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Phase ǀ Study on Pancreatic Cancer Treated by CyberKnife

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02716207
Recruitment Status : Recruiting
First Posted : March 23, 2016
Last Update Posted : December 29, 2020
Information provided by (Responsible Party):
Zhang Huo Jun, Changhai Hospital

Tracking Information
First Submitted Date  ICMJE January 6, 2016
First Posted Date  ICMJE March 23, 2016
Last Update Posted Date December 29, 2020
Study Start Date  ICMJE March 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
The maximum tolerated dose will be determined [ Time Frame: 2 years ]
The maximal tolerated dose will be defined as the dose for which at least 2 patients in 3, or at least 3 patients in 9, will present with a limiting toxicity.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
  • The acute toxicities following SBRT will be determined. [ Time Frame: 1 year ]
    The acute toxicities are determined by RTOG Acute Radiation Morbidity Scoring Criteria.
  • The late toxicities following SBRT will be determined. [ Time Frame: 1 year ]
    The late toxicities are determined by RTOG/EORTC Late Radiation Morbidity
  • Pain intensity will be determined. [ Time Frame: 1 year ]
    Pain intensity is assessed by the numeric rating scales 0-10
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Phase ǀ Study on Pancreatic Cancer Treated by CyberKnife
Official Title  ICMJE Mono-Center Phase ǀ Study on Dose Escalation of Stereotactic Body Radiotherapy (SBRT) Treating Pancreatic Cancer Patients With CyberKnife
Brief Summary The maximum tolerated dose on locally advanced unresectable pancreatic tumor treated with CyberKnife SBRT will be evaluated.
Detailed Description

Pancreatic cancer is the fourth-leading cause of cancer-related death in the world. It is characterized by metastatic spread and local failure and seldom detected in its earlier stages. For locally advanced stage pancreatic cancer, the complete surgical removal is hard to achieve.

Stereotactic body radiotherapy (SBRT) with CyberKnife for unresectable pancreatic tumor is a relatively new treatment option made available because of significant improvements in diagnostic imaging and radiation delivery techniques. Different from the conventional radiotherapy, radiation dose is delivered in fewer fractions and higher fractional doses in SBRT. Gurka (1) reported that 14 patients received SBRT with prescription dose of 25 Gy in five fractions with biologically equivalent doses (BED) of α/β=10 in correspondence to 37.5Gy. Grade 1 to 2 gastrointestinal toxicity (no grade 3 or 4 radiation-related toxicities) was observed two weeks after treatment. Two patients had a partial response, and 12 patients were with stable diseases. In the previous dose escalation study, a single fraction up to15 Gy, 20 Gy, 25 Gy which is an equivalent BED10 to 37.5 Gy, 60 Gy, 87.5 Gy respectively is recommended by Koong AC (2) and his team. Even though the local control rate is 100%, the follow up is short and the sample size of 15 patients is relatively small. Moreover, the late toxicity is not investigated. And with single fraction scheme, higher late gastrointestinal (GI) toxicities were reported (2,3,4). In the meanwhile, investigators (5, 6) from South Korea examined that a Dmax of 35Gy and 38Gy in 3 fractions (BED10 to 75.8Gy and 86.1Gy) of SBRT correlated with a 5% and 10% rate of grade 3 of gastroduodenal toxicity for abdominal malignant tumor, respectively.

Chuong (7) used 5 fractions to potentially decrease the risk of late normal tissue injury compared with 1 to 3 fractions commonly used in other institutions. Assuming α/β=3, the BED3 delivered to normal tissue in this study (using a mean 36.4 Gy in 5 fractions to the high dose PTV) was 125 Gy, which is lower than the mean BED3 from other series, the corresponding values from Boston and Stanford were 153.7 Gy (mean, 32.96 Gy in 3 fractions) and 233.3 Gy (mean, 25Gy in 1 fraction), respectively (8, 9). And a relatively lower incidence of grade ≥3 late adverse effects (5.3% VS 9%) was observed.

Since the treatment modality and dose are still under exploratory stage, we propose to conduct a Phase I study determining the maximum tolerated dose of CyberKnife SBRT on dose escalation for the treatment of locally advanced pancreatic tumor based on a 5 fractions treatment regimen. A prescription dose of 35-47.5 Gy in five fractions was chosen, with an equivalent to the traditional dose of 2 Gy in 25-39 fractions of BED10. And this is assumed to be the safe and effective dose for unresectable pancreatic cancer patients.

Study Procedure:

CyberKnife SBRT body fixation (vacuum-bag) will be used in immobilizing the body, the arms and the legs.

  • Patients will undergo a plain CT as well as an enhanced pancreatic parenchymal CT for radiation treatment planning and target delineation.
  • SBRT will be delivered on CyberKnife with Synchrony Respiratory Tracking system. The tumor will be tracked with implanted fiducial markers by Fiducial Tracking System. Treatment will be delivered in 5 fractions within 1 to 2 weeks at the discretion of the investigator.
  • A body fixation (vacuum-bag) will be used in immobilizing the body, the arms (both arms are along the body) and the legs.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Tumor
Intervention  ICMJE Device: CyberKnife
Radiation Therapy
Study Arms  ICMJE Experimental: Maximal tolerated dose with CyberKnife
SBRT will be delivered in 5 fractions within 1 to 2 weeks by the following schedule: Doses of 7 Gy, 7.5 Gy, 8 Gy, 8.5 Gy, 9 Gy, 9.5 Gy x 5 with BED10 in correspondence to 59.5 Gy, 65.6 Gy, 72 Gy, 78.6 Gy, 85.5 Gy, 92.6 Gy respectively while meeting with normal tissue constraints. A minimum of three patients will be included for each dosage level. And an interval is four weeks between each dose level. In case patient presents III/IV GI toxicity, three additional patients will be included at the same dose level. The Maximal Tolerated Dose will be defined as the dose for which at least 2 patients in 3, or at least 3 patients in 9, will present with a limiting toxicity.
Intervention: Device: CyberKnife
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 17, 2016)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Unresectable pancreatic adenocarcinoma or unsuitable/unwilling for resection which is proved by biopsy.
  • A life expectancy of >3months
  • Eastern Cooperative Oncology Group (ECOG) status ≤2
  • Tumor size < 5 cm
  • Tumor location: Head of pancreas
  • Patients must be able to undergo contrast enhanced CT for planning
  • Absolute neutrophil count (ANC) ≥ 1.5 ×109 cells/L
  • Leukocyte count≥ 3.5 ×109cells/L
  • Platelets ≥ 70×109cells/L
  • Hemoglobin ≥ 8.0 g/dl
  • Albumin > 2.5 g/dL
  • Total bilirubin < 3 mg/dL
  • Creatinine < 2.0 mg/dL
  • INR < 2 (0.9-1.1)
  • Aspartate transaminase (AST) <2.5 × Upper Limit of Normal (ULN )(0-64U/L)
  • Alanine aminotransferase (ALT) <2.5 × ULN(0-64U/L)
  • Both men and women and members of all races and ethnic groups are eligible for this study
  • Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document
  • Tumor markers and lab test should be done less than 1 week before recruitment

Exclusion Criteria:

  • Prior surgery, chemotherapy or radiation for the pancreatic tumor
  • Prior radiotherapy to the upper abdomen, evidence of metastatic disease such as nodal or distant metastases by abdomen CT and chest CT or FDG PET-CT
  • Contraindication to receiving radiotherapy
  • Distance between gross tumor volume (GTV) (lesion) and luminal structures (including liver, stomach, duodenum, small or large bowel) is<5 mm
  • Women who are pregnant
  • Participation in another clinical treatment trial while on study
  • Patients in whom fiducial implantation was not possible
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Qing Shui Wang, M.D +8615618863061
Listed Location Countries  ICMJE China
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02716207
Other Study ID Numbers  ICMJE ChanghaiH001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Zhang Huo Jun, Changhai Hospital
Study Sponsor  ICMJE Changhai Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Huo Jun Zhang, MD., PH.D Changhai Hospital
PRS Account Changhai Hospital
Verification Date September 2020

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