Clinical trial NCT00994721: A Phase III Study of Pancreatic Cancer
Official title: A Randomized Phase III Study of Adjuvant Gemcitabine Versus Gemcitabine Plus Concurrent Chemoradiation in Pancreatic Cancer Underwent Curative Intent (R0 / R1) Resection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pancreatic Cancer
Keywords: Pancreatic Cancer
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital
name: Chang Gung Memorial Hospital
name: Taipei Veterans General Hospital, Taiwan
name: Mackay Memorial Hospital
name: Taichung Veterans General Hospital
name: National Cheng-Kung University Hospital
name: Kaohsiung Veterans General Hospital.
name: Kaohsiung Medical University
First posted: 2009-10-14
Enrollment: 147
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The primary end-point is recurrence-free survival.
timeFrame: Pancreatic Cancer Disease Committee
Secondary outcomes:
measure: The secondary end-points are overall survival; local and distant control rate, and the quality of life.
timeFrame: Pancreatic Cancer Disease Committee
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Chang-Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Tsann-Long Hwang, M.D.
role: STUDY_CHAIR
affiliation: National Taiwan University Hospital
name: Yu-Wen Tien Tien, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Taipei Veterans General Hospital, Taiwan
name: Yi-Ming Shyr, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cheng-Kung University Hospital
name: Pin-Wen Lin, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Yu-Lin Lin, M.D.
role: PRINCIPAL_INVESTIGATOR
References: