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A Phase II Randomized Study of Induction Chemotherapy Followed by Concurrent Chemo-radiotherapy in Locally Advanced Pancreatic Cancer

Phase 2
20 Years
70 Years
Open (Enrolling by invite only)
Pancreatic Cancer

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Trial Information

A Phase II Randomized Study of Induction Chemotherapy Followed by Concurrent Chemo-radiotherapy in Locally Advanced Pancreatic Cancer

Patients should be randomized to two study arms stratified by resectability status
(borderline resectable and unresectable) after enrollment. Eligible patients will be
randomly assigned on a 1:1 basis to either of two study groups, using a central
randomization procedure with stratification according to NCCN criteria of resectability.

After randomization, induction chemotherapy (ICT) will be administered for 3 cycles (3
months). Patients who have radiological evidence of distant dissemination will be shifted to
salvage chemotherapy. Patients who have responsive, stable disease as well as those with
localized progressive disease after ICT will receive concurrent chemoradiotherapy (CCRT) 3-4
weeks after the last dose of ICT. Surgical evaluation will be performed 4-6 weeks after the
completion of CCRT. Patients who have respectable disease will undergo surgical resection.
Postoperative adjuvant chemotherapy for 3 cycles (3 months) will be given for those who are
considered to have curative resection. Patients who still have unresectable disease or
non-curative resection will receive systemic chemotherapy till disease progression or
unacceptable toxicity.

For Arm 1, ICT with FOLFIRINOX ( oxaliplatin 85mg/m2 for 2 hr, irinotecan 180mg/m2 for 90
min and 5FU 3000mg/m2 + LV 150mg/m2 continuous infusion 48 hr) will be administered
biweekly. For Arm 2, ICT with GOFL ( 800mg/m2 gemcitabine at a fixed rate of 10mg/m2/min
followed by a 2-hour oxaliplatin 85mg/m2 and then a 48-hour 3000mg/m2 5-FU and 150 mg/m2
leucovorin on day 1 and 15 every 28 days/cycle) will be given biweekly.

After three 3 cycles of ICT, patients without distant metastasis will be given CCRT with
5-FU 450mg/m2 in Arm 1, gemcitabine 400mg/m2 in Arm 2, 2 hrs before RT on
day1,8,15,22,29,36. Radiation will be given 180cGy per day, 5 days a week for 28 fractions
to totally 5040cGy.

If complete surgical resection is feasible, optimal surgery will be performed 4-6 weeks
after CCRT. If complete surgical resection is impossible, biopsy with or without bypass
surgery may be performed. Patients who have curative surgical resection will receive
additional 6 cycles ( 6 months) of adjuvant chemotherapy ( Arm1, FOLFIRINOX, Arm 2, GOFL)
within 4 weeks after surgery and then followed up until tumor progression. Patients who are
not feasible for curative resection, will receive continued chemotherapy (Arm1, FOLFIRINOX;
Arm2, GOFL) 3-4 weeks after CCRT complete. The regimen will continue till disease

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed adenocarcinoma of the
exocrine pancreas.

2. Patients must have locally advanced pancreatic cancer (LAPC).

3. Patients must have LAPC evaluated by radiologist and/or surgeon according to either
abdominal CT or MRI, or intra-operative findings.

- Locally advanced unresectable disease was defined by CT or MRI images as
low-density tumor (primary and/or lymphadenopathy) with

1. extension to the celiac axis or superior mesenteric artery,

2. occlusion of the superior mesenteric-portal venous confluence

3. aortic, inferior vena cava (IVC) invasion or encasement

4. invasion of SMV below transverse mesocolon or unresectable after surgical

Those who had superior mesenteric vein impingement, superior mesenteric artery
abutment were defined as borderline resectable.

Those who had superior mesenteric vein occlusion, superior mesenteric artery
encasement were defined as unresectable.

4. Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan. See section 8.2
for the evaluation of measurable disease.

5. Age >20 years and ≦70 years.

6. ECOG performance score of 0 or 1; see Appendix A.

7. Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count >1,500/mL

- platelets >100,000/mL

- total bilirubin <1.5X institutional upper limit of normal

- ALT(SGPT) <5 X institutional upper limit of normal

- creatinine within normal institutional limits or creatinine clearance>60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal

8. Patients who present with jaundice will be allowed to enroll after control with
temporary or permanent internal/external drainage.

9. The effects of study agents on the developing human fetus at the recommended
therapeutic dose are unknown. Women of child-bearing potential and men must agree to
use adequate contraception (hormonal or barrier method of birth control; abstinence)
prior to study entry and for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately.

10. Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

1. Patients with distant metastases are not eligible.

2. Patients with endocrine or acinar pancreatic carcinoma.

3. Patients may be receiving any steroid, immunologic or other investigational agents
within 4 weeks prior to enrollment.

4. Patients who have had prior chemotherapy or radiotherapy are not eligible.

5. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to study agents used in the study.

6. Patients who have above grade II peripheral neuropathy.

7. Patients who had non-curable second primary malignancy within five years, except for
non-melanoma skin cancer.

8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

9. Pregnant women are excluded from this study because the study agents has the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with study agents, breastfeeding should be discontinued if the mother is
treated with the study agents.

10. Those who are immuno-compromised or receiving immuno-suppressive therapy are excluded
from the study because of increased risk of lethal infections and possible
pharmacokinetic interactions with study agent administered during the study.

11. Those who have chronic diarrhea.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

the response rate, disease control rate, overall survival, and patients' quality of life.

Outcome Description:

This is a randomized phase II trial of ICT followed by CCRT with radiotherapy in LAPC. The efficacy will be primarily measured by progression free survival (PFS) as defined in Section 8.5.Other measurements include the response rate, disease control rate, overall survival, and patients' quality of life as described in Section 8.We anticipate that the attrition rate is about 10%, hence, roughly 86 patients will be recruited , we anticipate that the recruitment will be completed in 4.5 years.

Outcome Time Frame:

4.5 years

Safety Issue:


Principal Investigator

Yen-Shen Shen, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cheng-Kung University Hospital


Taiwan: Department of Health

Study ID:




Start Date:

June 2013

Completion Date:

May 2019

Related Keywords:

  • Pancreatic Cancer
  • Locally Advanced Pancreatic Cancer
  • Pancreatic Neoplasms