Combination Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer

NCT ID: NCT00089024

Last Updated: 2023-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-25
• Study Completion Date: 2014-12-01

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients who may undergo surgery for locally advanced pancreatic cancer.

Detailed Description

OBJECTIVES:

• Determine the antitumor and clinical benefit response to neoadjuvant chemoradiotherapy comprising gemcitabine, fluorouracil, leucovorin calcium, and oxaliplatin in patients with potentially resectable locally advanced adenocarcinoma of the pancreas.
• Determine the toxic effects of this regimen in these patients.
• Determine the achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients and correlate these plasma levels with clinical toxicity associated with this regimen.
• Determine the potential importance of polymorphic variations in genomic DNA of pertinent genes (whose protein products are targets of the antineoplastic drugs used in this study) on response to and toxicity of this regimen in these patients.
• Determine the gene expression profiles of primary and metastatic pancreatic tumors before and after treatment with this regimen.

OUTLINE:

• Neoadjuvant chemotherapy: Patients receive gemcitabine IV over 30 minutes and fluorouracil IV continuously over 24 hours on days 2 and 9, and leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
• Neoadjuvant chemoradiotherapy: Beginning on day 42, patients undergo chemoradiotherapy comprising oxaliplatin IV over 2 hours on days 42, 49, 56, 63, 70, and 77 and fluorouracil IV continuously on days 42-78 with external beam radiotherapy.
• Surgery: Patients undergo surgical resection 42-56 days after completion of chemoradiotherapy.
• Adjuvant chemotherapy: After post-operative recovery, patients receive 2 additional courses of gemcitabine, fluorouracil, and leucovorin calcium. If surgical resection is not possible, patients with stable or responsive disease resume gemcitabine, fluorouracil, and leucovorin calcium indefinitely in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment

see interventions

Group Type: EXPERIMENTAL

fluorouracil

Intervention Type: DRUG

2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 \& 2; Repeat one 3-week cycle starting day 22

gemcitabine hydrochloride

Intervention Type: DRUG

750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 \& 2; Repeat one 3-week cycle starting day 22

leucovorin calcium

Intervention Type: DRUG

20 mg/m5 PO (day 1) and 20 mg/m5 IV (day 2) weeks 1 and 2; Repeat one 3-week cycle starting day 22

oxaliplatin

Intervention Type: DRUG

48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5

adjuvant therapy

Intervention Type: PROCEDURE

Patients who have undergone surgical resection, after post-operative recovery, will receive two additional cycles of gemcitabine/5-FU/leucovorin. Patients will then be followed at 3 month intervals with a history and physical exam, CT scan of the chest/abdomen/pelvis, and tumor markers.

If surgical resection is not possible, patients with stable or responsive disease will resume gemcitabine/5-FU/leucovorin and continue on it indefinitely until disease progression provided the patient tolerates it and wishes to remain on therapy.

conventional surgery

Intervention Type: PROCEDURE

Restaging with repeat imaging studies will be performed four weeks after completion of the chemo-radiation. If no contraindication for surgical resection is identified, resection will be performed six to eight weeks after completing chemoradiation. At the time of surgical resection, an extensive examination of the abdomen will be performed to exclude the presence of metastatic disease. All operations will be performed with curative intent with resection of all gross tumor (ie R0 \[negative margins\] or R1 \[positive microscopic margins\]). Resection of adjacent involved organs or vascular structures will be performed as clinically indicated.

neoadjuvant therapy

Intervention Type: PROCEDURE

Eligible patients will receive an initial two cycles of chemotherapy with gemcitabine 750 (females) or 900 (males) mg/m5 over 30 minutes followed by a 24-hour infusion of fluorouracil 2700 mg/m5 on days 2 and 9 of a 21-day cycle . Calcium leucovorin 20 mg/m5 will be given orally on days 1 and 8 and by IV push on days 2 and 9 prior to the 5-FU. A window of -2 up to +7 days will be allowed to start planned cycles of therapy provided all other criteria to restart the new cycle has been met. Patients will require a central venous catheter (Port, Hickman or Groshong catheter) for the administration of 5-FU.

radiation therapy

Intervention Type: RADIATION

A re-staging CT scan, which will be obtained as part of the radiation simulation, will be used to assess any possible response to the initial two cycles of chemotherapy. Unless the patient has developed evidence of metastatic disease, chemoradiation will proceed. Patients who required no treatment delays will commence chemoradiation on day 42. If a one-week delay is needed before cycle 2 of neo-adjuvant chemotherapy can be delivered, the patient will begin chemoradiation on day 49 provided treatment-related toxicity has resolved. If cycle 2 could not be given (2 or more week delay for resolution of treatment-related toxicity), then chemoradiation will begin once toxicity has resolved (may be earlier than day 42).

Interventions

fluorouracil

2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 \& 2; Repeat one 3-week cycle starting day 22

Intervention Type: DRUG

gemcitabine hydrochloride

750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 \& 2; Repeat one 3-week cycle starting day 22

Intervention Type: DRUG

leucovorin calcium

20 mg/m5 PO (day 1) and 20 mg/m5 IV (day 2) weeks 1 and 2; Repeat one 3-week cycle starting day 22

Intervention Type: DRUG

oxaliplatin

48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5

Intervention Type: DRUG

adjuvant therapy

Patients who have undergone surgical resection, after post-operative recovery, will receive two additional cycles of gemcitabine/5-FU/leucovorin. Patients will then be followed at 3 month intervals with a history and physical exam, CT scan of the chest/abdomen/pelvis, and tumor markers.

If surgical resection is not possible, patients with stable or responsive disease will resume gemcitabine/5-FU/leucovorin and continue on it indefinitely until disease progression provided the patient tolerates it and wishes to remain on therapy.

Intervention Type: PROCEDURE

conventional surgery

Restaging with repeat imaging studies will be performed four weeks after completion of the chemo-radiation. If no contraindication for surgical resection is identified, resection will be performed six to eight weeks after completing chemoradiation. At the time of surgical resection, an extensive examination of the abdomen will be performed to exclude the presence of metastatic disease. All operations will be performed with curative intent with resection of all gross tumor (ie R0 \[negative margins\] or R1 \[positive microscopic margins\]). Resection of adjacent involved organs or vascular structures will be performed as clinically indicated.

Intervention Type: PROCEDURE

neoadjuvant therapy

Eligible patients will receive an initial two cycles of chemotherapy with gemcitabine 750 (females) or 900 (males) mg/m5 over 30 minutes followed by a 24-hour infusion of fluorouracil 2700 mg/m5 on days 2 and 9 of a 21-day cycle . Calcium leucovorin 20 mg/m5 will be given orally on days 1 and 8 and by IV push on days 2 and 9 prior to the 5-FU. A window of -2 up to +7 days will be allowed to start planned cycles of therapy provided all other criteria to restart the new cycle has been met. Patients will require a central venous catheter (Port, Hickman or Groshong catheter) for the administration of 5-FU.

Intervention Type: PROCEDURE

radiation therapy

A re-staging CT scan, which will be obtained as part of the radiation simulation, will be used to assess any possible response to the initial two cycles of chemotherapy. Unless the patient has developed evidence of metastatic disease, chemoradiation will proceed. Patients who required no treatment delays will commence chemoradiation on day 42. If a one-week delay is needed before cycle 2 of neo-adjuvant chemotherapy can be delivered, the patient will begin chemoradiation on day 49 provided treatment-related toxicity has resolved. If cycle 2 could not be given (2 or more week delay for resolution of treatment-related toxicity), then chemoradiation will begin once toxicity has resolved (may be earlier than day 42).

Intervention Type: RADIATION

Other Intervention Names

Tolak, Fluoroplex, Carac; Gemzar; folic acid analog; chemotherapy

Eligibility Criteria

Inclusion Criteria

• Diagnosis of adenocarcinoma of the pancreas

o Locally advanced disease

• Potentially resectable disease
• 19 years of age and over
• Karnofsky 60-100%
• Absolute granulocyte count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 2.0 mg/dL (in the absence of biliary obstruction)

• If biliary obstruction is present, patients must undergo biliary decompression
• Bilirubin ≤ 3.0 mg/dL after biliary drainage has been established
• Creatinine ≤ 1.6 mg/dL

Exclusion Criteria

• No early stage resectable disease
• No concurrent non-steroidal anti-inflammatory medication
• No evidence of distant metastases to the liver or peritoneal area according to imaging studies and laparoscopic staging
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No serious uncontrolled cardiac arrhythmia
• Not pregnant or nursing
• No uncontrolled illness
• No active or ongoing infection requiring IV antibiotics
• No marked intolerance to 5-fluoropyrimidines (i.e., fluorouracil, floxuridine, capecitabine, or fluorocytosine)
• No allergy to sulfonamides, aspirin, or non-steroidal anti-inflammatory drugs
• No allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with study chemotherapy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinoma
• No prior chemotherapy for pancreatic cancer
• No prior abdominal radiotherapy

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean L Grem, MD

Role: STUDY_CHAIR

University of Nebraska

Locations

Eppley Cancer Center, University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0035-04-FB

Identifier Type: -

Identifier Source: org_study_id