Combination of SBRT With Sequential S-1 for Treating Locally Advanced Pancreatic Cancer

September 22, 2020 updated by: Zhang Huo Jun, Changhai Hospital

Stereotactic Body Radiation Therapy With Sequential S-1 for Patients With Locally Advanced Pancreatic Cancer and Poor Medical Conditions --a Phase II Clinical Trial

The safety and efficacy of combination of SBRT with sequential S-1 in treating patients with locally advanced pancreatic cancer and poor medical conditions will be evaluated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Although the incidence rate of pancreatic cancer is not as high as that of other gastrointestinal carcinoma in China, the cancer mortalities of males and females ranked the sixth and seventh respectively in 2013, with a surprising low 5-year survival rate (<5%). Only 15%-20% patients are suitable for surgeries among those first diagnosed with pancreatic cancer and the 5-year survival rate of patients with R0 resection is still less than 20%.

Therefore, better efficacy is not available via surgeries alone resulting in great emphasis on adjuvant chemoradiotherapy. In 1997, gemcitabine was confirmed to be the standard chemotherapy for pancreatic cancer. However, it has not been proved that gemcitabine significantly improved prognosis in long term follow-up while some patients are refractory to gemcitabine. Hence, development of more effective chemotherapy is urgent.

S-1 is the prodrug of 5-fluorouracil (5-FU), comprised of tegafur, gimeracil (dihydropyrimidine dehydrogenase inhibitor) and oteracil (the inhibitor of phosphorylation in gastrointestinal tract) with a ratio of 1:0.4:1. The first phase II clinical trials showed good clinical efficacy with S-1.Moreover, Ueno et al. identified better objective response rates with S-1 than those with gemcitabine. Besides, S-1 is not inferior to gemcitabine regarding to overall survival rates and progression free survival rates. And significant improvement of progression free survival rates can be achieved by combination of S-1 and gemcitabine. There was no difference between incidence rates of adverse effects of S-1 and gemcitabine, with more gastrointestinal toxicities with S-1 while more hematologic toxicities with gemcitabine. Therefore, S-1 is an alternative for treating locally advanced or metastatic pancreatic cancer, especially for those resistant to gemcitabine. Although there are no phase III studies on S-1, phase II studies have already shown better disease control rates (52%-58%), median overall survival time (4.5-6.3 months) and tolerable adverse effects in advanced pancreatic cancer resistant to gemcitabine treated with S-1.

Though S-1 is appropriate for advanced pancreatic cancer, it is not superior to gemcitabine with respect to clinical efficacy. In addition, fewer encouraging results are gained with combination of S-1 and other drug. As a result, S-1 combined with radiotherapy is gradually applied in treatment of pancreatic cancer.

5-FU was proved to be radiosensitive thus improving clinical efficacy. S-1 combined with radiotherapy has demonstrated better prognosis with the median overall survival time of 12.9-16.8 months. Furthermore, some patients can be operable after S-1 and radiotherapy.

Compared with conventional radiation, a single-fraction dose and total dose of target volume can be increased in stereotactic body radiation therapy (SBRT). In addition, doses of organs at risk would be reduced, thus effectively improving local control rates and reducing radiation related toxicity. Shorter courses of SBRT also enhance patients' compliance and render the initial of other treatment on schedule possible. Nevertheless, there are few studies focusing on S-1 combined with SBRT for locally advanced pancreatic cancer. Especially for patients with poor medical coonditions, though gemcitabine alone is recommended in the NCCN guideline, S-1 may be a better option due to more adverse effects induced by gemcitabine in Asian. Additionally, local ablative treatment combined with chemotherapy may provide more survival benefits for those patients. Hence, efficacy of combination of S-1 and SBRT needs to be further confirmed. Based on our experience in treating locally advanced pancreatic cancer, SBRT combined with sequential S-1 as the initial treatment for patients with locally advanced pancreatic cancer and poor medical conditions is proposed to evaluate its clinical efficacy.

Study Procedure:

  1. 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.
  2. 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.
  3. A body fixation (vacuum-bag) will be used in immobilizing the body, the arms (both arms are along the body) and the legs.
  4. The total doses depend on patients' medical conditions, ranging from 35Gy-40Gy/5Fx.
  5. Patients receive 80 mg of S-1 per square meter of body surface area twice a day for 4 weeks, followed by 2 weeks of rest as one course, which would repeat for six cycles.The initiation of S-1 is one month after SBRT.

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200433
        • Changhai Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Locally advanced pancreatic cancer proved by CT or MRI and biopsy
  2. Without any other treatment before SBRT
  3. A life expectancy of >3months
  4. ECOG: 2 or 3 points
  5. Age of more than 18 years old
  6. Blood routine examination: Absolute neutrophil count (ANC) ≥ 1.5 ×10^9 cells/L, leukocyte count≥ 3.5 ×10^9 cells/L, platelets ≥ 70×10^9 cells/L, hemoglobin ≥ 8.0 g/dl
  7. Liver and kidney function tests: Albumin > 2.5 g/dL, total bilirubin < 3 mg/dL, creatinine < 2.0 mg/dL, AST<2.5 × ULN(Upper Limit of Normal)(0-64U/L), ALT<2.5 × ULN(0-64U/L)
  8. INR < 2 (0.9-1.1)
  9. Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Prior surgery, chemotherapy or radiation for the pancreatic cancer
  2. Evidences of metastatic disease such as nodal or distant metastases by abdomen CT and chest CT or FDG PET-CT
  3. Contraindication to receiving radiotherapy
  4. ECOG: 0-1 point
  5. Age<18
  6. Abnormal results of blood routine examinations and liver and kidney tests
  7. Patients with active inflammatory bowel diseases or peptic ulcer
  8. Gastrointestinal bleeding or perforation within 6 months
  9. Heart failure: NYHA III-IV
  10. Women who are pregnant
  11. Participation in another clinical treatment trial while on study
  12. Patients in whom fiducial implantation was not possible
  13. Inability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination of Cyberknife with S-1
Patients with locally advanced pancreatic cancer meeting all inclusion criteria will receive combination of Cyberknife with S-1.
Other: combination of Cyberknife with S-1
Radiation therapy combined with chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
One-year Overall Survival Rate
Time Frame: 1 year
One-year overall survival rate is calculated by the ratio of number of patients surviving more than 1 year to the total number of patients enrolled.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Acute Toxicities Following SBRT
Time Frame: Within 90 days after completion of SBRT
The acute toxicities are determined by RTOG Acute Radiation Morbidity Scoring Criteria.
Within 90 days after completion of SBRT
Number of Participants With Late Toxicities Following SBRT
Time Frame: 90 days after SBRT
The late toxicities are determined by RTOG/EORTC Late Radiation Morbidity Scoring Criteria.
90 days after SBRT
The Median Progression Free Survival Time Will be Determined.
Time Frame: 3 years
Progression-free survival is the time from the date of enrollment to the confirmation of disease progression at any sites, including local progression or metastasis, or death from any causes, if this occurred before disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
3 years
The Quality of Life Will be Analyzed.
Time Frame: 1 years
The analysis of quality of life is based on The European Organization for Reasearch and Treatment of Cancer (EORTC): Quality of Life Questionnare-Core 30 (QLQ-C30). Higher scores in function domains and global health status indicate better quality of life, while higher scores in symptom domains imply worse quality of life. The scale range of all domains of QLQ-C30 is 0-100 (the minimum and maximum score is 0 and 100 points, respectively).
1 years
Median Overall Survival Will be Determined.
Time Frame: 3 years
Median overall survival is calculated by Kaplan-Meier method.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Changhai Hospital

Investigators

  • Principal Investigator: Huo Jun Zhang, MD., PH.D, Changhai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2016

Primary Completion (Actual)

May 1, 2020

Study Completion (Actual)

May 1, 2020

Study Registration Dates

First Submitted

March 1, 2016

First Submitted That Met QC Criteria

March 4, 2016

First Posted (Estimate)

March 9, 2016

Study Record Updates

Last Update Posted (Actual)

October 19, 2020

Last Update Submitted That Met QC Criteria

September 22, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Changhai Hosp

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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