Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Phase II Study of Docetaxel Followed by Vandetanib (ZD6474) vs. Docetaxel Plus Vandetanib in Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Brief Summary: RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether docetaxel is more effective when given alone or together with vandetanib.

PURPOSE: This randomized phase II trial is studying docetaxel given together with or without vandetanib to see how well it works in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.


Options:
A: Inclusion Criteria:

* Diagnosis of ovarian epithelial, primary peritoneal, or fallopian tube cancer
* Recurrent disease
* Must have received a prior platinum-based regimen
* Platinum-sensitive (treatment-free interval \> 6 months)
* No more than 2 prior chemotherapy regimens
* Measurable disease
* At least 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan
* Not in a prior irradiation field
* No known brain metastases
* Performance status:

  * ECOG 0-2 OR
  * Karnofsky 80-100%
* Life expectancy:

  * More than 12 weeks
* Hematopoietic:

  * Absolute neutrophil count \>= 1,500/mm3
  * Platelet count \>= 100,000/mm3
  * Hemoglobin \>= 9 g/dL
  * No bleeding diathesis
* Hepatic:

  * Bilirubin \< 1.5 times upper limit of normal (ULN)
  * AST or ALT =\< 2 times ULN
* No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other agents used in the study
* Patients who have had a reaction to a taxane or a platinum and have not yet been rechallenged may undergo a desensitization regimen on study
* No hypersensitivity to paclitaxel or drugs using the vehicle Cremophor El:
* Prior hypersensitivity reaction to paclitaxel allowed provided rechallenged successfully
* Renal:

  * Creatinine \< 2 mg/dL
* Cardiovascular:

  * Abnormal cardiac conduction (e.g., bundle branch block or heart block) allowed if stable for the past 6 months
  * No symptomatic congestive heart failure
  * No uncontrolled hypertension
  * No cardiac arrhythmia
  * No unstable angina pectoris;
  * No myocardial infarction within the past 6 months
* Negative pregnancy test
* Fertile patients must use effective contraception
* Adequate intestinal function
* No concurrent requirements for IV hydration or nutritional support
* No active or ongoing infection
* No psychiatric illness or social situation that would preclude study compliance
* No other concurrent uncontrolled illness
* No other invasive malignancy with the past 5 years except nonmelanoma skin cancer
* More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
* More than 3 weeks since prior hormonal therapy
* More than 4 weeks since prior radiotherapy and recovered
* No prior sorafenib
* No prior anticancer therapy that contraindicates study therapy
* No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent therapeutic anticoagulation therapy
* Concurrent prophylactic low-dose warfarin allowed for maintenance of venous or arterial access devices
* No other concurrent anticancer therapies
* No other concurrent investigational agents
* Not pregnant or nursing
B: Inclusion Criteria:

1. Patients affected by pathologically confirmed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer.
2. Relapsed/progressive disease within 6 months from last platinum-based chemotherapy (platinum resistant/refractory disease).
3. Any line of treatment (after the first).
4. Any "last" chemotherapy line, including Paclitaxel, that should have been administered at least 6 months before the study beginning.
5. Patients must be women \> 18 years of age.
6. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:

   * Haemoglobin ≥ 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomization - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
   * White blood cells (WBC) \> 3x109/L
   * Platelet count ≥ 100 x 109/L
   * Total bilirubin ≤ 1.5 x institutional Upper Limit of Normal (ULN)
   * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional Upper Limit of Normal, unless liver metastases are present in which case it must be ≤ 5x ULN
   * Creatinine clearance estimated using the Cockcroft-Gault equation ≥51 mL/min,.
7. ECOG performance status 0-1.
8. Patients must have a life expectancy ≥ 16 weeks.
9. Evidence of non-childbearing status for women of childbearing potential (negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1 or postmenopausal women. Postmenopausal status is defined as:

   * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
   * LH and FSH levels in the post-menopausal range for women under 50
   * Radiation-induced oophorectomy with last menses \>1 year ago,
   * Chemotherapy-induced menopause with \>1 year interval since last menses
   * Surgical sterilization (bilateral oophorectomy or hysterectomy)
10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow up.
11. At least one lesion (measurable as defined by RECIST 1.1) that can be accurately assessed by CT scan or MRI with Chest X-ray at baseline and follow up visits.
12. BRCA1-2 mutation status known. In case of BRCA status unknown, the BRCA test must be performed before the randomization or, if not feasible, within the end-of the study treatment.
13. Provision of informed consent prior to any study specific procedures. In case of patients unable to give written informed consent, is necessary to have the subject or legal representative sign, but in any case a witness must be present and sign and date with the person providing informed consent.

Exclusion Criteria:

1. Any previous treatment with a PARP inhibitor, including Olaparib.
2. Prior treatment with Cediranib (previous bevacizumab or other antiangiogenic drugs are allowed)
3. Previous progression to weekly Paclitaxel
4. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years
5. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
6. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting Olaparib is 2 weeks.
7. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting Olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
8. Persistent toxicities (\>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
9. Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
10. Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein \< 1.5g in a 24 hr period or urine protein/creatinine ratio \< 1.5.
11. A history of poorly controlled hypertension or resting blood pressure \>150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy (measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2-minute intervals and averaged. If the first two diastolic readings differ by more than 5 mmHg, then an additional reading should be obtained and averaged).
12. Blood transfusions within 28 days prior to study start.
13. Features suggestive of Myelodysplastic syndrome or Acute myeloid leukemia (MDS/AML) on peripheral blood smear.
14. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
15. Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
16. Patients considered at poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent.
17. Patients unable to swallow medications and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
18. Breast feeding women.
19. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
20. Patients with known active hepatic disease (i.e., Hepatitis B or C).
21. Patients with a known hypersensitivity to Olaparib, Cediranib or any of the excipients of the products.
22. Patients with a known hypersensitivity to Paclitaxel.
23. Patients with uncontrolled seizures.
24. History of abdominal fistula or gastrointestinal perforation.
25. Prior gastrectomy.
C: Inclusion Criteria:

* Patients with a histologic diagnosis of mucinous adenocarcinoma of the ovary or fallopian tube with either optimal (=\< 1 cm residual disease) or suboptimal residual disease following initial surgery; patients may have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or no measurable disease
* All patients must have had appropriate surgery including appendectomy (unless patient has history of prior appendectomy) for ovarian or fallopian tube carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage
* Patients must have stage II-IV disease (new or recurrent-chemonaïve; no brain metastasis) or recurrent stage I disease (chemonaïve)
* Newly diagnosed patients must begin protocol therapy within 10 weeks of primary debulking; for stage I recurrent patients (chemonaïve), they should begin protocol therapy within 14 days of randomization
* Patients must have a negative colonoscopy within 1 year of enrolling in the study
* Absolute neutrophil count (ANC) \>= 1,500/mcl
* White blood cell (WBC) count \>= 3,000/mcl
* Platelets \>= 100,000/mcl
* Hemoglobin (Hgb) \>= 10 g/dl (can be post transfusion)
* Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) OR creatinine clearance \> 50 cc/min
* Bilirubin =\< 1.5 x ULN
* Serum glutamic oxaloacetic transaminase (SGOT) =\< to 2.5 x ULN
* Alkaline phosphatase =\< to 2.5 x ULN
* Neuropathy (sensory and motor) =\< Common Terminology Criteria for Adverse Events (CTCAE) grade 1
* Urine dipstick for proteinuria \< 2+; if urine dipstick is \>= 2+, 24 hour urine must demonstrate =\< 1 g protein in 24 hours OR patients must have a urine protein-to-creatinine ratio (UPCR) \< 1.0 mg/dL
* Prothrombin time (PT) =\< 1.5 x ULN
* Activated prothrombin time (APTT) =\< 1.5 x ULN
* Patients of childbearing potential must agree to practice an effective form of birth control during study treatment and for six months after completion of treatment
* Patients who have met the pre-entry requirements
* Patients must have signed an approved informed consent and authorization permitting release of personal health information
* Patients with Gynecologic Oncology Group (GOG) performance grade of 0, 1 or 2
* Patients with life expectancy \> 3 months

Exclusion Criteria:

* Patients with known colon cancer or history of colon cancer
* Patients with primary peritoneal carcinoma
* Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last 5 years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
* Patients who have received chemotherapy, radiotherapy or any investigational treatment for a gynecologic cancer (does include breast cancer) or colorectal cancer prior to enrollment
* Patients with a major surgical procedure anticipated during the course of the study; this includes but is not limited to: abdominal surgery (laparotomy or laparoscopy) 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
* Patients may have minor surgical procedures (i.e., mediport insertion) fine needle aspiration or core biopsies as long as it is performed \> 7 days prior to the first date of bevacizumab therapy and there is no evidence of wound disruption or impaired healing
* Patients with surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for fact that bevacizumab can be omitted from first cycle of chemotherapy)
* Patients with a history of abdominal fistula or perforation within the past 12 months
* Patients with a current, serious, non-healing wound, ulcer, or bone fracture; 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 known hypersensitivity to Chinese hamster cell products or other recombinant human or humanized antibodies
* Patients with mixed epithelial ovarian cancer histology
* Patients with tumors of low malignant potential
* History or evidence of upon physical examination of central nervous system (CNS) disease, including history of primary brain tumor or any history of brain metastases, or seizures not controlled with standard medical therapy
* Uncontrolled hypertension, defined as systolic \> 150 mm Hg or diastolic \> 100 mm Hg; patients with a history of hypertension are permitted
* Myocardial infarction or unstable angina within 12 months of the first date of bevacizumab therapy
* New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication; women who have received prior treatment with anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction \< 50% will be excluded from the study
* Grade 1, category 2 or greater, peripheral vascular disease; patient cannot have anything worse than mild, symptomatic claudication with exercise
* History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of bevacizumab therapy
* History of pulmonary embolism or deep vein thrombosis in the past 6 months
* Previous history of malabsorption or other conditions preventing oral treatment
* Patients who are pregnant or nursing
* Patients with acute hepatitis or active infection that requires parenteral antibiotics
* Patients with active bleeding or pathologic conditions that carry a high risk of bleeding such as a known bleeding disorder, coagulopathy or tumor involving the major vessels
* Patients taking warfarin
D: DISEASE CHARACTERISTICS:

* Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma

  * Recurrent, refractory, or progressive/persistent disease
* Measurable or non-measurable disease documented by CT scan of the abdomen and pelvis
* Must have received 1 prior platinum-based chemotherapy regimen for management of primary disease containing carboplatin, cisplatin, or other organoplatinum compound

  * Initial treatment may have included any of the following:

    * High-dose therapy
    * Consolidation therapy
    * Non-cytotoxic agent therapy
    * Extended therapy administered after surgical or non-surgical assessment
  * Additional cytotoxic regimen for recurrent, refractory, or progressive/persistent disease, including re-treatment with primary treatment regimen
* No more than 3 prior regimens for recurrent, refractory, persistent, or progressive disease.

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-2
* Absolute neutrophil count (ANC) ≥ 1,500/mcl
* Platelet count ≥ 100,000/mcl
* Serum creatinine normal OR calculated creatinine clearance ≥ 30 mL/min
* Urine protein:creatinine ratio \< 1
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* aspartate aminotransferase - alanine aminotransferase (AST or ALT) ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases are present)
* Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases are present)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 months after completion of vandetanib therapy
* No neuropathy ≥ grade 2 CTCAE v4.0
* No active infection requiring systemic or intravenous antibiotics
* No significant traumatic injury within the past 28 days
* No significant cardiovascular disease, including any of the following:

  * Uncontrolled hypertension (i.e., systolic blood pressure \[BP\] \> 140 mm Hg or diastolic BP \> 90 mm Hg) within the past 28 days
  * Myocardial infarction superior vena cava syndrome, or New York Heart Association (NYHA) class II-IV heart disease within the past 3 months
  * Presence of left bundle branch block
  * Congenital long QT syndrome or first degree relative with unexplained sudden death \< 40 years of age
  * QT interval with Bazett's correction that is unmeasurable or ≥ 480 msec by screening ECG
  * History of symptomatic arrhythmia (i.e., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) requiring treatment (≥ CTCAE grade 3) or asymptomatic sustained ventricular tachycardia

    * Atrial fibrillation controlled on medication allowed

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from all prior therapy (except alopecia) to NCI CTCAE v3.0 grade ≤ 1
* No prior vandetanib

  * Treatment with other anti-vascular endothelial growth factor (VEGF) targeted therapy allowed
* No prior docetaxel or any non-cytotoxic therapy (excluding hormonal therapy) for recurrent disease, regardless of whether it was part of primary treatment

  * Prior docetaxel as part of front-line cytotoxic regimen (including maintenance therapy) allowed as long as no disease progression on or within 6 months after receiving docetaxel
* At least 7 days since prior hormonal therapy for the malignant tumor

  * Concurrent hormone replacement therapy for menopausal symptoms allowed
* At least 28 days since other prior therapy for the malignant tumor, including immunologic agents
* More than 7 days since prior minor surgical procedures, fine needle aspirates, or core biopsies
* More than 14 days since prior and no concurrent potent inducers of cytochrome P450 3A4 (CYP3A4) function
* More than 14 days since prior and no concurrent medications having a risk of causing Torsades de Pointes or risk of QTc prolongation

  * Patients receiving a drug that has a risk of QTc prolongation must not have QTc ≥ 460 msec
* More than 28 days since prior investigational agents for any purpose
* More than 28 days since prior and no concurrent major surgical procedure or open biopsy
* More than 5 years since prior chemotherapy for abdominal or pelvic tumor, except treatment of ovarian, fallopian tube, or primary peritoneal cancer

  * Prior adjuvant chemotherapy for localized breast cancer allowed, provided it was completed more than 3 years prior to study, and the patient remains free of recurrent or metastatic disease
* More than 5 years since prior radiotherapy to any portion of the abdominal cavity or pelvis, except for the treatment of ovarian, fallopian tube, or primary peritoneal cancer

  * Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed, provided it was completed more than 3 years prior to study, and the patient remains free of recurrent or metastatic disease
  * No prior radiation to more than 25% of marrow-bearing areas

    * More than 28 days since prior radiotherapy
* No other concurrent investigational or commercial agents

Answer: D