Patient case: 64-year-old male with Cholangiocarcinoma. Genetic variant: IDH1 (R132H). Other conditions: Neuropathy.

Clinical trial: Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Observation After Curative Intent Resection of Biliary Tract Cancer

Summary: This is a multicentre, prospective, randomized, controlled phase III trial designed to assess the clinical performance of gemcitabine with cisplatin and observation vs. observation alone in patients after curative intent resection of cholangiocarcinoma and muscle invasive gall bladder carcinoma.

Detailed description: The ACTICCA-1 investigator initiated trial is funded by the Deutsche Krebshilfe (grant number 110215) and supported my medac. With respect to data obtained in the ABC-02 trial, the combination of cisplatin and gemcitabine for 24 weeks as investigational treatment was selected. Based on adjuvant trials in pancreatic cancer (e.g. ESPAC IV) with a comparable postoperative recovery time, inclusion of patients within a maximum interval of 16 weeks between surgery and start of CTx was chosen. Due to the different prognosis and treatment susceptibility of muscle invasive carcinoma, two separate cohorts for CCA and GBCA were included to capture the expected treatment effects. Randomization will be stratified for lymph node status for both cohorts and localization for CCA. The primary endpoint is DFS and secondary endpoints include OS, safety and tolerability of adjuvant CTx, quality of life, and patterns of disease recurrence. In both cohorts, randomization will be 1:1 with adjuvant CTx for 24 weeks and imaging every 12 weeks in the experimental arm and observation only in the control arm.

Eligibility: 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

Relevance to patient case: not relevant