Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Placebo-Controlled Phase II Study of VTX-2337 in Combination With Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Brief Summary: The purpose of this study is to compare the overall survival of patients treated with VTX-2337 + pegylated liposomal doxorubicin (PLD) versus those treated with PLD alone in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.

VTX-2337, a small molecule agonist of Toll-like Receptor 8 (TLR8), activates multiple components of the innate immune system and is being developed as a novel therapeutic agent for use in oncology. Experimental data obtained in an animal model of ovarian cancer supports the combination of VTX-2337 with PLD. In this model, the combination of VTX-2337 and PLD resulted in a significant reduction in tumor growth compared to either agent alone and an increase in the number of T lymphocytes infiltrating the tumor. The combination of PLD and VTX-2337 has been tested in a small number of women with ovarian cancer in a Phase 1b study and appears to be generally well-tolerated.


Options:
A: Inclusion Criteria:

* Female subjects ≥ 18 years of age.
* Histologically confirmed progressive or recurrent endometrial cancer or ovarian cancer with previously identified ARID1A tumor mutations.

  a. Any ARID1A mutation is eligible and any CLIA Next generation sequencing test is allowable for eligibility.
* Archival tumor tissue specimen available. Histological tissue specimen (tissue block or 8-10 unstained slides) must be available (specimen can be the sample at diagnosis or taken at relapse). Otherwise, patient must agree to have tumor biopsy to obtain sufficient tissue for histological assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per MM discretion.
* A subset of patients (15 ovarian samples and 15 endometrial samples) should agree to have optional tumor biopsy for translational studies assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per medical monitor discretion. Tissue collection for the optional translational biopsies will continue until a total of 30 viable samples have been collected (15 endometrial and 15 ovarian). Patient agrees to have blood draw at pre-treatment and post-treatment (end of study) for translational studies assessment.
* Patients who have progressed after ≥1 prior platinum containing 5.2 regimen.
* Patient must agree to have blood draw at pre- and post-treatment for correlative studies.
* Measurable disease by RECIST criteria v1.1.
* ECOG performance status 0 or 1.
* Patients should have no major existing co-morbidities or medical conditions that will preclude therapy in the view of the principal investigator.
* Life expectancy \> 12 weeks.
* Adequate bone marrow, hepatic and renal function as defined by the following values within 14 days prior to starting treatment:

  1. Hemoglobin \>9 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
  2. Platelet count ≥ 100 x 109/L with no platelet transfusion in the past 28 days.
  3. Creatinine clearance ≥50 mL/min (estimated using Cockcroft-Gault equation).
  4. Total bilirubin ≤1.5 x institutional upper limit (ULN) (where bilirubin rise \> 1.5 x ULN due to Gilbert's syndrome a conjugated bilirubin ≤1.5 x ULN is required).
  5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 x ULN if no demonstrable liver metastases or ≤5 times ULN if patient has documented liver metastases.
* Women of child-bearing potential who are confirmed NOT to be pregnant. This should be evidenced by a negative urine or serum pregnancy test within 72 hours prior to start of trial treatment. Patients will be considered to be not of child-bearing potential if they are:

  1. Post-menopausal - defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, OR women under 50 years old who have been amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments and have serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma oestradiol levels in the post-menopausal range for the institution.
  2. Able to provide documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
  3. Radiation or chemotherapy-induced oophorectomy or menopause with \> 1 year since last menses.
* Patient is willing and able to comply with the protocol for the duration of the study. including undergoing treatment and scheduled visits and examinations.
* Able to swallow, absorb, retain oral medication.
* Able to provide written, informed consent.
* Patients must have recovered from any effects of any major surgery and not have an open wound, active ulcer, or fistula.

Exclusion Criteria:

* Patients with localized advanced disease without other measurable lesion and could be treated with curative intent.
* Other malignancy within the last 5 years that would be expected to impact on overall survival. Prior malignancy with no expected impact on overall survival are allowed.
* Patients with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML.
* Patients receiving radiotherapy within 2 weeks prior to study treatment.
* Major surgery within 4 weeks of starting study treatment.
* Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
* Any previous treatment with PARP inhibitor, including niraparib.
* Clinically significant (e.g. active) cardiovascular disease, uncontrolled high blood pressure. Uncontrolled high blood pressure defined as values ≥160/100 or symptomatic, refer to CTCAE.
* Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to study treatment.
* Patients with increased risk of bleeding or history or evidence of hemorrhagic disorders within 6 months prior to study treatment.
* Resting ECG with QTc \> 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome
* Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) \> grade 2) caused by previous cancer therapy, excluding alopecia.
* 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 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
* Patients considered a 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, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
* Pregnant or lactating woman.
* Participation in another clinical study with an investigational product during the chemotherapy course within 30 days prior to study treatment.
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
* Patients with a known hypersensitivity to investigational drugs or excipients.
* Clinical/radiological evidence of bowel obstruction (e.g. hospitalization) or symptoms of sub-acute bowel obstruction within 6 weeks prior to trial entry.
B: Inclusion Criteria:

* Subjects meeting all of the following criteria will be considered for enrollment in the study:

  * Availability of subject for the entire study period and willingness to adhere to protocol requirements.
  * Patients with documented diagnosis of Ovarian Cancer and eligible for receiving a dose 50mg/m2 of Doxorubicin liposome(preferably on no other concomitant medication, however, if considered necessary, to be documented and given).
  * Patients at least 18-years of age or older. iv. Subjects who have no evidence of underlying disease (except ovarian cancer) during screening medical history and whose physical examination is performed within 21 days prior to commencement of the study.
  * Patients with Performance ≤ 2 on the ECOG performance scale. vi. Subjects whose screening laboratory values are within normal limits or considered by the clinical Investigator/Co-Investigator to be of no clinical significance.
  * Informed consent form given in written form.

Exclusion Criteria:

* History or presence of significant:

  * Allergy or Significant history of hypersensitivity or idiosyncratic reactions to Doxorubicin Hydrochloride and/or any related compounds etc.
  * Cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunologic, dermatologic, musculoskeletal, neurological or psychiatric disease.
  * Alcohol dependence, alcohol abuse or drug abuse or addiction with any recreational drug within past one year.
  * Clinically significant illness (except ovarian cancer)within 4 weeks before the start of the study v. Positive result to HIV, HCV, RPR and HBsAg.
  * Use of enzyme-modifying drugs (like Phenytoin, Carbamazepine, Barbiturates, Gresiofulvine etc.) in the previous 30 days before day 1 of this study and during the study.
* Donation of 350 mL or more of blood in the previous 90 days before day 1 of this study.
* Participation in another clinical trial within the preceding 90 days of study start
* Subjects who have:

  * Systolic blood pressure less than 90 mm of Hg or more than 140 mm of Hg
  * Diastolic blood pressure less than 60 mm of Hg or more than 90 mm of Hg
  * Pulse rate below 60/min. or above 100/min
C: Inclusion Criteria:

1. Patients with histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer
2. Relapsed disease
3. Patients with up to three prior therapies. In patients with 1 or 2 prior treatment lines, the treatment free interval after platinum has to be less than 6 months; in addition patients with three prior lines of chemotherapy who are not considered for platinum-containing chemotherapy lines are also eligible
4. Measurable disease, evaluable disease in combination with GCIG CA-125 criteria, or histologically proven relapse/progression
5. Mandatory de novo tumor biopsy (not older than 3 months) sent to central laboratory as formalin-fixed, paraffin-embedded (FFPE) sample for determination of PDL1 status prior to randomization for stratification.
6. Availability of a representative archival FFPE tumor sample (preferable from primary diagnosis)
7. Patient has not progressed on the chosen/planned chemotherapy (PLD or Paclitaxel) in any prior line
8. Patients previously treated with bevacizumab are eligible, with the exclusion of those patients that has suspended bevacizumab for more than 2 subsequent cycles or permanently discontinued bevacizumab during their previous treatment due to toxicity.
9. Females aged ≥ 18 years at signing at time of signing informed consent form
10. Signed written informed consent and ability to comply with the study protocol, in the investigator's judgement
11. Adequate hematological, renal and hepatic function within 28 days prior to first administration of study treatment:

    * Hemoglobin ≥ 9.0 g/dL
    * Absolute neutrophil count (ANC) ≥ 1.5 x 10xE\^9/L
    * Platelet count ≥ 100 x 10xE\^9/L
    * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    * Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT) ≤ 2.5 x ULN, unless liver metastases are present, in case of liver metastases values must be ≤ 5 x ULN
    * Serum creatinine ≤ 1.5 x institutional ULN
    * Patient not receiving anticoagulant medication who has an International Normalized Ratio (INR) ≤ 1.5 and an Activated ProThrombin Time (aPTT) ≤ 1.5 x ULN. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to site medical standard). If the patient is on oral anticoagulants, dose has to be stable for at least two weeks at the time of randomization
    * Urine dipstick for proteinuria \< 2+. If urine dipstick is ≥ 2+, 24-hours urine must demonstrate ≤ 1 g of protein in 24 hours.
12. Patients must have adequately controlled blood pressure (BP), with a systolic BP of ≤ 140 mmHg and diastolic BP of ≤ 90 mmHg for eligibility. Patients must have a BP of ≤ 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to starting study.
13. Estimated life expectancy of at least 3 months
14. ECOG performance status 0 - 1
15. Negative urine or serum pregnancy test within 7 days of study treatment in women of childbearing potential (WOCBP), confirmed prior to treatment on day 1
16. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 5 months after administration of the last dose of atezolizumab/placebo and 6 months after the last dose of bevacizumab, paclitaxel, or PLD, whichever is later.
17. For countries where this will apply to: a patient will be eligible for randomization in this study only, if either affiliated to, or a beneficiary of a social security category.
18. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, that include the completion of patient-reported outcomes questionnaires.

Exclusion Criteria:

1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors)
2. Ovarian tumors of low malignant potential (e.g. borderline tumors)
3. Malignancies other than ovarian cancer within 5 years prior to randomisation, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer)
4. More than three prior systemic anticancer regimens; maintenance therapies (e.g. with bevacizumab, olaparib or niraparib) are not calculated as separate line.
5. Prior systemic anticancer therapy within 28 days before randomization (except bevacizumab: 20 days).
6. Prior radiotherapy to the pelvis or the abdomen.
7. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement thera-py is permitted).
8. Prior treatment with anti-CD137 or immune checkpoint blockade therapies, anti-PD1, or anti-PD-L1 therapeutic antibodies or anti-CTLA 4
9. Prior randomization in AGO-OVAR 2.29.
10. Treatment with systemic immunostimulatory agents (in-cluding but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1, day 1.
11. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophos-phamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor \[TNF\] agents) within 2 weeks prior to cycle 1, day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.

    The use of inhaled corticosteroids for chronic obstruc-tive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
12. Patients with a history of allergic reaction to IV contrast requiring steroid pre-treatment should have screening and subsequent tumor assessments performed using magnetic resonance imaging (MRI).
13. Administration of a live, attenuated vaccine within 4 weeks prior to cycle 1, day 1 or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after the last dose of atezolizumab/placebo. Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccination
14. Major surgery within 4 weeks of starting study treatment or patient who has not completely recovered from the effects of any major surgery. Core biopsy or other minor surgical procedure within 7 days prior to day 1, cycle 1 is permitted.
15. Previous allogeneic bone marrow transplant or previous solid organ transplantation.
16. Current treatment with anti-viral therapy for HBV.
17. History of idiopathic pulmonary fibrosis (including pneumonitis), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evi-dence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) detected on screening chest CT scan is permitted
18. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization
19. History or evidence hemorrhagic disorders within 6 months prior to randomization
20. Patients are excluded if having a history or evidence of thrombosis as follows:

    * Any Grade 4 thrombosis
    * Arterial thrombosis within 6 months prior to ran-domization
    * Grade ≤ 3 venous thrombosis within 3 months prior to randomization Patients with central venous access thrombosis are eligi-ble.
21. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of sus-pected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of sus-pected spinal cord compression
22. History of autoimmune disease, including but not limited to dermatomyositis, myasthenia gravis, myositis, auto-immune hepatitis, systemic lupus erythematosus, rheu-matoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guil-lain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Except patients with:

    * a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone
    * controlled type 1 diabetes mellitus on a stable insulin regimen

    Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
    * Rash must cover \< 10% of body surface area
    * Disease is well controlled at baseline and requires only low-potency topical corticosteroids
    * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
23. Any prior history of hypertensive crisis (CTCAE grade 4) or hypertensive encephalopathy.
24. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV), patients with active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C.

    Patients with past hepatitis B virus (HBV) infection or re-solved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
25. Persistent toxicities (≥ CTCAE grade 2) with the exception of alopecia, caused by previous cancer treatment. Neurotoxicity CTCAE grade 2 is permitted in case the patient is planned for PLD treatment.
26. Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomization, including but not limited to active tuberculosis or hospitalization for complications of infection, bacteremia, or severe pneumonia. Patients receiving prophylactic antibiotics (e.g., to prevent urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
27. Current or recent (within 10 days prior randomization) chronic use of aspirin \> 325 mg/day.
28. Clinically significant (e.g. active) cardiovascular disease, including:

    * Myocardial infarction or unstable angina pectoris within ≤ 6 months of randomization
    * New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF)
    * Poorly controlled cardiac arrhythmia despite medica-tion (patients with rate controlled atrial fibrillation are eligible)
    * Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living \[ADL\] requiring repair or revision)
    * Resting ECG with QTc \>470 msec or family history of long QT syndrome
29. For patients with PLD treatment: Left ventricular ejection fraction defined by ECHO below the institutional lower limit of normal
30. Evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation).
31. Non-healing wound, active ulcer or bone fracture.
32. History of bowel obstruction (including subocclusive disease) related to underlying disease, a history of ab-dominal fistula, GI perforation, or intra-abdominal abscess, or evidence of deep infiltration of the bowel by pelvic examination or on computed tomography, or clinical symptoms of bowel obstruction.
33. Patients with evidence of abdominal free air.
34. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications
35. Known hypersensitivity or allergy to drugs containing Chinese hamster (CHO) ovary cells or history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
36. Known hypersensitivity reaction or allergy to drugs chemically related to bevacizumab, paclitaxel, pegylated liposomal doxorubicin, or their excipients that contra-indicates the subject's participation.
37. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. This includes also any psychiatric disorder that prohibits obtaining informed consent.
38. Pregnancy, lactation, or intention to become pregnant during the study or within 5 months after the last dose of atezolizumab/placebo as well as breastfeeding women or intended to breastfeed during the study and up to 6 months after treatment with paclitaxel, bevacizumab and pegylated liposomal doxorubicin (PLD).
39. For France only: Patients deprived of their liberty by judicial or administrative decision and patients under a legal protection measure or unable to express their consent.
D: Inclusion Criteria:

1. Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
2. Patients with the following histologic cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor or adenocarcinoma not otherwise specified.
3. Patient must have measurable disease as defined by RECIST 1.1.
4. Patients must have received treatment with a platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment.

   Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease.

   Patients are allowed to have received, but are not required to have received, biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their primary treatment regimen or for management of recurrent or persistent disease.
5. Patients must have platinum-resistant disease, defined as having a platinum-free interval (PFI) of \< 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy.
6. Patients must have adequate bone marrow, renal, hepatic, and neurologic functions as defined by the following:

   * Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3. This ANC cannot have been induced or supported by granulocyte colony stimulating factors. Platelets ≥ 100,000/mm3. Hemoglobin ≥ 9 g/dL.
   * Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN).
   * Hepatic function: bilirubin \< 1.2 mg/dL, SGOT (AST) and SGPT (ALT) ≤ 3.0 x ULN and alkaline phosphatase ≤ 2.5 x ULN.
7. Patients must have recovered from effects of recent surgery, radiotherapy or chemotherapy:

   * Patients should be free of active infection requiring parenteral antibiotics.
   * Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted.
   * Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents and immunologic agents, must be discontinued at least three weeks prior to registration.
   * Any prior radiation therapy must be completed at least four weeks prior to registration.
8. Patients must have a GOG performance status of 0 or 1.
9. Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to study entry.
10. Patients must meet the entry requirements and undergo the baseline procedures.
11. Patients must have signed an IRB-approved informed consent form and authorization permitting release of personal health information.

Exclusion Criteria:

1. Patients who have had treatment with VTX-2337, doxorubicin, PLD, or any other anthracycline.
2. Patients who have received an investigational agent \< 30 days prior to registration.
3. Patients who have received oral or parenteral corticosteroids \< 2 weeks prior to registration or who require ongoing systemic immunosuppressive therapy for any reason.
4. Patients with active autoimmune disease. "Active" refers to any condition currently requiring therapy. Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis.
5. Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of the other malignancy being present within the last three years.
6. Patients who have received prior radiotherapy OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years are excluded.
7. Patients who have received prior chemotherapy OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years are excluded.
8. Patients with history or evidence upon physical examination of 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.
9. Patients with clinically significant cardiovascular disease.
10. Patients who are pregnant or nursing.
11. Patients under the age of 18.
12. Patients with clinical symptoms or signs of gastrointestinal obstruction and/or who require parenteral hydration or nutrition.

Answer: D