Please select the eligibility criteria that correspond to the clinical trial below.
Title: An International Phase 3 Randomized Trial of Autologous Dendritic Cell Immunotherapy (AGS-003) Plus Standard Treatment of Advanced Renal Cell Carcinoma (ADAPT)
Brief Summary: This is a trial of AGS-003, which is being studied as a possible treatment for Advanced Renal Cell Carcinoma. The purpose of this study is to determine whether there is an overall survival (OS) benefit between subjects treated with AGS-003 in combination with standard treatment versus subjects treated with standard treatment alone.


Options:
A: Inclusion Criteria:

* Advanced kidney cancer

Exclusion Criteria:

* Previous treatment for kidney cancer, except surgical removal of kidney tumor
B: Inclusion Criteria:

1. Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell component.
2. Measurable disease by RECIST criteria.
3. Age \>/= 18 years
4. ECOG performance status 0-2 or Karnofsky Performance Status \>/= 60%
5. Meets criteria for poor-risk defined as 3 or more of the following: ECOG performance status 2, anemia (hemoglobin lower than reference range), elevated serum LDH \> 1.5x upper limit of normal (ULN), hypercalcemia (corrected serum calcium level \> upper limit of normal), time from initial RCC diagnosis to registration on this trial \< 1 year, and \> 1 metastatic organ sites.
6. Adequate organ and marrow function within 14 days of registration as defined below: a) Absolute neutrophil count \>/=1,500/µL b) Platelets \>/=100,000/µL c) Hgb \>/= 9.0 g/dL (transfusion allowed) d) Renal: serum creatinine \</= 1.5 x ULN or calculated CrCl \>/= 40 cc/min and random urine protein:creatinine ratio (UPC) \< 1 or 24-hr urine protein \< 1g e) Liver: total bilirubin \</= 1.5 mg/dl; AST (SGOT) and ALT (SGPT) \</= 2.5 x ULN for subjects without evidence of liver metastases, \</= 5 x ULN for subjects with documented liver metastases f) INR \</= 1.2 x ULN; PTT \</= 1.5 x ULN. Therapeutic anticoagulation with warfarin is allowed if target INR \</= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for \> 2 weeks (14 days) at time of randomization.
7. Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days of study registration. Pregnancy test must be repeated if performed \> 14 days before starting study drug.

Exclusion Criteria:

1. Prior malignancy, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 2 years
2. Prior targeted therapy (anti-VEGF agents or mTOR inhibitors) including adjuvant therapy, and prior chemotherapy for mRCC. However, prior immunotherapy (cytokines or vaccines) is allowed.
3. Any experimental drug while on this study; however, concomitant bone targeted therapy (bisphosphonates or the anti-RANK ligand denosumab) is allowed.
4. Uncontrolled brain metastases and infections. Patients with brain metastases treated with Gamma Knife (GK) or whole brain radiation within 24 hours of registration.
5. History of stroke within 6 months of registration
6. Clinically significant cardiovascular disease, defined as myocardial infarction (or unstable angina) within 6 months of registration, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management. However, treated and controlled or stable/not clinically significant cardiovascular disease is allowed per evaluation by cardiologist.
7. Uncontrolled hypertension (home blood pressure readings are permitted) or prior history of hypertensive crisis or hypertensive encephalopathy; however, treatment of hypertension with medications is permitted.
8. History of uncontrolled hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
9. Significant vascular disease including aortic aneurysm, aortic dissection.
10. Symptomatic peripheral vascular disease
11. Pregnancy
12. HIV-positive patients receiving combination anti-retroviral therapy
13. Coagulopathy or bleeding diathesis
14. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)
15. Major surgery within 28 days prior to registration
16. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device within 7 days prior to starting drug
17. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration
18. Serious non-healing wound
19. Baseline QTcB \>/= 470 msec.
C: Inclusion Criteria:

1. Signed written informed consent
2. Patient must be willing and able to comply with the protocol.
3. Age ≥ 18 years.
4. Histologic og cytologic biopsy proven locally advanced or metastatic renal cell carcinoma, considered non-candidates for curative surgery. Nephrectomy is not mandatory.
5. Patient with renal cell carcinoma (RCC) with a clear-cell histologic component confirmed by local pathology review.
6. Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded
7. Fertile women of childbearing potential (\<2 years after last menstruation) and men must use effective means of contraception
8. Memorial-Sloan-Kettering-Cancer-Centre favourable- and intermediate prognostic group.
9. Measurable or non-measurable disease (as per RECIST1.1 criteria)
10. Karnofsky Performance status of 70% or higher.
11. Life expectancy greater than 4 months.
12. The required laboratory values at baseline are as follows:

Haematology:

WCC ≥ 3.0 x 109/L, Platelet count ≥ 100 x 109/L, Haemoglobin ≥ 6.2 mmol/l, (INR) ≤ 1.5, APTT ≤ 1.5 x ULN

Biochemistry:

Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST, ALT ≤ 2.5 x ULN in patients without liver metastases, ≤ 5 x ULN in patients with liver metastases, Serum Creatinine ≤ 150 micromol/L

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Exclusion Criteria:

1. Prior systemic treatment for metastatic RCC disease
2. Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to randomization.
3. Serious non-healing wound, ulcer or bone fracture.
4. Evidence of current central nervous system (CNS) metastases or spinal cord compression. Patient must undergo an MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to randomization.
5. Seizure(s) not controlled with standard medical therapy.
6. Dipstick urine test of protein ≥ 2+.
7. Other malignancies within 5 years prior to randomization (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
8. Evidence of bleeding diathesis or coagulopathy.
9. Ongoing or recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral anticoagulants or chronic daily treatment with aspirin. Low molecular weight heparin are allowed
10. Uncontrolled hypertension (≥ 160 mm Hg systolic and/or ≥ 100 mm Hg diastolic) while receiving chronic medication.
11. Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months before randomisation), myocardial infarction (≤ 6 months before randomisation), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
12. Recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
13. Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent), excluding inhaled steroids.
14. History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications.
15. Known hypersensitivity to interleukin-2, Interferon, alfa or bevacizumab.

Serial blood test, serial tumor biopsies and serial dynamic contrast-enhanced imaging will be obtained as part of a translational research program integrated in the clinical trial.

Part(s) of the translational research program may be omitted in the individual patient due to practical, technical or safety reasons, without having consequences for participating in the additional translational research investigations or the clinical part of the study.

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D: Key Inclusion Criteria for Tumor Collection:

1. Diagnosis or clinical signs of advanced RCC
2. Scheduled for cytoreductive or partial nephrectomy

Key Exclusion Criteria for Tumor Collection:

1. Known inability to undergo sunitinib treatment as currently labeled, due to pre-existing medical conditions
2. Requirement for systemic chronic immunosuppressive drugs or corticosteroids
3. Evidence of brain metastases prior to nephrectomy

Key Inclusion Criteria for Treatment Study:

1. Advanced disease, histologically assessed as RCC, with predominantly clear cell histology
2. Metastatic disease (measurable or non-measurable) that can be monitored throughout the course of the study participation per RECIST 1.1
3. Subjects who are candidates for standard first-line therapy initiating with sunitinib
4. Time from diagnosis to treatment \< 1 year
5. Karnofsky performance status (KPS) ≥ 70%
6. Life expectancy of 6 months or greater
7. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to Grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
8. Adequate hematologic, renal, hepatic, and coagulation function
9. Negative serum pregnancy test for female subjects with reproductive potential, and agreement of all male and female subjects of reproductive potential to use a reliable form of contraception during the study and for 12 weeks after the last dose of study drug
10. Normal ECG or clinically non-significant finding(s) at Screening
11. Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study
12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Key Exclusion Criteria for Treatment Study:

1. Prior systemic therapy (including adjuvant or neoadjuvant) of any kind for RCC, including immunotherapy, chemotherapy, hormonal, or investigational therapy
2. Prior history of malignancy within the preceding 3 years, except for adequately treated in situ carcinomas or non-melanoma skin cancer, adequately treated early stage breast cancer, superficial bladder cancer, and non-metastatic prostate cancer with a normal PSA
3. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease
4. Patients with 4 or more of the following risk factors:

   1. Hgb \< LLN
   2. Corrected calcium \> 10.0 mg/dL
   3. KPS \< 80%
   4. Neutrophils \> ULN
   5. Platelets \> ULN
5. Planned or elective surgical treatment post-nephrectomy for the direct management of RCC, within 28 days before Visit 1 (Week 0)
6. NCI CTCAE Grade 3 hemorrhage \< 28 days before Visit 1 (Day 0)
7. Clinically significant cardiovascular conditions within 3 months prior to Randomization
8. Significant gastrointestinal abnormalities
9. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
10. Active autoimmune disease or condition requiring chronic immunosuppressive therapy
11. Clinically significant infections, including human immunodeficiency virus, syphilis, and active hepatitis B or C
12. Current treatment with an investigational therapy on another clinical trial
13. Pregnancy or breastfeeding
14. Any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment

Answer: D