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Liver CancerPhase 1/2NCT00777894

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

A Phase 1/2 study testing 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy and stereotactic body radiation therapy in people with Liver Cancer, run by Swiss Cancer Institute at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Cancer
What is being tested?
3-dimensional conformal radiation therapy, intensity-modulated radiation therapy and stereotactic body radiation therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
6 sitesin 2 countries
Study dates
Nov 2008to Dec 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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)

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Switzerland5 sites

  • Kantonsspital Aarau

    Aarau, CH-5001

  • Universitaetsspital-Basel

    Basel, CH-4031

  • Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

    Bellinzona, CH-6500

  • Inselspital Bern

    Bern, CH-3010

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

Other trials in Switzerland

Netherlands1 site

  • Maastro Lab at University of Maastricht

    Maastricht, 6200MD

Other trials in Netherlands

About this study

Official title: External Beam Radiotherapy for Unresectable Hepatocellular Carcinoma. A Multicenter Phase I/II Trial.

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.

Read the 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
Being tested
3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy
Keywords
advanced adult primary liver cancer, localized unresectable adult primary liver cancer, adult primary hepatocellular carcinoma
Medical subject headings
Liver Neoplasms, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 3-dimensional conformal radiation therapyRadiation

    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 therapyRadiation

    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 therapyRadiation

    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 groups in NCT00777894
Study groupRoleWhat they receive
Radiation: 3-dimensional conformal radiation therapyExperimentalNot described
Receives: Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy; Radiation: stereotactic body radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (Phase I)

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

  2. Best objective response of target liver lesions (TLLs)

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

Secondary outcomes (12)

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

    Measured: according to RECIST criteria (Phase I)

  2. Adverse events according to NCI CTCAE v.3.0

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

  3. Volumetric response of TLLs

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

  4. Time to progression of TLLs (Phase II)

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

  5. Duration of response of TLLs (Phase II)

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

  6. Stable disease of TLLs (Phase II)

    Measured: will be determined according to RECIST

  7. Time to liver event (Phase II)

    Measured: from registration until progressive liver disease.

  8. Progression-free survival (Phase II)

    Measured: calculated from registration until documented tumor progression or death, whichever occurs first.

  9. Overall survival (Phase II)

    Measured: calculated from registration until death

  10. Compensatory liver tissue hypertrophy at baseline and at 5 months after completion of study therapy (Phase II)

    Measured: Increase in residual liver volume (= total liver - GTV) (ml) between registration and 5 months after RT will be calculated

  11. Child-Pugh Score

    Measured: at last study visit and at 1, 2, 3, and 5 months after completion of study therapy (Phase II)

  12. Serum alpha-fetoprotein level (Phase II)

    Measured: will be measured until progression, if AFP is ≥ 1.5 x ULN at baseline.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2008 (estimated)
  2. Study startNov 2008
  3. Primary completionJan 2014
  4. Study completionDec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00777894
Sponsor's protocol ID
SAKK 77/07
Other IDs
SWS-SAKK-77/07, EU-20884, SWS-SASL-26
Status last verified
May 2019
First submitted
21 Oct 2008
Last updated
15 May 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 28086942

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy and stereotactic body radiation therapy in people with Liver Cancer, run by Swiss Cancer Institute at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Switzerland, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (Phase I) (time frame: during RT or within 30 days after the last RT dose, is a DLT.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00777894, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2019.

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