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CyberKnife® for Hepatic Metastases From Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01318447
Recruitment Status : Terminated (Lack of enrollment)
First Posted : March 18, 2011
Last Update Posted : April 8, 2013
Sponsor:
Collaborator:
Centre Oscar Lambret
Information provided by (Responsible Party):
Accuray Incorporated

Tracking Information
First Submitted Date  ICMJE March 16, 2011
First Posted Date  ICMJE March 18, 2011
Last Update Posted Date April 8, 2013
Study Start Date  ICMJE January 2011
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2011)
Local recurrence-free survival [ Time Frame: 12 months ]
Local hepatic control (non progression: complete response, partial response or stable disease) will be assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Local recurrence-free survival time is calculated as the time between the date of first treatment session and the date of the first local recurrence. Patients alive who never experienced local recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than local recurrence at the time of analysis are censored at the date of death.
Original Primary Outcome Measures  ICMJE
 (submitted: March 17, 2011)
Local recurrence-free survival [ Time Frame: 12 months ]
Local hepatic control (non progression: complete response, partial response or stable disease) will be assessed according to RECIST1.1 criteria. Local recurrence-free survival time is calculated as the time between the date of first treatment session and the date of the first local recurrence. Patients alive who never experienced local recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than local recurrence at the time of analysis are censored at the date of death.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2011)
  • Recurrence-free survival [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    Recurrence-free survival time is calculated as the time between the date of first treatment session and the date of a local or distant recurrence or death from progression whichever comes first. Patients alive who never experienced recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than cancer are censored at the date of death.
  • Overall survival [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    Overall survival time is calculated as the time between the date of first treatment session and the date of death, whatever the cause. Patients alive at the time of analysis are censored at the date of the last follow-up visit.
  • Acute and long term toxicity [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be used for toxicity assessment.
  • Quality of Life [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    • European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) measures the quality of life for patients with cancer (for all participating sites).
    • Quality of Life Questionnaire-Liver Metastases Colorectal (QLQ-LMC21) is a specific module developed by the EORTC for patients with colorectal liver metastases (for sites in the United Kingdom, The Netherlands, Germany, France, and Belgium (French speaking part)).
  • Correlation of response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) [ Time Frame: 6, 18 and 24 months ]
    The PERCIST response criteria will be applied to patients who have tumor characteristics measured by a PET-Scan. The association of response according to RECIST 1.1 and PERCIST will be evaluated with Spearman's correlation coefficient and the kappa statistic.
  • Local recurrence-free survival [ Time Frame: 3, 6, 9, 18 and 24 months ]
    Local hepatic control (non progression: complete response, partial response or stable disease) will be assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Local recurrence-free survival time is calculated as the time between the date of first treatment session and the date of the first local recurrence. Patients alive who never experienced local recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than local recurrence at the time of analysis are censored at the date of death.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2011)
  • Recurrence-free survival [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    Recurrence-free survival time is calculated as the time between the date of first treatment session and the date of a local or distant recurrence or death from progression whichever comes first. Patients alive who never experienced recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than cancer are censored at the date of death.
  • Overall survival [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    Overall survival time is calculated as the time between the date of first treatment session and the date of death, whatever the cause. Patients alive at the time of analysis are censored at the date of the last follow-up visit.
  • Acute and long term toxicity [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be used for Toxicity assessment.
  • Quality of Life [ Time Frame: 3, 6, 9, 12, 18 and 24 months ]
    • EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30 questionnaire measures the quality of life for patients with cancer (for all participating sites).
    • LMC21 is a specific module developed by EORTC for patients with colorectal liver metastases (for sites in the UK, The Netherlands, Germany, France, and Belgium (French speaking part)).
  • Correlation of response as assessed by RECIST 1.1 and PERCIST [ Time Frame: 6, 18 and 24 months ]
    The PERCIST response criteria will be applied to patients who have tumor characteristics measured by a PET-Scan. The association of response according to RECIST 1.1 and PET-Scan treatment response (PERCIST) will be evaluated with Spearman's correlation coefficient and the kappa statistic.
  • Local recurrence-free survival [ Time Frame: 3, 6, 9, 18 and 24 months ]
    Local hepatic control (non progression: complete response, partial response or stable disease) will be assessed according to RECIST1.1 criteria. Local recurrence-free survival time is calculated as the time between the date of first treatment session and the date of the first local recurrence. Patients alive who never experienced local recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than local recurrence at the time of analysis are censored at the date of death.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CyberKnife® for Hepatic Metastases From Colorectal Cancer
Official Title  ICMJE International, Phase II Study of CyberKnife® for Hepatic Metastases From Colorectal Cancer
Brief Summary This prospective, multicenter study is intended to establish the efficacy and toxicity of treating unresectable colorectal liver metastases with accurately administered radiation using the CyberKnife stereotactic radiosurgery system.
Detailed Description

Colorectal cancer is the fourth most commonly diagnosed malignant disease worldwide, with an estimated 1,023,000 new cases and 529,000 deaths each year. The liver is the most frequent site of metastatic spread from colorectal cancer, 25% of colorectal cancer patients will have liver metastases at the time of initial colorectal resection and more than 50% of colorectal cancer patients will develop liver metastases during the course of the disease.

The current standard of care and only potential curative therapy for colorectal liver metastases is liver resection of the metastatic lesions. Surgical resection provides long term survival in patients with colorectal carcinoma (CRC) liver metastases. In a report of 1001 patients with metastatic colorectal cancer from Memorial Sloan-Kettering Cancer Center in NY, USA, surgical resection of liver metastases resulted in 3- and 5-year survival rates of 37% and 22%, respectively. Advances in pre- and intra-operative imaging and chemotherapy during recent years have increased overall survival up to 60% at 5 years after liver resection. However, 80-90% of liver metastases are unresectable at the time of diagnosis usually due to tumor location, multifocality, inadequate functional hepatic reserve or the patient's overall condition. For those patients, harboring unresectable liver metastases, alternative treatment approaches include neoadjuvant chemotherapy, local ablation therapy and stereotactic radiation therapy.

The recent availability of neoadjuvant chemotherapeutic agents has increased the response rates and doubled the median overall survival time for metastatic colorectal cancer from 10 to 20 months. Recent studies have demonstrated that neoadjuvant therapy allows 12.5% of patients with unresectable CRC liver metastases to be significantly downstaged and eligible for hepatic resection.

For unresectable CRC liver metastases, local ablative therapies are widely applied. Local ablative treatment refers to a variety of intervention techniques that specifically target tumors to directly destroy them. Numerous methods of ablation have been developed including cryoablation, percutaneous ethanol injection, radiofrequency ablation (RFA) and stereotactic radiation therapy. The most widely employed non-radiation based local ablative treatment is RFA which induces thermal ablation by passing high-frequency alternating current through the tumor utilizing electrodes that are placed within the tumor and surrounding tissue. RFA can be applied percutaneously under ultrasonic guidance or directly during laparoscopy or open laparotomy. Local recurrence rates of 44.4% at 18 months were reported by Solbiati et al. for CRC liver metastases with a median diameter of 2.6 cm. For tumors greater than 4 cm the local recurrence rate was 68%. RFA has an overall 3-year survival rate of 28-46% and a 5-year survival rate of 25%. However, patients with advanced hepatic decompensation, large tumors (3 to 5 cm), or multifocal tumors are generally considered poor candidates for RFA.

Conventional radiation therapy has been shown useful for palliation of hepatic capsular pain, but historically it has played a minor role in the treatment of patients with unresectable liver metastases. This can be attributed chiefly to the low tolerance of the whole liver to radiation. The liver was thought to be a relatively radiosensitive organ and with whole liver irradiation, it was difficult to achieve the radiation doses necessary to eradicate gross tumors without causing radiation induced liver disease. Partial liver irradiation has shown some promise. Limiting irradiation to only one-third of the liver through three-dimensional (3D) conformal radiotherapy techniques, including intensity modulated radiotherapy (IMRT), several studies have shown that partial liver irradiation is safe with doses up to 50-72.6 Gy. However, further dose escalation with conventional radiation therapy techniques risks injury to adjacent abdominal organs.

Stereotactic Body Radiation Therapy (SBRT) has emerged as a novel approach for the local ablation of liver metastases. SBRT provides a conformal isodose distribution with a steep radiation dose gradient allowing much higher doses of radiation than conventional radiation therapy and conformal radiotherapy techniques to be delivered safely with high precision to focal liver metastases while minimizing the radiation dose to normal liver and adjacent organs. To achieve this, precise localization of the target during treatment is required which necessitates accounting for tumor motion. SBRT technology utilizes a number of techniques to accommodate for tumor and respiratory motion including motion-restrictive techniques such as frames and abdominal compression, as well as motion-compensating techniques such as active breathing control and tumor tracking. The motion-restrictive techniques can be difficult for some patients to withstand, limiting those patients from being able to receive treatment. The motion-restrictive techniques can also necessitate the use of wide margins. Rusthoven et al. found a gross tumor volume (GTV) to planning target volume (PTV) expansion of up to 15 mm necessary in the craniocaudal direction. Wide margins can result in irradiation of a substantial volume of normal liver, potentially increasing the risk of radiation-induced injury. Some studies suggest the motion-compensating approach of active breathing control can aid in reducing the margins required by motion-restrictive approaches, however, Korreman et al. suggest those reductions may only be applicable with the use of image-guidance between and within sessions.

The CyberKnife robotic radiosurgery system (Accuray Incorporated, Sunnyvale, CA) an advanced platform to deliver SBRT, provides a therapeutic solution to this problem by continuously tracking the tumor during treatment while it accounts for organ motion due to respiratory movement, using the Synchrony respiratory tracking system (Accuray Incorporated, Sunnyvale, CA). Utilizing continuous tumor tracking, margin expansion to account for motion uncertainty can be reduced, having the potential to make this a safe and effective treatment. The frameless nature of the CyberKnife and its continuous image guidance system eliminates the need of motion-restriction techniques increasing the comfort and availability of the treatment to patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Liver Metastases
Intervention  ICMJE Radiation: CyberKnife SBRT
Dose is 45 Gy (15 Gy in 3 fractions) and delivered over 5 to 10 days.
Study Arms  ICMJE Experimental: CyberKnife SBRT
Intervention: Radiation: CyberKnife SBRT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 5, 2013)
15
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2011)
72
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or Female
  • Hepatic metastases from histologically confirmed colorectal adenocarcinoma
  • 3 hepatic lesions or less present
  • Cumulative size of hepatic lesions between 1 and 10 cm
  • Treatment determined by the liver/GI tumor board or equivalent organization at the participating site
  • Metastatic disease not amenable to surgery as assessed by the panel (including a surgeon) or patient who refuses surgery
  • Patient must be able to undergo contrast enhanced CT for planning
  • Age >= 18 years old
  • Performance Status (ECOG) ≤ 2
  • Minimum of 6 months between the initial diagnosis of the disease and the first hepatic metastasis
  • Minimum of 4 weeks between prior chemotherapy or targeted therapy and the first CyberKnife session
  • Total bilirubin ≤ 3 times the upper limit of normal, ASAT and ALAT ≤ 5 times the upper limit of normal
  • Albumin >= 36 g/L and lymphocytes >= 700/mm3
  • No contraindication to fiducials implantation, hemostasis problems shall be corrected before implantation
  • Life expectancy >= 3 months
  • Patient affiliated with a health insurance system. Applicable for French patients only.
  • Patient having signed the informed consent

Exclusion Criteria:

  • Prior abdominal radiation therapy
  • Any evidence of visible intra-hepatic bile duct dilatation on pre-treatment images
  • Extrahepatic metastases
  • Current evidence of ascitis
  • Renal insufficiency (creatinine clearance < 45 ml/min)
  • Known allergy to gold
  • Pregnant or lactating woman
  • Prior history of other cancer except basocellular carcinoma and in situ cervix carcinoma
  • Patient already enrolled in another therapeutic clinical trial
  • Inability to comply with follow-up visits for geographical, social or psychological reasons
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   United Kingdom
Removed Location Countries Canada,   United States
 
Administrative Information
NCT Number  ICMJE NCT01318447
Other Study ID Numbers  ICMJE ACC-HM-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Accuray Incorporated
Study Sponsor  ICMJE Accuray Incorporated
Collaborators  ICMJE Centre Oscar Lambret
Investigators  ICMJE
Principal Investigator: Xavier Mirabel, MD Centre Oscar Lambret
PRS Account Accuray Incorporated
Verification Date April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP