Adjuvant chemotherapy with gemcitabine and cisplatin compared to standard of care after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial)
Efficacy and safety of adjuvant chemotherapy with gemcitabine and cisplatin compared to capecitabine after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1)
Australasian Gastro-Intestinal Trials Group
40 participants
Jan 24, 2017
Interventional
Conditions
Summary
The purpose of this study is to determine whether or not treating patients with cisplatin and gemcitabine chemotherapy helps reduce the risk of cancer returning. Who is it for? ACTICCA-1 is a clinical research study for people who have a cancer of the biliary tract (cancer of the gall bladder or bile duct, also known as cholangiocarcinoma in medical terms) which has been removed in an operation. Study details These drugs are being tested as they have been shown to be the most effective chemotherapy combination in more advanced cases of biliary tract cancer, where the disease is inoperable or has spread to other areas of the body. This is an international investigator initiated study called ACTICCA-1, which is being led by the University Medical Centre Hamburg- Eppendorf in Germany and conducted in Australia by the Australasian Gastro-Intestinal Trials Group (AGITG) in collaboration with the National Health and Medical Research Centre Clinical Trials Centre (NHMRC CTC), University of Sydney. The study involves randomly allocating participants to receive either chemotherapy with cisplatin and gemcitabine or the current standard of care (capecitabine). The drugs used in this study are approved in Australia to treat various cancers, however they do not have a specific listing by the Australian Therapeutics Goods Administration (TGA) for biliary tract cancer It is hoped that the findings of this study will provide details on whether giving cisplatin and gemcitabine chemotherapy following surgery for cancer of the biliary tract is a safe and effective treatment to reduce the chance of disease progression and increase survival time and quality of life. Radiotherapy Sub-Study – Second Randomisation for R1 Patients at Participating Sites The purpose of the radiotherapy sub-study is to assess the role of adding radiation to chemotherapy in a subgroup of participants to see whether the addition of radiation can further reduce the risk of relapse. Only participants with R1 resections (cancer cells present microscopically at the resection margin) to will be asked to join the sub-study. Participants will be assigned into groups for a second time to either continue to complete their chemotherapy course or to receive chemoradiation (radiation therapy and capecitabine) for a period of 5 weeks, after the initial 18 weeks of chemotherapy (arms AR and BR, described below). Patients are followed up for 5 years maximum from randomisation.
Eligibility
Inclusion Criteria39
- Eligibility criteria for treatment phase:
- Histologically confirmed non-metastatic 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) (according to
- appendix H)
- Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled
- start of chemotherapy
- ECOG 0-1
- Age greater than or equal to 18 years
- Adequate hematologic function: ANC larger than or equal to 1.5 x 10^9/L, platelets larger than or equal to 100 x10^9/L, hemoglobin larger than or equal to 9 g/dl or larger than or equal to 5.59 mmol/L
- Adequate liver function as measured by serum transaminases (AST and ALT) less than or equal to 5 x ULN and bilirubin less than or equal to 3 x ULN
- Adequate renal function, i.e. serum creatinine less than or equal to 1.5 x ULN, glomerular filtration rate greater than or equal to 50 ml/min (determination of GFR according to local institutional standards, e.g. MDRD, (Appendix E))
- 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 less than 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 biliary tract cancer
- No previous malignancy within 3 years or concomitant malignancy, except those
- with a 5 year overall survival rate of more than 90%, e.g. 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
- Additional eligibility criteria for patients to be included in the radiotherapy substudy:
- R1 (microscopic positive margin)
- No previous radiotherapy to abdomen
Exclusion Criteria7
- Prior chemotherapy for biliary tract cancer
- Previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90% e.g non-melanomatous skin cancer or adequately treated in-situ cervical cancer
- 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
- Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
- Serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial
- Fertile women (less than 1 year after last menstruation) and procreative men unwilling and unable to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
- Pregnancy or lactation
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Interventions
All patients eligible for the treatment phase in stage 2 will be randomized to adjuvant chemotherapy with gemcitabine and cisplatin and observation or capecitabine and observation, followed by an immediate second randomization for patients meeting the specific radiotherapy sub-study selection criteria (R1 resection, no prior abdominal radiotherapy) and consenting in participation in the substudy. Arm A: Gemcitabine/cisplatin and observation Therapy will be administered on days 1 and 8 every 3 weeks for 24 weeks (8 cycles), with cisplatin (25 mg per square meter of body surface area) and gemcitabine (1000 mg per square meter) (Valle, Wasan et al. 2010). Arm B: Capecitabine and observation Therapy will be administered from day 1 to 14 every 3 weeks for 24 weeks (8 cycles), with capecitabine 2500 mg per square meter of body surface area per day (1250 mg per square meter of body-surface area, twice daily). In addition, eligible patients with R1 resection included in sites participating in the radiotherapy sub-study will be randomized between 24 weeks chemotherapy (gemcitabine/cisplatin or capecitabine) or 18 weeks of chemotherapy (gemcitabine/cisplatin or capecitabine) followed by chemoradiation with capecitabine. Arm AR: Gemcitabine/cisplatin followed by chemoradiation and observation Therapy will be administered on days 1 and 8 every 3 weeks for 18 weeks (6 cycles), with cisplatin (25 mg per square meter of body surface area) and gemcitabine (1000 mg per square meter) (Valle, Wasan et al. 2010), followed by chemoradiation with a total dose of 45Gy to elective nodal area and 55Gy to R1 delivered as a simultaneous integrated boost in 25 daily fractions over 5 weeks with concomitant capecitabine at 1330 mg per square meter of body-surface area per day (665 mg per square meter, twice daily) on radiotherapy days (5 days per week). Arm BR: Capecitabine followed by chemoradiation and observation Therapy will be administered from day 1 to 14 every 3 weeks for 18 weeks (6 cycles), with capecitabine 2500 mg per square meter of body surface area per day (1250 mg per square meter, twice daily) followed by chemoradiation with a total dose of 45Gy to elective nodal area and 55Gy to R1 delivered as a simultaneous integrated boost in 25 daily fractions over 5 weeks with concomitant capecitabine at 1330 mg per square meter of body-surface area per day (665 mg per square meter, twice daily) on radiotherapy days (5 days per week). Radiotherapy Radiotherapy should start not more than 6 weeks after day 1 of cycle 6. A contrast enhanced liver protocol CT must be obtained for treatment planning in custom immobilisation. A linear accelerator with at least 6 MV should be used, capable of daily image guidance and IMRT delivery. Radiation therapy will be given daily, five times weekly. Online imaging prior to each fraction of radiotherapy is mandatory.
Locations(16)
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ACTRN12615001283561