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

NCT ID: NCT00777894

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2015-12-31

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.

Conditions

Liver Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiation: 3-dimensional conformal radiation therapy

Group Type: EXPERIMENTAL

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

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.

intensity-modulated radiation therapy

Intervention Type: RADIATION

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.

stereotactic body radiation therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Diana Naehrig, MD

Role: STUDY_CHAIR

Unviersitaetsspital Basel

Ilja Frank Ciernik, MD

Role: STUDY_CHAIR

Städtisches Klinikum Dessau

Daniel Aebersold, MD

Role: STUDY_CHAIR

Insel Gruppe AG, University Hospital Bern

Jean-Francois Dufour, MD

Role: STUDY_CHAIR

Insel Gruppe AG, University Hospital Bern

Locations

Maastro Lab at University of Maastricht

Maastricht, , Netherlands

Kantonsspital Aarau

Aarau, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Countries

Netherlands; Switzerland

References

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.

Reference Type: RESULT

PMID: 28086942 (View on PubMed)

Other Identifiers

SWS-SAKK-77/07

Identifier Type: -

Identifier Source: secondary_id

EU-20884

Identifier Type: -

Identifier Source: secondary_id

SWS-SASL-26

Identifier Type: -

Identifier Source: secondary_id

SAKK 77/07

Identifier Type: -

Identifier Source: org_study_id