Pilot study:Primary objective: feasibilitySecondary objectives: response rate, time to progression, overall survival and quality of life.Phase II study:Primary objective: efficacy.Secondary objectives: toxicity, especially grade 3 and 4 toxicities,…
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pilot study: toxicity
Phase II study: response rate.
Secondary outcome
Pilot study: response rate, time to progression, overall survival and quality
of life.
Phase II study: toxicity, especially grade 3 and 4 toxicities, time to
progression, overall survival and quality of life.
Background summary
Cholangiocarcinoma is a malignant gastrointestinal tumor of low incidence with
a poor prognosis. Chemotherapy is the most common treatment for advanced
disease. On the basis of a phase III clinical study, cisplatin plus gemcitabine
is considered standard first-line treatment in advanced cholangiocarcinoma
patients, but there is no established second-line therapy.
Since 5- fluorouracil (5-FU) and leucovorin combined with irinotecan and
oxaliplatin (FOLFIRINOX) appears to be safe and demonstrated efficacy in
clinical studies of advanced pancreatic cancer, colorectal cancer and
cholangiocarcinoma patients participating in a phase I study of solid tumors,
the combination could be an effective second-line treatment for patients with
advanced cholangiocarcinoma.
Study objective
Pilot study:
Primary objective: feasibility
Secondary objectives: response rate, time to progression, overall survival and
quality of life.
Phase II study:
Primary objective: efficacy.
Secondary objectives: toxicity, especially grade 3 and 4 toxicities, time to
progression, overall survival and quality of life.
Study design
Two steps design.
Step 1: pilot study, inclusion of 10 patients.
Step 2: phase II study, inclusion of 20 patients
Step 2 will be initiated if, :
1. at least 1 out of 10 patients in the pilot study show an objective response
and/or if at least 2 out of 10 patients show stable disease.
2. within the first 42 days (6 weeks) of treatment with FOLFIRINOX, maximal 3
patients out of 10 are admitted to the hospital as a result of treatment or if
maximal 3 patients out of 10 die or develop febrile neutropenia. Hospital
admission for treatment of biliary tract complications (e.g. biliary tract
obstruction) or death due to biliary tract complications will be not considered
in this futility analysis.
3. If more than 4 out of 10 patients require a dose reduction as a result of
toxicity within the first 42 days (6 weeks) and if there is enough response to
FOLFIRINOX treatment (as described above in item 1), the step 2 of this study
(phase II study) will be initiated with standard dose reduction (modified
FOLFIRINOX).
Intervention
Oxaliplatin 85 ml/m2, irinotecan 180 mg/m2 and leucovorin 400 mg/m2 every 2
weeks. Fluorouracil 400 mg/m2 followed by a continuous infusion of 2400 mg/m2
over a 46-hour period will be administrated at cycle 1. Beginning with cycle 2,
the 5-FU continuous-infusion dose will be adjusted based on 5-FU plasma
concentrations until the therapeutic range (AUC 20-25 mg.h.L-1) will be
reached.
Study burden and risks
The treatment applied has a high risk of side effects, but also a chance for
response. A wide variety of possible side effects are mentioned in the protocol
(page 27) and in the patient information sheet (page 8). Most side effects are
temporary and recover after cessation of treatment or dose reduction. For the
treatment, the patient will visit the hospital regularly. In order to avoid the
unnecessary exposure to this treatment, patients undergo regular evaluation
scans to assess the effect of the treatment. This allows a limitation of
unnecesarry exposure to the treatment and a limitation of possible sideeffects.
One of the drugs (5-FU) is given continuously during a 46 hours period,a
central venous access (eg, a PICC line or a port-a-cath) is standardly placed.
This is a small procedure with the advantage that patients do not have to stay
in hospital.
Also, there is already a lot of experience with this treatment in large groups
of patients (patients with pancreatic carcinoma), but there is little
experience with this treatment in the group of cholangio- and glablaascarcinoom
patients. Therefore, in a small group of patients (10) we will test the
feasibility of the treatment before this treatment will be given in a larger
group of patients (20 patients).
Meibergdreef 9
Amsterdam 1105AX
NL
Meibergdreef 9
Amsterdam 1105AX
NL
Listed location countries
Age
Inclusion criteria
- Histological or cytological diagnosis of cholangiocarcinoma. Histological
diagnosis is needed if a patient wants to participate in the translational
study (see section 11).
- Metastatic disease or unresectable locally advanced
cholangiocarcinoma.
- Measurable disease according RECIST criteria version 1.1.
- Age from 18 up to 75 year.
- ECOG performance status 0-1.
- Patients who received at least 3 cycles of gemcitabine/cisplatin in the
first-line.
- Adequate hematological function (WBC > 3.0 x 109/L, platelets > 100
x109/L)
- Adequate hepatic function (bilirubin * 1.5 x upper normal limit (ULN);
ALAT or ASAT <5x ULN in case of liver metastases and < 2.5 x ULN in
absence of liver metastases.
- Adequate renal function (creatinine clearance > 60 ml/min; creatinine
<120 µmol/L)
- Absence of cardiac insufficiency, chest pain (not medically controlled)
and myocardial infarction in the 12 months preceding study entry.
- Written informed consent.
Exclusion criteria
- Concurrent secondary malignancies or other malignancies within 3
years prior to enter this study with the exception of non-metastatic
basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
treated by cone-biopsy or resection
- Presence of cerebral or meningeal metastases
- Hypersensitivity to the active substance of oxaliplatin,
leucoverin,irinotecan and/ or 5-FU or to any of excipients used in these
drugs as described in Summary of Product Characteristics (SPCs).
- History of chronic diarrhea or colorectal inflammatory conditions
- Active infection or other serious underlying conditions which may
prevent the patient from receiving the planned treatment. For example:
prolonged unresolved bacterial cholangitis with destruction of bile duct
branches (e.g. after endoprothesis insertion) or two or more periods of
cholangitis in the last 6 months. Patients with other active or
uncontrolled severe infection, cirrhosis or chronic active hepatitis will be
excluded.
- Presence of cardiac insufficiency, unstable angina pectoris,
symptomatic congestive heart, failure myocardial infarction 6 months
prior to randomization, serious uncontrolled cardiac arrhythmia.
- Patients with peripheral sensory neuropathy with functional
impairment prior to the first cycle of FOLFIRINOX.
- Bone marrow depression after radiotherapy or treatment with other
antineoplastic drugs, defined as baseline values neutrophils <2 x 109 / L
and / or platelets <100 x 109 / L.
- Current iInclusion in another investigational clinical trial of cancer
treatment.
- Patients who use Azole antifungals and/or anti-cancer medication at
inclusion (see section 6.1.6). Patients who use brivudine, sorivudine and
there analogs. Patiënt with concomitant use of St. John's wort
preparations.
- Pernicious anemia or other anaemias due to vitamin B 12 deficiency.
- Males who wish to have children while receiving this chemotherapy or
within 6 months after the end of participation in this study.
- Women who are pregnant, breast-feeding or not using adequate
contraceptive
- Age younger than 18 or older than 75 years
- ECOG performance status >1.
- Incapacitated persons who are not able to provide consent.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTRNL2015-001378--NL |
| ClinicalTrials.gov | NCT02456714 |
| CCMO | NL53822.018.15 |