Radiation Therapy in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00777894
First received: October 21, 2008
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Radiation: stereotactic body radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: External Beam Radiotherapy for Unresectable Hepatocellular Carcinoma. A Multicenter Phase I/II Trial.

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Dose-limiting toxicity (Phase I) [ Time Frame: during RT or within 30 days after the last RT dose, is a DLT. ] [ Designated as safety issue: Yes ]
  • Best objective response of target liver lesions (TLLs) [ Time Frame: according to RECIST criteria for up to 1 year after completion of study therapy (Phase II) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Best objective response of TLLs according to RECIST criteria (Phase I) [ Time Frame: according to RECIST criteria (Phase I) ] [ Designated as safety issue: No ]
  • Adverse events according to NCI CTCAE v.3.0 [ Time Frame: during therapy and within 3 months after completion of study therapy (Phases I and II) ] [ Designated as safety issue: Yes ]
  • Volumetric response of TLLs [ Time Frame: at 5 months after completion of study therapy (Phase II) ] [ Designated as safety issue: No ]
  • Time to progression of TLLs (Phase II) [ Time Frame: calculated from registration until documented tumor progression of target liver lesions. ] [ Designated as safety issue: No ]
  • Duration of response of TLLs (Phase II) [ Time Frame: the time from achieving an objective response (CR + PR) to a progression of target liver lesions according to RECIST or death. ] [ Designated as safety issue: No ]
  • Stable disease of TLLs (Phase II) [ Time Frame: will be determined according to RECIST ] [ Designated as safety issue: No ]
  • Time to liver event (Phase II) [ Time Frame: from registration until progressive liver disease. ] [ Designated as safety issue: No ]
  • Progression-free survival (Phase II) [ Time Frame: calculated from registration until documented tumor progression or death, whichever occurs first. ] [ Designated as safety issue: No ]
  • Overall survival (Phase II) [ Time Frame: calculated from registration until death ] [ Designated as safety issue: No ]
  • Compensatory liver tissue hypertrophy at baseline and at 5 months after completion of study therapy (Phase II) [ Time Frame: Increase in residual liver volume (= total liver - GTV) (ml) between registration and 5 months after RT will be calculated ] [ Designated as safety issue: No ]
  • Child-Pugh Score [ Time Frame: at last study visit and at 1, 2, 3, and 5 months after completion of study therapy (Phase II) ] [ Designated as safety issue: No ]
  • Serum alpha-fetoprotein level (Phase II) [ Time Frame: will be measured until progression, if AFP is ≥ 1.5 x ULN at baseline. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 73
Study Start Date: November 2008
Estimated Study Completion Date: December 2016
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radiation: 3-dimensional conformal radiation therapy Radiation: 3-dimensional conformal radiation therapy

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.

Radiation: intensity-modulated radiation therapy

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.

Radiation: stereotactic body radiation therapy

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.


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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00777894

Locations
Netherlands
Maastro Lab at University of Maastricht
Maastricht, Netherlands, 6200MD
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland, CH-6500
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Diana Naehrig, MD Unviersitaetsspital Basel
Study Chair: Ilja Frank Ciernik, MD Städtisches Klinikum Dessau
Study Chair: Daniel Aebersold, MD University Hospital Inselspital, Berne
Study Chair: Jean-Francois Dufour, MD University Hospital Inselspital, Berne
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00777894     History of Changes
Other Study ID Numbers: SAKK 77/07, SWS-SAKK-77/07, EU-20884, SWS-SASL-26
Study First Received: October 21, 2008
Last Updated: January 16, 2014
Health Authority: Switzerland: Ethikkommission

Keywords provided by Swiss Group for Clinical Cancer Research:
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
adult primary hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 23, 2014