This study has been transitioned to CTIS with ID 2024-517340-61-00 check the CTIS register for the current data. The primary objective of this study is to evaluate the efficacy of gemcitabine and cisplatin compared with standard of care (adjuvant…
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Disease free survival (DFS)
Secondary outcome
- Disease free survival rate at 24 months
- Recurrence free survival
- Overall survival (OS)
- Safety and tolerability of adjuvant chemotherapy
- Quality of life (QoL)
- Function of biliodigestive anastomosis
- Rate and severity of biliary tract infections
- Patterns of disease recurrence
- Locoregional control
Background summary
Survival after curative intent surgery in BTC is poor due to high rates of
disease recurrence. Data from clinical trials and retrospective analyses
suggest a benefit of the use of adjuvant treatment with either chemotherapy or
chemoradiation. The most recent results of the BILCAP trial in 447 patients
showed a significantly improved RFS in favor of capecitabine (17.6 months vs.
24.6 months, HR 0.76, 95% CI: 0.58-0.99, p=0.039). Furthermore, the primary
endpoint (OS) was clinically relevant, although non-significantly improved from
36.4 months to 51.1 months in the intent to treat population (HR 0.81, 95% CI:
0.63-1.04, p=0.097) (Primrose, Fox et al. 2017).
With respect to current datga obtained in a large randomized phase III trial
(Valle, Wasan et al. 2010), the combination of cisplatin and gemcitabine for 24
weeks was chosen for this clinical trial to compare with the new standard
adjuvant therapy capecitabine.
Study objective
This study has been transitioned to CTIS with ID 2024-517340-61-00 check the CTIS register for the current data.
The primary objective of this study is to evaluate the efficacy of gemcitabine
and cisplatin compared with standard of care (adjuvant capecitabine) in
patients with BTC after complete resection in terms of DFS.
Secondary objectives are safety and tolerability of the treatment as well as
OS, quality of life, function of biliodigestive anastomoses, and evaluation of
the quantity and quality of information patients have gained after the informed
consent as well as of the involvement
of patients in the decision-making process (shared decision making).
Study design
This is a multicentre, prospective, randomized, controlled phase III trial
designed to assess the clinical performance of gemcitabine with cisplatin vs.
standard of care (adjuvant capecitabine) in patients after curative intent
resection of BTC.
Intervention
Arm A Gemcitabine (1000 mg/m2 iv) + cisplatin (25 mg/m2 iv) every 3 weeks on
day 1 and 8 for 24 weeks followed by observation
Arm B capecitabine (1250mg/m2 oral) day1-14 every 3 weeks
Arm A&B followed every 3 months via CT or MRI for two years followed by 6
monthly abdominal ultrasound for further 3 years, together with clinical
evaluation, and determination of CA 19-9.
Study burden and risks
Side effects occur as a result of treatment:
the most frequent side effects of Gemcitabine are: bone marrow suppression,
respiratory insufficiency, vomiting, nausea, rash, alopecia, hematuria, hepatic
dysfunction, flu-like symptoms and edema.
The most frequent side effects of cisplatin are: bone marrow suppression,
increased risk of infection, hearing loss, anorexia, nausea, vomiting and
diarrhea. Renal impairment and fever.
de Boelelaan 1117
Amsterdam 1081HV
NL
de Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Eligibility criteria for enrolment phase
1. Suspicion of or histologically/cytologically confirmed adenocarcinoma of
biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle
invasive gallbladder carcinoma) scheduled for radical surgical therapy
2. Written informed consent
3. No prior chemotherapy for biliary tract cancer
4. No previous malignancy within 3 years or concomitant malignancy, except:
nonmelanomatous
skin cancer or adequately treated in situ cervical cancer
5. 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)
6. Absence of psychiatric disorder precluding understanding of information of
trial
related topics and giving informed consent
7. No serious underlying medical conditions (judged by the investigator), that
could impair the ability of the patient to participate in the trial
8. 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)
9. No pregnancy or lactation
Eligibility criteria for treatment phase (before randomization)
1. 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)
2. Macroscopically complete resection (R0/1) within 6 (-16) weeks before
scheduled
start of chemotherapy
3. ECOG 0-1
4. Age >18 years
5. Adequate hematologic function: ANC >= 1.5 x 109/L, platelets >= 100
x109/L,hemoglobin >= 9 g/dl or >= 5.59 mmol/L
6. Adequate liver function as measured by serum transaminases (AST and ALT) <=5 x
ULN and bilirubin <=3 x ULN
7. Adequate renal function, i.e. serum creatinine <= 1.5 x ULN, glomerular
filtration rate
>= 60 mL/min (MDRD)
8. No active uncontrolled infection, except chronic viral hepatitis under
antiviral therapy
9. No concurrent treatment with other experimental drugs or other anti-cancer
therapy, treatment in a clinical trial within 30 days prior to randomization
10. Negative serum pregnancy test within 7 days of starting study treatment in
premenopausal
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)
Exclusion criteria
n.a.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-517340-61-00 |
| EudraCT | EUCTR2012-005078-70-NL |
| ClinicalTrials.gov | NCT02170090 |
| CCMO | NL46428.018.14 |