Please select the eligibility criteria that correspond to the clinical trial below.
Title: EWOC-1 Trial: Multicenter, Randomized Trial of Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer
Brief Summary: The current standard of first-line chemotherapy in advanced ovarian cancer is the combination of carboplatin AUC 5mg/mL/min and paclitaxel 175 mg.m-². This combination is feasible in selected elderly patients such as those included in prospective trials. These trials, however, include a minority of the elderly population. In wider selection of patients \>70 years old, the standard carboplatin-paclitaxel regimen has been shown to induce an excess of toxicity and premature treatment stopping. For elderly patients thought to be vulnerable and at high risk of toxicity with the standard 3-weekly carboplatin-paclitaxel regimen, other options are used in routine practice. One option is to delete paclitaxel and treat elderly patients with carboplatin as a single agent. An alternative is to use the carboplatin-paclitaxel regimen in a weekly schedule for both drugs such as reported by the MITO (Multicentre Italian Trial in Ovarian Cancer).

To date, there is no randomized trial which could give us some evidence of how to select patients who could benefit most of one or the other regimen described above. The 4th Ovarian Cancer Consensus Conference has indeed recognised the medical unmet need of adapted therapy for elderly patients with ovarian cancer and the necessity of additional research in this population.

Recently, GINECO has described a Geriatric Vulnerability Score (GVS) in a population of elderly patients with advanced ovarian cancer included in a specific multicenter phase II trial. The best proportional hazard model fitting for overall survival identified the following geriatric covariates score as being poor survival risk factors: ADL score \<6, IADL score \<25, HADS score \>14, albuminemia \<35g/L and , lymphopenia \<1G/L. GVS is the sum of these risk factors for each patient. Using a cut off of 3, the GVS identified a group of patients at high risk of severe toxicity, early cessation of treatment, unplanned hospitalization and adverse outcomes.

This international multicentre randomized phase II trial will compare the success rate of delivering 6 courses of chemotherapy with evidence of efficacy and without premature termination for progression, death or unacceptable toxicity of three different chemotherapy regimens in a selected population of elderly patients with a GVS ≥ 3:

* Arm A: Paclitaxel 175mg/m²/3 hours, I.V. and carboplatin AUC 5, I.V. every 3 weeks
* Arm B: Carboplatin monotherapy AUC 5 or 6 every 3 weeks
* Arm C: Weekly paclitaxel 60 mg/m²/1 hour and weekly carboplatin AUC 2 (d1, d8, d15 every 4 weeks)

The total number of patients to be enrolled is 240, ie 22 in each arm (total = 66) at the first step, then 58 more by arm (total=174) after interim analysis.


Options:
A: Inclusion Criteria:

* Patients with a histologic diagnosis of epithelial ovarian cancer, peritoneal primary carcinoma or fallopian tube cancer; International Federation of Gynecology and Obstetrics (FIGO) stage III with any gross (macroscopic or palpable) residual disease or FIGO stage IV, defined surgically at the completion of initial abdominal surgery and with appropriate tissue available for histologic evaluation; the minimum surgery required was an abdominal surgery providing tissue for histologic evaluation and establishing and documenting the primary site and stage, as well as a maximal effort at tumor debulking; if additional surgery was performed, it should have been in accordance with appropriate surgery for ovarian or peritoneal carcinoma described in the Gynecologic Oncology Group (GOG) Surgical Procedures Manual; however, the surgeon is not required to have performed all of the items contained in this section of the GOG Surgical Procedures Manual; those patients with stage III cancer in which the largest maximal diameter of any residual tumor implant at the completion of this initial surgery is no greater than 1 cm will be defined as "optimal;" all others will be defined as "suboptimal;" measurable disease on post-operative imaging studies is not required for eligibility
* Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.); however, the histologic features of the tumor must be compatible with a primary Müllerian epithelial adenocarcinoma; if doubt exists, it is recommended that the investigator should have the slides reviewed by an independent pathologist or, if necessary, the Pathology Co-Chair, prior to entry; patients may have co-existing fallopian tube carcinoma in-situ so long as the primary origin of invasive tumor is ovarian, peritoneal or fallopian tube
* Absolute neutrophil count (ANC) greater than or equal to 1,500/µl equivalent to Common Toxicity Criteria for Adverse Events version (v)3.0 (CTCAE) grade 1; this ANC cannot have been induced or supported by granulocyte colony stimulating factors
* Platelets greater than or equal to 100,000/µl; (CTCAE grade 0-1)
* Creatinine =\< 1.5 x institutional upper limit normal (ULN), CTCAE grade 1
* Bilirubin less than or equal to 1.5 x ULN (CTCAE grade 1)
* Serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE grade 1)
* Neuropathy (sensory and motor) less than or equal to CTCAE grade 1
* Prothrombin time (PT) such that international normalized ratio (INR) is =\< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus) and a partial thromboplastin time (PTT) \< 1.2 times the upper limit of normal
* Patients with a GOG Performance Status of 0, 1, or 2
* Patients must be entered between 1 and 12 weeks after initial surgery performed for the combined purpose of diagnosis, staging and cytoreduction
* Patients with measurable and non-measurable disease are eligible; patients may or may not have cancer-related symptoms
* Patients who have met the pre-entry requirements
* An approved informed consent and authorization permitting release of personal health information must be signed by the patient or guardian
* Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy as indicated at the lowest effective dose(s) for control of menopausal symptoms at any time, but not progestins for management of anorexia while on protocol directed therapy or prior to disease progression

Exclusion Criteria:

* Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian tube cancer treated with surgery only (such as patients with stage Ia or Ib low grade epithelial ovarian or fallopian tube cancers) are not eligible; patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated, new invasive epithelial ovarian, peritoneal primary or fallopian tube cancer are eligible, provided that they have not received prior chemotherapy for any ovarian tumor
* Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
* Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their ovarian, primary peritoneal or fallopian tube cancer are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
* Patients who have received any targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their epithelial ovarian or peritoneal primary cancer
* Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded, unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO grade 3 lesions
* With the exception of non-melanoma skin cancer and other specific malignancies as noted above, patients with other invasive malignancies who had (or have) any evidence of the other cancer present within the last five years or whose previous cancer treatment contraindicates this protocol therapy are excluded
* Patients with acute hepatitis or active infection that requires parenteral antibiotics
* Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations
* Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
* Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study
* Patients with clinically significant cardiovascular disease; this includes:
* Uncontrolled hypertension, defined as systolic \> 150 mm Hg or diastolic \> 90 mm Hg
* Myocardial infarction or unstable angina \< 6 months prior to registration
* New York Heart Association (NYHA) grade II or greater congestive heart failure
* Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate
* CTCAE grade 2 or greater peripheral vascular disease (at least brief (\< 24 hrs) episodes of ischemia managed non-surgically and without permanent deficit)
* History of CVA within six months
* Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
* Patients with clinically significant proteinuria; urine protein should be screened by urine protein-creatinine ratio (UPCR); the UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection; specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24 hour urine collection; obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine); send sample to lab with request for urine protein and creatinine levels \[separate requests\]; the lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL); the UPCR is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL); patients must have a UPCR \< 1.0 to allow participation in the study
* Patients with or with anticipation of invasive procedures as defined below:
* Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab/placebo therapy (cycle 2)
* Major surgical procedure anticipated during the course of the study; this includes, but is not limited to abdominal surgery (laparotomy or laparoscopy) prior to disease progression, such as colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second look surgery; please consult with the study chair prior to patient entry for any questions related to the classification of surgical procedures
* Core biopsy, within 7 days prior to the first date of bevacizumab/placebo therapy (cycle 2)
* Patients with GOG Performance Grade of 3 or 4
* Patients who are pregnant or nursing; bevacizumab should not be administered to nursing women; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of bevacizumab therapy
* Patients who have received prior therapy with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab
* Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition
* Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator should feel free to consult the study chair or study co-chairs for uncertainty in this regard
B: Inclusion Criteria:

* Woman \>70 year old
* Histologically or cytologically proven FIGO stage III to IV epithelial ovarian cancer or peritoneal primary or fallopian tube. A cytological proof is accepted if associated with a ratio of CA125/CEA \>25 and a radiological pelvic mass.
* GVS (Geriatric Vulnerability Score) \>3.
* Adequate bone marrow function including the following: Neutrophils ≥ 1.5 x 109/L , platelets ≥100 x 109/L and hemoglobin ≥9 g/dL.
* Adequate glomerular filtration rate \>40 ml/min (estimates based on MDRD or Chatelut formula are sufficient)
* No icterus.
* Life expectancy \> 3 months.
* Written informed consent obtained.
* Covered by a Health System where applicable

Exclusion Criteria:

* Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
* Prior history of chemotherapy.
* Prior history of radiotherapy which may affect patient tolerability to chemotherapy.
* Major perturbations of liver biology: Bilirubin \> 2 fold the upper normal limit (UNL), SGOT-SGPT \> 3 fold UNL.
* Patient unable to be regularly followed for any reason (geographic, familial, social, psychologic).
* Any mental or physical handicap at risk of interfering with the appropriate treatment.
* Known allergy to Cremophor ® EL -containing drugs.
* Any administrative or legal supervision where applicable
C: Inclusion Criteria:

* Histologically confirmed stage II-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer
* No prior chemotherapy
* Age: 20 and more
* Performance status: ECOG 0-3
* 1) Absolute neutrophil count at least 1,500/mm3 2) Platelet count at least 100,000/mm3 3) Bilirubin less than 1.5mg/dL 4) SGOT less than 100 IU/l 5) Serum creatinine less than 1.5mg/dL
* Written informed consent

Exclusion Criteria:

* Patients with ovarian borderline tumor
* Patients who have any evidence of the other cancer present within the last 5 years with the exception of carcinoma in situ or intramucosal cancer that is curable with local therapy
* Patients with active infection or uncontrolled diabetes
* Patients with unstable angina, or those who have had a myocardial infarction within the past 6 months, or patients with serious arrythmia that requires medication
* Patients who have a history of hypersensitivity to polyoxyethylated castor oil (Cremophor EL)
D: Inclusion Criteria:

* Cytologic or histologic diagnosis of ovarian carcinoma of the ovary, fallopian tube or primary peritoneal carcinoma, stage IC-IV
* Indication for chemotherapy
* Age \> 18 years
* Life expectancy of at least 3 months

Exclusion Criteria:

* Previous or concomitant malignant malignancy (excluding adequately treated baso-or squamocellular carcinoma of the skin and carcinoma in situ of the cervix, and synchronous endometrioid carcinoma Stage Ib or less for the uterus, with ovarian tumor Stage II or higher)
* Performance Status (ECOG) \> or = 3.
* Previous chemotherapy
* Heart disease (congestive heart failure, myocardial infarction within 6 months from study entry, atrioventricular block of any grade, severe arrhythmias)
* Neutrophils \< 2000 x mm3, platelets \< 100000 x mm3
* Inadequate renal function (creatinine \> or = 1.25 x normal values) or liver function (ALT or AST \> or = 1.25 x normal values)
* Present or suspected hemorrhagic syndromes
* Inability to comply with protocol and follow-up
* Inability to access study site for clinical visits
* Refusal of informed consent

Answer: B