients, chemotherapy, or Cremophor EL
* No nonhealing wound, ulcer, or bone fracture

  * Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require three weekly wound examinations
* No clinically significant cardiovascular disease, including any of the following:

  * Myocardial infarction or unstable angina within the past 6 months
  * New York Heart Association class II-IV congestive heart failure
  * Poorly controlled cardiac arrhythmia despite medication

    * Rate-controlled atrial fibrillation allowed
  * Peripheral vascular disease ≥ grade 3 (i.e., symptomatic and interfering with activities of daily living requiring repair or revision)
* No evidence of other disease or condition, metabolic dysfunction, physical examination findings, or laboratory findings that would contraindicate the use of an investigational drug or put the patient at high-risk for treatment-related complications

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 4 weeks since other prior surgery or open biopsy
* No prior systemic therapy for ovarian cancer (e.g., chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy, or hormonal therapy)
* Prior adjuvant chemotherapy allowed for other malignancies (e.g., breast or colorectal carcinoma) if malignancy was diagnosed over 5 years ago with no evidence of subsequent recurrence
* No prior mouse CA 125 antibody
* No prior radiotherapy to the abdomen or pelvis
* More than 10 days since prior and no concurrent chronic use of acetylsalicylic acid (\> 325 mg/day)

  * Low-dose (\< 325 mg/day) acetylsalicylic acid allowed
* More than 10 days since prior and no concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes

  * Use of therapy for line patency allowed provided INR \< 1.5
* More than 30 days since prior and no other concurrent investigational agent or participation in another clinical trial
* No other concurrent systemic antitumor agents
* No concurrent surgery
* No concurrent maintenance chemotherapy or intraperitoneal chemotherapy (including cytotoxic chemotherapy)
B: Inclusion Criteria:

* with recurrent epithelial carcinoma of the ovary, fallopian tube or primary peritoneum
* At least 1 previous line of chemotherapy
* Measurable disease
* Patients have a normal organ and bone marrow function measured within 28 days of randomization
* WHO 0-2

Exclusion Criteria:

* Primary platinum-refractory disease
* Known hypersensitivity to olaparib
* Resting ECG with QTc \> 470 msec
* Concomitant use of known potent CYP3A4 inhibitors
* Symptomatic uncontrolled brain metastases
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
C: Inclusion Criteria:

* Histologically or cytologically documented invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer
* Radiographically documented disease progression either on or following the last dose of the prior regimen for epithelial ovarian, primary peritoneal, or fallopian tube cancer
* Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound.
* Female 18 years of age or older at the time the written informed consent is obtained
* Adequate organ and hematological function

Exclusion Criteria:

* Subjects who have received more than 3 previous regimens of anti cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer
* Subjects treated with prior pegylated liposomal doxorubicin (PLD) or any anthracycline-based or mitoxantrone-based chemotherapy
* Subjects with primary platinum-refractory disease
* Subjects with platinum-free interval (PFI) \> 12 months from their last platinum based therapy
* History of central nervous system metastasis
* Major surgery within 28 days prior to randomization or still recovering from prior surgery
D: 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

Answer: A