Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Phase II/III Study of Pegylated Liposomal Doxorubicin and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin, CTEP-Supplied Bevacizumab and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin and CTEP-Supplied Bevacizumab in Platinum Resistant Ovarian Cancer
Brief Summary: This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent). Chemotherapy drugs, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. It is not yet known which combination will work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.


Options:
A: Inclusion Criteria:

* Patient must have epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Patients must have received ≥2 and not more than 5 prior therapies, including at least 1 line of therapy containing bevacizumab (or biosimilar).
* Patients must be considered platinum-resistant, defined as progression within 6 months from completion of a platinum-containing therapy
* Patient must be considered appropriate for treatment with weekly paclitaxel monotherapy as the next line of therapy.
* Patient must be willing and able to provide an FFPE archival or core tumor sample for determination of biomarker status on the Xerna™ TME Panel biomarker assay (positive or negative) prior to study treatment.
* Presence of at least one measurable lesion, as defined by RECIST v1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 Adequate organ function

Exclusion Criteria:

* Non-epithelial ovarian carcinoma.
* Ovarian tumors with low malignant potential (i.e., borderline tumors).
* Primary platinum-refractory disease (defined as progression during or within 4 weeks after completion of the first platinum regimen).
* Patient has received an anti-angiogenic product other than bevacizumab or biosimilar.
* Patient has congestive heart failure
* Patient has a history of myocardial infarction, cerebral vascular accident, or transient ischemic attacks within 6 months
* Patient has a history of cardiac ischemia or heart failure within 6 months
* Baseline B-type natriuretic peptide (BNP) value \>100 pg/mL or N-terminal-proBNP (NT-proBNP) value of \> 125 pg/mL.
* LVEF \<50%.
* Peak tricuspid velocity \>3.0 m/s on Doppler ECHO.
* Clinically significant ECG abnormality, as assessed by the investigator
* Blood pressure (BP) \>140/90 mmHg
* History of bowel obstruction, including sub-occlusive disease, related to the underlying disease
* Hemoptysis \>2.5 mL within 8 weeks prior
* Major surgical procedure, or significant traumatic injury within 28 days
* Uncontrolled seizure disorder or active neurologic disease
* Patients with a cardiac aneurysm.
B: Inclusion Criteria:

* Patients must have platinum-resistant/refractory (i.e., platinum-free interval \<6 months) recurrent or persistent histologically confirmed epithelial (non-mucinous) ovarian, fallopian tube, or primary peritoneal cancer.

Patients may have serous, endometrioid, clear cell, carcinosarcoma, or transitional cell/malignant Brenner, mixed, or undifferentiated histologies.

* Patients must have specimen available for immunohistochemistry for class III β-tubulin status; recurrent tumor specimen is preferred, though this may be performed on primary tumor if no recurrent tumor is available.
* All patients must have measurable disease. Measurable disease is defined as lesions that can be measured by physical examination or by means of medical imaging techniques. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation or plain x-ray, or ≥ 10 mm when measured by spiral CT and/or MRI. Ascites and pleural effusions are not to be considered measurable disease.
* Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST v1.1 Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
* At the time of initial surgery, patients may have been optimally (\<1 cm diameter residual disease) or sub-optimally (≥1 cm diameter of residual disease) debulked.
* Patients with measurable recurrent disease of any previous stage (I-IV) are eligible to enrollment.
* The diagnosis must be histologically confirmed by a gynecologic pathologist.
* Patients must have adequate bone marrow, kidney, and liver function:

  1. Absolute neutrophil count greater than or equal to 1500 cells/mm3
  2. Platelets greater than or equal to 100,000/uL
  3. Renal function: creatinine less than or equal to 2.0 mg/dL
  4. Hepatic function: Bilirubin ≤ 1.5 X laboratory normal
  5. SGOT/SGPT ≤ 3 X laboratory normal.
* Patients must have an ECOG performance status of 0-2.
* Patients must have signed an approved informed consent.
* Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy. They should be free of significant infection.
* Patients must have received prior treatment with taxanes. There is no limit on the number of prior lines of therapy.
* Patients may have received prior bevacizumab therapy alone or in combination with chemotherapy. A 3-week washout period is required.
* Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the study entry and be practicing an effective form of contraception (section 7.5.3).
* Patients must be at least 18 years of age.

Exclusion Criteria:

* Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers, are excluded if there is any evidence of other malignancy present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
* Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure, or uncontrolled arrhythmias within 6 months of registration (NYHA classification III-IV).
* Patients with any unstable medical issue (including cardiac issues as above, active treatment for symptomatic pulmonary embolism, CVA, renal or hepatic insufficiency, active infection/sepsis requiring intravenous antibiotics). In patients who have undergone surgery, 28 days should elapse before initiation and the surgical site should be adequately healed.
* Known brain/leptomeningeal involvement of the disease, active neurological disease such as uncontrolled seizure disorder or moderate to severe dementia.
* Patients who have received prior therapy with any covalent irreversible anti-angiogenic tyrosine kinase inhibitor (e.g., vandetanib).
* Patients known to be seropositive for human immunodeficiency virus (HIV) and active hepatitis, even if liver function studies are in the eligible range.
* Known hemorrhagic diathesis or active bleeding disorder, including platelet count \<100,000/uL, or inadequate granulocytes, including an absolute neutrophil count \<1500 cells/mm.
* Any hypersensitivity to Cremophor® EL or polyoxyethylated castor oil.
* CTCAE grade 2 or higher peripheral neuropathy.
C: Inclusion Criteria:

* Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
* Administration of study drugs (pegylated liposomal doxorubicin, bevacizumab, atezolizumab) may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. (06/29/2017)
* Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial
* High grade ovarian cancer, including high grade serous; clear cell; endometrioid, grade 3; and others (adenocarcinoma, not otherwise specified \[NOS\]; mixed epithelial carcinoma; undifferentiated carcinoma); NOTE: low grade serous, mucinous and carcinosarcoma histologies are excluded due to their different underlying genomic features and/or clinical behavior; ovarian cancer = ovarian, fallopian tube or primary peritoneal cancer; required data element: submission of pathology report
* Recurrent, platinum resistant ovarian cancer (defined as progression within \< 6 months from completion of platinum based therapy; the date should be calculated from the last administered dose of platinum therapy)
* 1-2 prior regimens (including primary therapy); hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit; PARP inhibitors given in the maintenance setting post response to platinum-based therapy will not count as a separate regimen from the preceding platinum-based therapy. (30-OCT-2020)
* Measurable disease (defined by RECIST v1.1) or evaluable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease related in the setting of cancer antigen \[CA\] 125 \>= 2 x upper limit of normal \[ULN\])
* Age \>= 18
* Performance status 0, 1 or 2
* Absolute neutrophil count (ANC) \>= 1,500/mcl (within 14 days prior to registration)
* Platelets \>= 100,000/mcl (within 14 days prior to registration)
* Hemoglobin (Hgb) \>= 8 g/dl (within 14 days prior to registration)
* Creatinine =\< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
* Urine protein creatinine (UPC) ratio must be \< 1.0 (within 14 days prior to registration); if UPC ratio \>= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be \< 1000 mg for patient enrollment); If UPC ratio cannot be calculated because the urine protein is below the lower limit of detection of the assay this will not exclude the patient (10/22/2018) (30-OCT-2020); UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
* Total bilirubin =\< 1.5 x ULN (patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled) (within 14 days prior to registration)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement) (within 14 days prior to registration)
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (or on stable dose of therapeutic anticoagulation, such as low-molecular-weight heparin, warfarin or rivaroxaban) (10/16/2017)
* Thyroid-stimulating hormone (TSH) within normal limits (Euthyroid patients on thyroid replacement therapy allowed provided TSH \< ULN) (02/20/2019)
* The patient or legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

* Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
* Patients who have had systemic anticancer therapy (e.g., chemotherapy, targeted therapy including PARP inhibitors or bevacizumab) within 3 weeks prior to entering the study (30-OCT-2020)
* Patients who have had hormonal therapy (e.g., tamoxifen, aromatase inhibitor) within 1 week prior to entering the study
* Patients with prior treatment with anti-programmed cell death (PD)-1, anti- programmed cell death ligand (PD-L)1 or anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 therapeutic antibody or other similar agents (10/16/2017)
* Patients with prior treatment with bevacizumab (or any other anti vascular therapy, e.g., cediranib) for platinum resistant recurrence; (Note: prior bevacizumab in initial therapy and/or platinum sensitive recurrent setting is allowed) (10/16/2017)
* Patients with prior treatment with PLD
* Prior radiotherapy to the abdomen or pelvis
* Patients who have not recovered from adverse events to =\< grade 1 (other than alopecia) due to agents administered more than 3 weeks earlier (10/16/2017); however, the following therapies are allowed:

  * Hormone replacement therapy or oral contraceptives
  * Herbal therapy \> 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
  * Palliative radiotherapy for bone metastases \> 2 weeks prior to cycle 1, day 1
* Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 6 weeks prior to cycle 1, day 1
* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1

  * Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or steroids as computed tomography \[CT\] scan contrast premedication) may be enrolled
  * The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
* Patients taking bisphosphonate therapy for symptomatic hypercalcemia within the past 28 days; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
* Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:

  * Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:

    * Evaluable or measurable disease outside the CNS
    * No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
    * No history of intracranial hemorrhage or spinal cord hemorrhage
    * No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
    * No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1
  * Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:

    * Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
    * No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1
    * Screening CNS radiographic study \>= 4 weeks from completion of radiotherapy and \>= 2 weeks from discontinuation of corticosteroids
* Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Patients requiring treatment with a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumab
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease

  * Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible
  * Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
* History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis (02/20/2019)

  * Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
  * Patients with controlled type 1 diabetes mellitus on a stable insulin regimen, or type 2 diabetes mellitus are eligible
  * Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:

    * Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
    * Rash must cover less than 10% of body surface area (BSA)
    * Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
    * No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
* History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Patients with active tuberculosis (TB) are excluded
* Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
* Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
* Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study
* Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab (06/29/2017)

  * Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks prior to cycle 1, day 1 or at any time during the study
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial (08-JAN-2021)
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years, with the exception of those with a negligible risk of metastases or death, such as carcinoma in situ of the breast or cervix
* Severe, active co-morbidity defined as follows:

  * Current (within 28 days of cycle 1, day 1) signs and/or symptoms of bowel obstruction
  * Patients who require parental hydration and/or nutrition
  * Patients who require drainage gastrostomy tube
  * Evidence of bleeding diathesis or clinically significant coagulopathy
  * Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture
  * History of hemoptysis (\>= 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment
* Significant cardiovascular or cerebrovascular disease including:

  * Uncontrolled hypertension (systolic blood pressure \[SBP\] \>= 150 and/or diastolic blood pressure \[DBP\] \>= 90)
  * History of myocardial infarction within 6 months
  * Unstable angina
  * New York Heart Association functional classification II, III or IV
  * Baseline ejection fraction =\< 50% as assessed by echocardiogram or multi-gated acquisition (MUGA)
  * Cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6 months
  * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or peripheral arterial thrombosis) within 6 months
* History of abdominal/pelvic or tracheoesophageal fistula or gastrointestinal perforation and/or abdominal/pelvic abscess within 6 months prior to initiation of treatment (02/20/2019)
* Pregnant or lactating patients
D: Inclusion Criteria:

1. Age ≥18 years, female;
2. Recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer proven to be platinum-resistant by histology or cytology;
3. ECOG score was 0-1;
4. Expected survival time \> 12 weeks;
5. Normal or abnormal bone marrow, kidney, and liver function of the patient has no clinical significance, and the specific situation will be comprehensively determined by the investigator;
6. Patients not previously treated with PARPi or targeted drugs;
7. The patient has taken effective contraceptive measures within 14 days prior to screening and is willing to sign the notification until the last medication No pregnancy plan and voluntary use of effective contraceptive measures within the next 6 months;
8. The subject or his/her legal guardian can communicate well with the investigator, understand and comply with the requirements of this study, and understand and sign the informed consent.

Exclusion Criteria:

1. Known allergy to fluzopalil or study drug components;
2. Patients with any factors affecting oral administration (such as previous gastric or small bowel resection, or current atrophic gastritis, chronic intestinal disease, gastrointestinal bleeding, dysphagia, gastrointestinal obstruction, or diarrhea greater than grade 1, including those who have recovered but have not recovered);
3. Patients who underwent major surgery or gastrointestinal surgery affecting drug absorption, open biopsy, severe traumatic injury, wound unhealed or did not recover from major surgery within 1 month before the trial;
4. Before the first administration, patients have used strong CYP3A inhibitors (such as itraconazole, telithromycin, clarithromycin, ritonavir, etc.) or medium CYP3A inhibitors (such as ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil, etc.); Patients who had used strong CYP3A inducers (e.g., phenobarbide, enzyluamide, phenytoin, rifampicin, rifambutin, rifapentine, carbamazepine, nevirapine and St. John's herb) or medium CYP3A inducers (e.g., Bosentan, efavirenz, modafinil, etc.) and did not reach 3 elimination half-lives;
5. Pregnant or lactating women or subjects who cannot use contraception as required;
6. Those who have special requirements on diet and cannot accept uniform diet;
7. As judged by the researcher, there are other circumstances that are not suitable for the researcher.

Answer: C