Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3 Randomized Study of TLK286 (Telcyta®) in Combination With Liposomal Doxorubicin (Doxil/Caelyx)Versus Liposomal Doxorubicin (Doxil/Caelyx) as Second-Line Therapy in Platinum Refractory or Resistant Ovarian Cancer (ASSIST-5)
Brief Summary: The purpose of this research study is to determine if Telcyta® given in combination with liposomal doxorubicin is more effective than liposomal doxorubicin alone in treating women who have recurrent ovarian epithelial cancer, fallopian tube cancer or primary peritoneal cancer that is refractory or resistant to platinum chemotherapy.


Options:
A: Inclusion Criteria:

* Are a woman 18 years of age or older
* Have histologically or cytologically confirmed epithelial cancer or primary peritoneal cancer
* Have platinum refractory or resistant cancer
* Measurable disease according to radiographic RECIST criteria progression

Exclusion Criteria:

* Had treatment with first-line chemotherapy other than a platinum-containing regimen
* Have clinically significant cardiac disease
* Have any sign of intestinal obstruction interfering with nutrition
* Are pregnant or lactating
* Had prior treatment with liposomal doxorubicin
* Had prior treatment with Telcyta
B: Inclusion Criteria:

* Signed written informed consent obtained prior to initiation of any study specific procedures and treatment as confirmation of the patients awareness and willingness to comply with the study requirements
* Primary diagnosis is confirmed by specialized pathology review (Germany only)
* Females aged ≥ 18 years
* Histologically confirmed, newly diagnosed

  * Epithelial ovarian carcinoma
  * Fallopian tube carcinoma
  * Primary peritoneal carcinoma AND FIGO stage IIb - IV (all grades and all histological types)
* Patients should have already undergone surgical debulking, by a surgeon experienced in the management of ovarian cancer, with the aim of maximal surgical cytoreduction according to the GCIG Conference Consensus Statement. There must be no planned surgical debulking prior to disease progression. Patients with stage III and IV disease in whom initial surgical debulking was not appropriate or possible will still be eligible providing

  * the patient has a histological diagnosis and
  * debulking surgery prior to disease progression is not foreseen
* Patients must be able to commence cytotoxic chemotherapy within 8 weeks of cytoreductive surgery. The first dose of bevacizumab can be omitted in both arms if the investigator decides to start chemotherapy within 4 weeks of surgery.
* ECOG 0-2
* Life expectancy \> 3 months
* Adequate bone marrow function (within 14 days prior to randomization)

  * ANC ≥ 1.5 x 10\^9/L
  * PLT ≥ 100 x 10\^9/L
  * Hb ≥ 9 g/dL (can be post-transfusion)
* Adequate coagulation parameters (within 14 days prior to randomization)

  * Patients not receiving anticoagulant medication who have an INR ≤ 1.5 and an aPTT ≤ 1.5 x ULN
  * The use of full-dose oral or par-enteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to institution medical standard) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization.
* Adequate liver function (within 14 days prior to randomization)

  * Serum bilirubin ≤ 1.5 x ULN
  * Serum transaminases ≤ 2.5 x ULN
* Urine dipstick for proteinuria \< 2+. If urine dipstick is ≥ 2+, 24 hour urine must demonstrate ≤ 1 g of protein in 24 hours
* Adequate postoperative GFR \> 40 ml/min (estimates based on the Cockroft-Gault or Jelliffe formula are sufficient)

Exclusion Criteria:

* Non-epithelial origin of the ovary, the fallopian tube or the peritoneum
* Borderline tumours (tumours of low malignant potential) and FIGO stage Ia - IIa tumours
* Planned intraperitoneal cytotoxic chemotherapy
* Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
* Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for the fact that bevacizumab can be omitted from the first cycle of chemotherapy). It is strongly recommended that an interval of 7 days is left between the insertion of any central venous access devices (CVADs) and the onset of bevacizumab treatment.
* Any planned surgery during the study treatment period plus 4 additional weeks to allow for bevacizumab clearance
* Uncontrolled hypertension (sustained elevation of BP systolic \> 150mmHg and/or diastolic \> 100mmHg despite antihypertensive therapy)
* Any previous radiotherapy to the abdomen or pelvis
* Significant traumatic injury during 4 weeks preceding the potential first dose of bevacizumab
* 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 suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.
* History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy e.g. uncontrolled seizures
* Previous Cerebro-Vascular Accident (CVA), Transient Ischaemic Attack (TIA) or Sub-Arachnoid Haemorrhage (SAH) within 6 months prior to randomization
* Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least 6 months afterwards
* Pregnant or lactating women
* Treatment with other investigational agents, or participation in another clinical trial testing a drug within the past 4 weeks before start of therapy concomitantly with this trial
* Malignancies other than ovarian cancer within 5 years prior to randomization, except for adequately treated

  * carcinoma in situ of the cervix
  * and/or basal cell skin cancer
  * and/or non-melanomatous skin cancer
  * carcinoma in situ of the breast
  * and/or early endometrial carcinoma as specified below. Patients may have received previous adjuvant chemotherapy for other malignancies e.g. breast or colorectal carcinoma if diagnosed over 5 years ago with no evidence of subsequent recurrence.
* Patients with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met

  * Disease stage FIGO stage ≤ IA (tumour invades less than one half of the myometrium)
* Known hypersensitivity to bevacizumab and its excipients, Chinese hamster ovary cell products or other recombinant human or humanised antibodies
* Non healing wound, active ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3 weekly wound examinations
* History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to randomization
* Clinically significant cardiovascular disease, including

  * Myocardial infarction or unstable angina within 6 months of randomization
  * NYHA ≥ Grade 2 Congestive Heart Failure (CHF)
  * Poorly controlled cardiac arrhythmia despite medication (patients with rate-controlled atrial fibrillation are eligible)
  * Grade ≥ 3 peripheral vascular disease (i.e. symptomatic and interfering with activities of daily living requiring repair or revision)
* Current or recent (within 10 days prior to randomization) chronic use of aspirin \> 325 mg/day
* Pre-existing sensory or motor neuropathy ≥ Grade 2
* Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
C: Inclusion Criteria:

1. Female participants ≥ 18 years of age
2. Participants must have a confirmed diagnosis of high-grade serious epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
3. Participants must have platinum-resistant disease:

   1. Participants who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between \>3 months and ≤ 6 months after the date of the last dose of platinum
   2. Participants who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression. Note: Participants who are platinum-refractory during front-line treatment are excluded
4. Participants must have progressed radiographically on or after their most recent line of therapy
5. Participants must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity
6. Participant's tumor must be positive for FRα expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay
7. Participants must have at least one lesion that meets the definition of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (radiologically measured by the Investigator)
8. Participants must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment:

   1. Adjuvant ± neoadjuvant considered one line of therapy
   2. Maintenance therapy (for example, bevacizumab, poly (ADP-ribose) polymerase \[PARP\] inhibitors) will be considered as part of the preceding line of therapy (that is, not counted independently)
   3. Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (that is, not counted independently)
   4. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
9. Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
10. Time from prior therapy:

    1. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
    2. Focal radiation completed at least 2 weeks prior to first dose of study drug
11. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities
12. Major surgery must be completed at least 4 weeks prior to first dose and have recovered or stabilized from the side effects of prior surgery
13. Participants must have adequate hematologic, liver and kidney functions defined as:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/liter (L) (1,500/microliter \[μL\]) without granulocyte colony-stimulating factor (G-CSF) in the prior 10 days or long-acting white blood cell (WBC) growth factors in the prior 20 days
    2. Platelet count ≥ 100 x 10\^9/L (100,000/μL) without platelet transfusion in the prior 10 days
    3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
    6. Serum bilirubin ≤ 1.5 x ULN (participants with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 x ULN
    7. Serum albumin ≥ 2 grams (g)/deciliter (dL)
14. Participants or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) while on study drug and for at least 3 months after the last dose of MIRV or at least 6 months after the last dose of paclitaxel, pegylated liposomal doxorubicin, or topotecan
16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug

Exclusion Criteria:

1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade or borderline ovarian tumor
2. Participants with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy
3. Participants with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
4. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
5. Participants with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and /or monocular vision
6. Participants with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:

   1. Active hepatitis B or C infection (whether or not on active antiviral therapy)
   2. Human immunodeficiency virus (HIV) infection
   3. Active cytomegalovirus infection
   4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study drug Note: Testing at screening is not required for the above infections unless clinically indicated
7. Participants with history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
8. Participants with clinically significant cardiac disease including, but not limited to, any one of the following:

   1. Myocardial infarction ≤ 6 months prior to first dose
   2. Unstable angina pectoris
   3. Uncontrolled congestive heart failure (New York Heart Association \> class II)
   4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
   5. Uncontrolled cardiac arrhythmias
9. Participants assigned to PLD stratum only: Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan
10. Participants with a history of hemorrhagic or ischemic stroke within six months prior to randomization
11. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C)
12. Participants with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis
13. Participants with required use of folate-containing supplements (for example, folate deficiency)
14. Participants with prior hypersensitivity to monoclonal antibodies
15. Women who are pregnant or lactating
16. Participants with prior treatment with MIRV or other FRα-targeting agents
17. Participants with untreated or symptomatic central nervous system (CNS) metastases
18. Participants with a history of other malignancy within 3 years prior to randomization. Note: does not include tumors with a negligible risk for metastasis or death (for example, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients
20. People who are detained through a court or administrative decision, receiving psychiatric care against their will, adults who are the subject of a legal protection order (under tutorship/curatorship), people who are unable to express their consent, and people who are subject to a legal guardianship order
21. Simultaneous participation in another research study, in countries or localities where this is the health authority guidance
D: Inclusion Criteria:

* Signed Informed Consent Form
* Age ≥ 18 years
* Documented ovarian, primary peritoneal, or fallopian tube carcinoma that has recurred
* No prior chemotherapy in the recurrent setting
* Measurable disease
* Recovered from prior radiation therapy or surgery

Exclusion Criteria:

* Prior chemotherapy treatment for recurrent ovarian, primary peritoneal, or fallopian tube carcinoma
* History of abdominal fistula, gastrointestinal perforation (GIP), or intra-abdominal abscess
* Patients with clinical symptoms or signs of gastrointestinal (GI) obstruction or who require parenteral hydration, parenteral nutrition, or tube feeding
* Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure
* Current, recent, or planned participation in an experimental drug study
* History of systemic bevacizumab (Avastin) or other vascular endothelial growth factor (VEGF) or VEGF receptor-targeted agent use
* Inadequately controlled hypertension
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association Class II or greater congestive heart failure (CHF)
* History of myocardial infarction or unstable angina
* History of stroke or transient ischemic attack (TIA)
* Known central nervous system (CNS) disease except for treated brain metastasis
* Significant vascular disease or recent peripheral arterial thrombosis
* History of hemoptysis
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

Answer: A