A Phase III Study of Pancreatic Cancer

A Randomized Phase III Study of Adjuvant Gemcitabine Versus Gemcitabine Plus Concurrent Chemoradiation in Pancreatic Cancer Underwent Curative Intent (R0 / R1) Resection

Study Design： Adjuvant gemcitabine therapy has been shown to improve recurrence-free survival in pancreatic cancer underwent curative intent resection. This study is to evaluate whether combining concurrent chemo-radiotherapy can further improve the recurrence-free survival benefit of adjuvant gemcitabine chemotherapy in pancreatic cancer underwent curative resection.

Research Objective and Study End Points

1. Primary endpoint： The primary end point is disease free survival.
2. Secondary endpoints： The secondary end points are to evaluate the overall survival, local and distant recurrence rate, and impact on quality of life after adjuvant gemcitabine with or without CCRT in curatively resected pancreatic cancer.

Furthermore, the clinical, pathological and molecular prognostic factors in curatively resected pancreatic cancers will be evaluated.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer

Detailed Description

Treatment plan and Randomization scheme:：

Patients will be randomized after stratification according to pathology report on section margin, tumor size, lymph node metastasis:

Patients who are randomized to Arm 1 will receive adjuvant chemotherapy started within 4-8 weeks after the surgery, and administered at D1, D8 and D15 every 4 weeks for 6 cycles (6 months). Patients who are allocated to Arm 2 will receive sandwich treatment, which comprised of the same adjuvant chemotherapy within 4-8 weeks after the surgery for 3 cycles (3 months), followed by CCRT (start 4-6 weeks after the last dose of 3rd cycle chemotherapy) and then another 3 cycles of gemcitabine monotherapy.

Statistical Consideration:

We anticipate the 2-year disease free survival will increase from 25% to 40% with the incorporation of CCRT into the adjuvant treatment for post-operative pancreatic adenocarcinoma. With a significant level of 0.05, 107 patients will be required for each treatment arm to reach 80% statistical power. Since the drop out rate is approximately 10%, 265 patients will be enrolled to ensure that we will have 214 (107x2) eligible patients in this study. We anticipate that we will recruit roughly 67 patients per year, therefore, patient recruitment will be completed in 4 years.

Randomization scheme:

Histo-/cyto-logically confirmed macroscopic complete resected pancreatic adenocarcinoma

1. The primary end-point is disease free survival.
2. The secondary end-points are overall survival; local and distant control rate, and the quality of life.

3. The clinical and molecular prognostic factors for overall survival.

   • Radiation fields encompass initial main tumor of pancreas only with a safe margin of 1cm. Lymph node regions initially involved with tumor confirmed by excision will be included in the clinical target volume. Elective radiation to uninvolved lymph nodes will not be given.

• Study Type: Observational
• Enrollment (Actual): 147

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Mackay Memorial Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Chang-Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

We anticipate the 2-year disease free survival will increase from 25% to 40% with the incorporation of CCRT into the adjuvant treatment for post-operative pancreatic andenocarcinoma. With a significant level of 0.05,107 patients will be required for each treatment arm to reach 80% statistical power. Since the drop out rate is approximately 10%, 265 patients will be enrolled to ensure that we will have 214(107x2) eligible patients in this study. We anticipate that we will recruit roughly 67 patients per year, therefore, patient recruitment will be completed in 4 years.

Description

A.Eligibility Criteria

1. Patients with pancreatic cancer after curative intent resection.
2. The histology of resected tumor has to be adenocarcinoma.
3. Age 20-75 years.
4. ECOG performance scale 0-1.
5. Patients must have normal organ and marrow function as defined below.
6. The effects of study agents on the developing human fetus at the recommended therapeutic dose are unknown.
7. to sign a written informed consent.
8. Registered within 6 weeks after surgery.
9. Preoperative abdominal CT or MRI with contrast enhancement.

B.Exclusion Criteria

1. Patients with gross residual, macroscopic positive resection margin or distant metastases.
2. Patients may not be receiving any other investigational agents.
3. Patients who have had prior chemotherapy or radiotherapy are not eligible.
4. History of allergic reactions.
5. Patients who had non-curable second primary malignancy.
6. Uncontrolled intercurrent illness including.
7. Pregnant women.
8. receiving immuno-suppressive therapy、anti-coagulants.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
pancreatic cancer; resected pancreatic cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary end-point is recurrence-free survival.	Pancreatic Cancer Disease Committee

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary end-points are overall survival; local and distant control rate, and the quality of life.	Pancreatic Cancer Disease Committee

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Collaborators: National Taiwan University Hospital; Mackay Memorial Hospital; Chang Gung Memorial Hospital; Taipei Veterans General Hospital, Taiwan; National Cheng-Kung University Hospital; Kaohsiung Medical University; Taichung Veterans General Hospital; Kaohsiung Veterans General Hospital.
• Investigators: Principal Investigator: Yu-Lin Lin, M.D., National Taiwan University Hospital; Study Chair: Tsann-Long Hwang, M.D., Chang Gung Memorial Hospital; Principal Investigator: Yu-Wen Tien Tien, Ph.D., National Taiwan University Hospital; Principal Investigator: Yi-Ming Shyr, M.D., Taipei Veterans General Hospital, Taiwan; Principal Investigator: Pin-Wen Lin, M.D, National Cheng-Kung University Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: March 26, 2008
• First Submitted That Met QC Criteria: October 11, 2009
• First Posted (Estimate): October 14, 2009

Study Record Updates

• Last Update Posted (Estimate): May 4, 2016
• Last Update Submitted That Met QC Criteria: May 3, 2016
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Pancreatic Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: T3207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO