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

NCT00777894 | Completed Phase 1

• 4 other identifiers: SAKK 77/07SWS-SAKK-77/07EU-20884SWS-SASL-26
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 6

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.

Conditions

Liver Cancer

Keywords

advanced adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (Phase I)

  during RT or within 30 days after the last RT dose, is a DLT.

• Best objective response of target liver lesions (TLLs)

  according to RECIST criteria for up to 1 year after completion of study therapy (Phase II)

Secondary Outcomes (12)

• Best objective response of TLLs according to RECIST criteria (Phase I)

  according to RECIST criteria (Phase I)

• Adverse events according to NCI CTCAE v.3.0

  during therapy and within 3 months after completion of study therapy (Phases I and II)

• Volumetric response of TLLs

  at 5 months after completion of study therapy (Phase II)

• Time to progression of TLLs (Phase II)

  calculated from registration until documented tumor progression of target liver lesions.

• Duration of response of TLLs (Phase II)

  the time from achieving an objective response (CR + PR) to a progression of target liver lesions according to RECIST or death.

Study Arms (1)

Radiation: 3-dimensional conformal radiation therapy

EXPERIMENTAL

Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy; Radiation: stereotactic body radiation therapy

Interventions

3-dimensional conformal radiation therapy 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.

Radiation: 3-dimensional conformal radiation therapy

intensity-modulated radiation therapy 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.

Radiation: 3-dimensional conformal radiation therapy

stereotactic body radiation therapy 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.

Radiation: 3-dimensional conformal radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (6)

Maastro Lab at University of Maastricht

Maastricht, 6200MD, Netherlands

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, CH-6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 28086942 RESULT

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Diana Naehrig, MD

  Unviersitaetsspital Basel

  STUDY CHAIR

• Ilja Frank Ciernik, MD

  Städtisches Klinikum Dessau

  STUDY CHAIR

• Daniel Aebersold, MD

  Insel Gruppe AG, University Hospital Bern

  STUDY CHAIR

• Jean-Francois Dufour, MD

  Insel Gruppe AG, University Hospital Bern

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 22, 2008
• Study Start: November 1, 2008
• Primary Completion: January 1, 2014
• Study Completion: December 1, 2015
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (5); NL (1)