Clinical trial NCT00777894: Radiation Therapy in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Official title: External Beam Radiotherapy for Unresectable Hepatocellular Carcinoma. A Multicenter Phase I/II Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Liver Cancer
Keywords: advanced adult primary liver cancer
localized unresectable adult primary liver cancer
adult primary hepatocellular carcinoma
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2008-10-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. This may be an effective treatment for liver cancer.

PURPOSE: This phase I/II trial is studying the side effects and best dose of external-beam radiation therapy in treating patients with liver cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

* To assess the feasibility and safety of radiotherapy (RT) in patients with hepatocellular carcinoma. (Phase I)
* To assess the safety and efficacy of RT in these patients. (Phase II)
* To generate reproducible peptide patterns of the serum proteome or specific serum sub proteomes in these patients.
* To assess changes in the proteome or sub proteome patterns after RT in these patients.
* To detect peptides that discriminate between before and after RT in these patients.
* To identify these discriminating peptides in these patients.

OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.

Patients undergo radiotherapy (RT) once daily, five days a week, for 6 weeks. Intensity-modulated, 3-dimensional conformal, or fractionated stereotactic RT may be used.

After completion of study therapy, patients in the phase I portion are followed for 1 year and patients in the phase II portion are followed for 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically, cytologically, or radiologically confirmed hepatocellular carcinoma

  * Clinical stage T2-4, N0-1, M0 (stage II, IIIA, IIIB, IIIC) OR unresectable T1, N0-1, M0 (stage I) disease

    * M1 disease allowed in phase I if at least 90% of the tumor load (volume) is in the liver
* Measurable disease (at least one liver lesion that can be measured in at least one dimension as ≥ 10 mm in multislice CT scan/MRI)
* Volumetry of liver tumor and residual liver tissue: residual liver volume (= total liver volume - gross tumor volume) has to be ≥ 800 mL and ≥ 40% of total liver volume
* No operable disease (with curative intent or planned liver transplantation)
* No presence of clinical ascites

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* Cirrhosis Child-Pugh class A or B (Child-Pugh score of ≤ 9)
* Hemoglobin ≥ 100 g/L
* ANC ≥ 1,200/mm³
* Platelet count ≥ 50,000/mm³
* ALT and AST ≤ 7 times upper limit of normal (ULN)
* AP ≤ 10 times ULN
* Bilirubin ≤ 50 μmol/L
* INR ≤ 2
* Creatinine clearance ≥ 50 mL/min
* Functional left kidney (scintigraphy mandatory for phase I, phase II only if indicated)
* Lipase ≤ 2 times ULN (phase I only)
* Able to tolerate proton-pump inhibitors or H2 antagonists during radiation therapy
* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 4 months after completion of study therapy
* No prior malignancy allowed, except for the following:

  * Adequately treated cervical carcinoma in situ
  * Adequately treated localized nonmelanoma skin cancer
  * Any other malignancy from which patient has been disease-free for 5 years
* No presence of medically uncontrolled encephalopathy
* No myocardial infarction within the past 6 months
* No esophageal varices ≥ grade 3, with red signs, or bleeding within the past 3 months
* No symptoms of colitis, enteritis, esophagitis, fistula, gastritis, ileus, necrosis, perforation, stricture, or ulcer
* No severe anorexia, constipation, dehydration, diarrhea, or vomiting
* No serious underlying medical condition that, in the opinion in the investigator, would preclude study participation (e.g., active autoimmune disease or uncontrolled diabetes)

  * Portal vein thrombosis allowed
* No psychiatric disorder precluding understanding of information on study related topics or giving informed consent
* No nutritional intake \< 1500 calories per day (corrected)
* No weight loss ≥ 15 % within the past 3 months

PRIOR CONCURRENT THERAPY:

* At least 8 weeks since prior transarterial chemoembolization (TACE), radiofrequency ablation, or radiotherapy (RT) unless progressive disease was documented after this therapy
* At least 21 days since prior and no other concurrent treatment with experimental drugs
* At least 21 days since prior and no other concurrent treatment on another clinical trial
* At least 21 days since prior and no other concurrent anticancer therapy
* No prior RT to the abdomen or caudal chest

  * Prior RT to pelvis allowed
  * Prior RT to chest must be above D5 vertebra
  * Portal vein embolization ligation or pre-RT TACE allowed
* No concurrent treatment with steroids or non-steroidal anti-inflammatory drugs during RT (proton-pump inhibitor allowed)

Primary outcomes:
measure: Dose-limiting toxicity (Phase I)
timeFrame: during RT or within 30 days after the last RT dose, is a DLT.
measure: Best objective response of target liver lesions (TLLs)
timeFrame: according to RECIST criteria for up to 1 year after completion of study therapy (Phase II)
Secondary outcomes:
measure: Best objective response of TLLs according to RECIST criteria (Phase I)
timeFrame: according to RECIST criteria (Phase I)
measure: Adverse events according to NCI CTCAE v.3.0
timeFrame: during therapy and within 3 months after completion of study therapy (Phases I and II)
measure: Volumetric response of TLLs
timeFrame: at 5 months after completion of study therapy (Phase II)
measure: Time to progression of TLLs (Phase II)
timeFrame: calculated from registration until documented tumor progression of target liver lesions.
measure: Duration of response of TLLs (Phase II)
timeFrame: the time from achieving an objective response (CR + PR) to a progression of target liver lesions according to RECIST or death.
measure: Stable disease of TLLs (Phase II)
timeFrame: will be determined according to RECIST
measure: Time to liver event (Phase II)
timeFrame: from registration until progressive liver disease.
measure: Progression-free survival (Phase II)
timeFrame: calculated from registration until documented tumor progression or death, whichever occurs first.
measure: Overall survival (Phase II)
timeFrame: calculated from registration until death
measure: Compensatory liver tissue hypertrophy at baseline and at 5 months after completion of study therapy (Phase II)
timeFrame: Increase in residual liver volume (= total liver - GTV) (ml) between registration and 5 months after RT will be calculated
measure: Child-Pugh Score
timeFrame: at last study visit and at 1, 2, 3, and 5 months after completion of study therapy (Phase II)
measure: Serum alpha-fetoprotein level (Phase II)
timeFrame: will be measured until progression, if AFP is ≥ 1.5 x ULN at baseline.
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastro Lab at University of Maastricht
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital Bern
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
Study officials:
affiliation: Unviersitaetsspital Basel
name: Diana Naehrig, MD
role: STUDY_CHAIR
affiliation: Städtisches Klinikum Dessau
name: Ilja Frank Ciernik, MD
role: STUDY_CHAIR
affiliation: Insel Gruppe AG, University Hospital Bern
name: Daniel Aebersold, MD
role: STUDY_CHAIR
affiliation: Insel Gruppe AG, University Hospital Bern
name: Jean-Francois Dufour, MD
role: STUDY_CHAIR
References:
citation: Herrmann E, Naehrig D, Sassowsky M, Bigler M, Buijsen J, Ciernik I, Zwahlen D, Pellanda AF, Meister A, Brauchli P, Berardi S, Kuettel E, Dufour JF, Aebersold DM; Swiss Group for Clinical Cancer Research (SAKK). External beam radiotherapy for unresectable hepatocellular carcinoma, an international multicenter phase I trial, SAKK 77/07 and SASL 26. Radiat Oncol. 2017 Jan 13;12(1):12. doi: 10.1186/s13014-016-0745-0.