Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adjuvant Treatment of Resectable Cholangiocellular Carcinoma (CCC) With Cisplatin Plus Gemcitabine. A Prospective Single Center Phase Ib-II Study.
Brief Summary: OBJECTIVES

Primary objective:

The primary objective of the trial is to determine the safety of adjuvant treatment with cisplatin plus gemcitabine for a period of 6 months after curative resection of cholangiocellular carcinoma

Secondary objectives:

Secondary objectives of the trial are to assess the feasibility and efficacy of the adjuvant therapy and to determine duration of response and patterns of failure compared to historical controls without postoperative treatment

Exploratory objectives:

To obtain blood samples and tumor tissue after resection for establishment and characterization of new cholangiocarcinoma cell lines and tumor antigens. Other aims are identification of tumor specific antibodies from blood samples, and characterization of tumor antigens with consecutive development of new specific immunological therapies, e.g. cancer-testis antigens (CTA) for tumor vaccination.

* Trial with medicinal product


Options:
A: Inclusion criteria

1. Histologically or cytologically confirmed adenocarcinoma of biliary tract (intrahepatic and hilar tumors). Carcinomas involving the gall bladder are allowed.
2. Macroscopically complete resection within 8 weeks before start of chemotherapy.
3. Written informed consent.
4. Health status: WHO performance status (PS) 0-1
5. Age \>18 years
6. Adequate renal function (creatinine clearance ≥ 60 ml/min, calculated according to the formula of Cockcroft-Gault)
7. Adequate hepatic function (bilirubin ≤ 3 x LUN, AP ≤ 5 x LUN, ASAT ≤ 5 x LUN)
8. Adequate hematologic function: neutrophils ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l, Hb ≥ 9,5 mg/dl
9. Patient compliance and geographic proximity allowing proper staging, treatment and follow-up.
10. Women who are not breastfeeding and are using effective contraception if sexually active, who are not pregnant and agree not to become pregnant during participation in the trial or during the 12 months thereafter. A negative pregnancy test before inclusion into the trial is required for women \< 50 years. Men who agree not to father a child during participation in the trial or during the 12 months thereafter.

Exclusion criteria

1. Pregnancy or breastfeeding women
2. Previous malignancy within 5 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer
3. neutrophils \< 1.5 x 109/l, platelets \< 100 x 109/l, Hb \< 9,5 mg/dl
4. bilirubin \> 3 x LUN, ALAT \> 5 x LUN, ASAT \> 5 x LUN
5. Creatinine clearance \< 60 ml/min, calculated according to the formula of Cockcroft-Gault
6. Prior chemotherapy with gemcitabine
7. Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmias)
8. Psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
9. Active uncontrolled infection
10. Preexisting peripheral neuropathy (\> grade 1)
11. Serious underlying medical condition (judged by the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled diabetes mellitus, active autoimmune disease)
12. Concurrent treatment with other experimental drugs or other anti-cancer therapy; treatment in a clinical trial within 30 days prior to trial entry
13. Known hypersensitivity to the study drugs
B: Inclusion Criteria:

* Fully aware of the research and voluntarily signed informed consent (informed consent must be signed prior to the execution of any required test procedure);
* Patients received removal of biliary tract cancers that have been confirmed by histology or cytology, including intrahepatic bile duct carcinoma (IHCC), extrahepatic bile duct cancer (EHCC), and gallbladder cancer(GBC);
* Normal function of major organs that meets the following criteria:

Blood routine examination:

HB≥90 g/L； ANC≥1.5×109/L； PLT≥60×109/L；

Biochemical examination:

ALB ≥29 g/L； ALT and AST\<2.5ULN； TBIL ≤2ULN； Creatinine≤1.5ULN;

* ECOG physical condition scores 0 or 1;
* Fertile male or female patients volunteer to use effective contraception methods during the research period, such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine devices, etc.
* Fertile and non-lactational female who show negative in serum or urine pregnancy test within 7 days before inclusion for the study.

Exclusion Criteria:

* Those who received approved or on-going anti-tumor therapy within 4 weeks before the research;
* Those who received other anti-angiogenic tyrosine kinase inhibitors or monoclonal antibodies that had been approved or under study before the research;
* Abnormal laboratory tests that have significant clinical implication;
* International normalized ratio (INR) ≥ 1.5 or partially activated prothrombin time (APTT) ≥ 1.5 × ULN;
* The patient's current serum potassium, serum magnesium, or serum calcium is below the normal reference range of laboratory test (whether supplemented or not), or \>CTCAE grade 1;
* Patients currently suffering from hypertension that cannot be controlled with drugs;
* The researchers conclude electrolyte abnormalities that are clinically significant;
* There is severe bleeding or hemoptysis in the past or at current stage, or there are thromboembolic events within 12 months;
* Cardiovascular diseases that are clinically significant;
* ECG showed QTcB interval ≥ 480 milliseconds in resting state;
* Suffering from other malignant tumors in the past 5 years, excluding basal cell carcinoma or squamous cell carcinoma after receiving radical surgery, or carcinoma in situ of cervix;
* Active or uncontrollable serious infection (≥ CTCAE grade 2 infection), including but not limited to human immunodeficiency virus (HIV) infection;
* Known history of liver disease with evident significance;
* The patient currently has brain metastasis or spinal compression, except individual cases.
C: Inclusion Criteria:

* The patients with pathologic diagnosis of gallbladder carcinoma (GBCA) or extrahepatic cholangiocarcinoma (EHCC) after radical resection.
* The patients with pathologic stage T2-4 or N1 in R0 resection or positive resection margins (R1).
* Aged 18 to 70 years old, male or female, body condition score generally ECOG 0～2, expected survival ≥ 6 months.
* Subjects were no major organ dysfunction, blood, liver, kidney and heart function was normal, the specific requirements of laboratory indicators:

  * Blood: Absolute neutrophil count \> 1.5 × 109 / L, Platelet count \> 100 × 109 / L, Hb \> 8.0g/dl.
  * Liver function: serum bilirubin less than 1.5 times the upper limit of normal; ALT and AST less than 2.5 times the upper limit of normal.
  * Renal function: creatinine less than 1.5 times the upper limit of normal.
* Patients who can understand the circumstances of this study and signed informed consent.

Exclusion Criteria:

* Pregnancy, breast-feeding patients；
* Patients received prior anticancer therapy for the current malignancy or upper abdominal radiotherapy or chemotherapy at any time.
* Patients with malignant ascites.
* Patients with purulent and chronic infected wounds which delayed healing.
* Patients with liver, kidney and heart failure and coronary heart disease, angina, myocardial infarction, arrhythmia, cerebral thrombosis, stroke and other serious cardiovascular and cerebrovascular disease;
* Patients has a history of mental illness and difficult to control;
* Patients who was considered inappropriate to participate in the trials by the researchers.
D: All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility.

* Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded)
* Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy
* ECOG 0-1
* Age ≥18 years
* Adequate hematologic function
* Adequate liver function
* Adequate renal function
* No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy
* No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization
* Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women \<1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded)

Criteria for initial study enrolment

* Written informed consent
* No prior chemotherapy for cholangiocarcinoma
* No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer
* No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia)
* Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
* No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial
* Fertile women (\< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
* No pregnancy or lactation

Answer: A