Trial objectivesThe objective of the phase I is to assess the feasibility and safety of radiotherapy (RT) in hepatocellularcarcinoma (HCC).The objective of the phase II is to assess the efficacy and safety of RT in HCC.Additional research…
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
Primary endpoint of phase I
• Dose limiting toxicity (DLT) of RT
Primary endpoint of phase II
• Best objective response of target liver lesions according to RECIST
Secondary outcome
Secondary endpoints of phase I
• Best objective response of target liver lesions according to RECIST
• Adverse events (AEs)
Secondary endpoints of phase II
• Volumetric response of target liver lesions at 5 months
• Time to progression of target liver lesions
• Duration of response of target liver lesions
• Stable disease of target liver lesions
• Time to liver event
• Progression-free survival (PFS)
• Overall survival (OS)
• Compensatory liver tissue hypertrophy
• Child-Pugh Score
• Adverse events (AEs)
• Serum alpha fetoprotein (AFP) level
Background summary
RATIONALE
HCC is the fifth most common cancer worldwide with increasing incidence rates
in Europe and high mortality
rates. The symptoms, disease progression and thus prognosis are primarily
defined by the size and localization
of the tumor and accessibility to therapy. The standard care for non-resectable
liver cancer is TACE. Alternative
methods are radiofrequency ablation (RFA), nuclear therapy with intra-arterial
radioactive beads and ionizing
radiation. Ionizing radiation is a highly effective single agent against HCC.
Radiotherapy has been underused in
the past due to technical inadequacy. More recent technical developments such
as image-guided radiotherapy,
CT-based RT planning, and 3D-conformal dose delivery allow minimizing the dose
to non-target tissue such as
non-affected liver tissue, kidneys and the gut. Thus, less collateral dose
delivery to healthy neighboring tissue
allows dose escalation to the diseased segments. The present trial is the first
to investigate and define the
potential role of high dose external beam RT for non-resectable HCC in
Switzerland and a few centers abroad,
seeking to establish RT as a potential experimental arm in a subsequent phase
III trial.
Study objective
Trial objectives
The objective of the phase I is to assess the feasibility and safety of
radiotherapy (RT) in hepatocellular
carcinoma (HCC).
The objective of the phase II is to assess the efficacy and safety of RT in HCC.
Additional research question
The subproject of the phase II of this trial is a proteomics analysis of blood
serum samples taken before and
after RT. The objectives are the generation of reproducible peptide patterns,
assessment of changes in the
proteome and the detection of peptides that discriminate between the situation
before and after RT.
Study design
Phase I:
- dose escalation of radiotherapy (RT)
- 5 levels (level 1/2/3: 3 patients, level 4/5: 5 patients)
- determination of the maximum tolerated dose (MTD)
Phase II:
- radiotherapy at MTD-level (if >= 62 Gy)
- sample size: 43 evaluable patients
- assessment of efficacy and safety
Intervention
Once daily RT sessions with 2 Gy, five days a week (on weekdays), will be
performed.
Phase I: Dose finding according to the following escalation table:
Dose level Radiotherapy dose (1 x 2 Gy session/day, 5 sessions/week)
1 (3 patients) 27 x 2 Gy = 54 Gy
2 (3 patients) 29 x 2 Gy = 58 Gy, with optional field reduction after a dose of
54 Gy
3 (3 patients) 31 x 2 Gy = 62 Gy, with optional field reduction after a dose of
54 Gy
4 (5 patients) 33 x 2 Gy = 66 Gy, with optional field reduction after a dose of
54 Gy
5 (5 patients) 35 x 2 Gy = 70 Gy, with optional field reduction after a dose of
54 Gy
Phase II: The dose for phase II will be recommended according to the MTD
determined in phase I, if the MTD is
62 Gy or higher. If the MTD is 58 Gy or lower, the phase II part of the trial
will not be performed.
Study burden and risks
Phase
during RT:
- daily (5/week) RT for 6-7 week, depending on the dosis level (27, 29, 31, 33
or 35 sessions)
- weekly physical examination and bloodexamination
During FU (11 months)
- 1 m after RT: bloodexaminiation
- 1, 2, 3, 5, 8 en 11 m after RT physical examination
- CT or MRI liver 2, 5, 8 en 11 m after RT or until progression
fase II
during RT:
- daily (5/week) RT during 6- 7 weeks, dosis depending on the results of fase
I
- weekly physical examination and bloodexamination
during FU (35 months)
- 1 m after RT: bloodexamination
- 1, 2, 3, 5, 8, 11, 15, 19, 23, 29 and 35 months after RT physical examination
- CT or MRI liver 2, 5, 8, 11 , 15, 19, 23, 29 and 35 months after RT or until
progression
Effingerstrasse 40
Bern CH-3008
CH
Effingerstrasse 40
Bern CH-3008
CH
Listed location countries
Age
Inclusion criteria
1.patient must give informed consent before registration
2.confirmed diagnosis of HCC
3.stage: cT2-4, cN0-1, M0 or unresectable cT1,cN0-1,M0
4.cirrhosis Child-Pugh class A or B
5.measurable disease
6.residual liver volume: >= 800 ml or >= 40% of total liver volume
7.WHO 0-2
8.adequate hematological volumes
9.adequate hepatic functions
10.adequate coagulation parameter
11.adequate renal function
12.age >= 18
13.ability to tolerate proton-pump inhibitors or H2 antagonists during RT
14.women:not pregnant and adequate contraception must be used; men: agree not to father a child during/ within 4 months after trial
15. compliance and geographic proximity to allow proper staging and follow-up
16. phase I only:adequate pancreatic function
Exclusion criteria
1.previous malignancy within 5 years
2.previous RT to the abdomen or caudal chest
3.TACE, RFA or RT within 8 weeks before registration
4. concurrent treatment with other experimental drugs or other anti-cancer therapy
5.operable disease (curative intent) or planned liver transplantation
6.nutritional intake < 1500 kcal/day
7.weight loss > 15%
8.presence of clinical ascites
9.presence of encephalopathy
10.recent myocard infarction
11.esophageal varices >or = gr 3
12.syptoms of colitis, enteritis, esophagitis, fistula, gastristis, ileus, necrosis, perforation, stricture or ulcer
13.severe anorexia, constipation, dehydration, diarrhea or vomiting
14.any serious underlyuing condition which could impair teh ability of the patient to participate in the trial
15.concommitant treatment with steroids or NSAIDs durinng RT
16.psychiatric disorder precluding understanding of information on trial related topics or giving informed consent
Design
Recruitment
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 |
|---|---|
| Other | NCT00777894 |
| CCMO | NL25647.068.08 |