Hypofractionated Stereotactic Body Radiation & Fluorouracil or Capecitabine for Locally Advanced Pancreatic Cancer

NCT03073785 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 0552-16-FBNCI-2016-01360P30CA036727
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer, most commonly adenocarcinoma, is the fourth leading cause of cancer death in the United States. The mainstay of management centers on surgical resection (if resectable) and although low (15% to 20%), resectability rates are associated with dismal survival. An estimated 80% to 85% of the patients recur after surgical resection, leading to a median survival of 20 to 24 months and potentially even less depending on lymph nodal involvement or positive margins. The rationale for utilizing neoadjuvant therapy, commonly fluoropyrimidine-based or gemcitabine based chemotherapy or Chemoradiotherapy (CRT), involves possibly down staging borderline resectable and unresectable patients, potentially making them resectable candidates. This randomized phase II trial will study how well hypofractionated stereotactic body radiation therapy (SBRT) and fluorouracil or capecitabine with or without zoledronic acid work in treating participants with pancreatic cancer that has spread to nearby tissue or lymph nodes. Hypofractionated stereotactic body radiation therapy is a specialized radiation therapy that sends higher doses of x-rays over a shorter period of time directly to the tumor using smaller doses over several days which may cause less damage to normal tissue. Drugs used in chemotherapy, such as fluorouracil and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Zoledronic acid is used in cancer patients to reduce cancer symptoms and may make tumor cells more sensitive to radiation. Giving hypofractionated stereotactic body radiation therapy and fluorouracil or capecitabine with or without zoledronic acid may work better in treating pancreatic cancer.

Conditions

Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage I Pancreatic Cancer AJCC v6 and v7; Stage IA Pancreatic Cancer AJCC v6 and v7; Stage IB Pancreatic Cancer AJCC v6 and v7; Stage II Pancreatic Cancer AJCC v6 and v7; Stage IIA Pancreatic Cancer AJCC v6 and v7; Stage IIB Pancreatic Cancer AJCC v6 and v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IV Pancreatic Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (3)

• Local control With and Without Zometa at Four Months in Follow-up

  Local control of tumor will be determined by four dimensional (4D) computed tomography (CT) scans and comparison made between participants receiving Zometa and those who don't.

  At 4 months in follow-up

• Local control With and Without Zometa at Eight Months in Follow-up

  Local control of tumor will be determined by four dimensional (4D) computed tomography (CT) scans and comparison made between participants receiving Zometa and those who don't.

  At 8 months in follow-up

• Local control With and Without Zometa at Twelve Months in Follow-up

  Local control of tumor will be determined by four dimensional (4D) computed tomography (CT) scans and comparison made between participants receiving Zometa and those who don't.

  At 12 months in follow-up

Secondary Outcomes (8)

• Maximum Tolerated Dose of Zoledronic Acid

  Up to 30 days after surgery

• Local Failure-free Survival With and Without Zometa

  From date of administration of study drug to the date of local failure, assessed up to 5 years

• Overall Survival With and Without Zometa

  From date of administration of study drug to the date of death, assessed up to 5 years

• Surgically Complete Resection Rate With and Without Zometa

  Immediately after surgery

• Pathologic Response After Resection With and Without Zometa

  Immediately after surgery

Other Outcomes (2)

• RNA Sequence Assessment of Gene Expression of Cholesterol Biosynthesis for Resection With or Without Zometa

  Up to 5 years

• Pharmacokinetics of Zoledronic Acid

  At 0 and 1 hours post-zoledronic acid dose, and before stereotactic body radiation therapy (SBRT) treatments on days 2, 3, 4, and 5

Study Arms (2)

Arm A (chemotherapy, radiation therapy)

ACTIVE COMPARATOR

Participants undergo hypofractionated stereotactic body radiation therapy in 5 fractions on days 1-5. Participants receive fluorouracil IV over 24 hours on day 1 weekly for 4 weeks or capecitabine by mouth every 12 hours starting the evening before day 1 of radiation therapy for 4 weeks as per standard of care. Participants then undergo surgery 6-8 weeks after completion of radiation therapy.

Drug: Capecitabine; Drug: Fluorouracil; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Radiation: Stereotactic Body Radiation Therapy

Arm B (zoledronic acid, chemotherapy, radiation therapy)

EXPERIMENTAL

Participants receive zoledronic acid IV over a minimum of 15 minutes 1 week prior to radiation therapy. Participants undergo hypofractionated stereotactic body radiation therapy and receive treatment with fluorouracil IV or capecitabine by mouth as in Arm A. Participants then undergo surgery 6-8 weeks after completion of radiation therapy.

Drug: Capecitabine; Drug: Fluorouracil; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Radiation: Stereotactic Body Radiation Therapy; Drug: Zoledronic Acid

Interventions

Capecitabine DRUG

Given by mouth (PO)

Also known as: Ro 09-1978/000, Xeloda

Arm A (chemotherapy, radiation therapy); Arm B (zoledronic acid, chemotherapy, radiation therapy)

Fluorouracil DRUG

Given Intravenously (IV)

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Arm A (chemotherapy, radiation therapy); Arm B (zoledronic acid, chemotherapy, radiation therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (chemotherapy, radiation therapy); Arm B (zoledronic acid, chemotherapy, radiation therapy)

Pharmacological Study OTHER

Correlative studies

Arm A (chemotherapy, radiation therapy); Arm B (zoledronic acid, chemotherapy, radiation therapy)

Stereotactic Body Radiation Therapy RADIATION

Undergo hypofractionated stereotactic radiotherapy

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Arm A (chemotherapy, radiation therapy); Arm B (zoledronic acid, chemotherapy, radiation therapy)

Zoledronic Acid DRUG

Given IV

Also known as: [1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bisphosphonic Acid, CGP 42446, CGP42446A, NDC-Zoledronate, Reclast, ZOL 446, Zometa

Arm B (zoledronic acid, chemotherapy, radiation therapy)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed pancreatic adenocarcinoma, either initially diagnosed or recurrent locally advanced disease. The maximum dimension of the treatment target must be =\<10 cm. Locally advanced disease defined as: T 1-2N+MO or T3-4 NxMo, or borderline resectable and unresectable adenocarcinoma without distant metastatic disease or resectable T3-4 NxMo disease or M1 with controlled distant disease
• Inoperable conditions with resectable disease (T1-2NoMo)
• Karnofsky performance status of 60% or better. Received recent chemotherapy for pancreatic cancer or completed chemotherapy \> 5 years ago for malignancies other than pancreatic cancer with no evidence of the second malignancy at study entry
• Radiation therapy completed \> 5 years ago for malignancies other than pancreatic cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field and no evidence of the second malignancy at study entry
• All malignant disease must be able to be encompassed within a single irradiation field
• Absolute neutrophil count (ANC) greater than or equal to 1500/uL
• Radiographically assessable disease
• Platelet count greater than or equal to 100,000/uL
• Serum creatinine less than or equal to 2.0 mg/dL and total bilirubin less than or equal to 2.0 mg/dL in the absence of biliary obstruction. If biliary obstruction is present, biliary decompression will be required, either endoscopic placement of a biliary stent or percutaneous transhepatic. Once biliary drainage has been established, institution of protocol therapy may proceed when the total bilirubin falls to 4.0 mg/dL or lower
• Calculated creatinine clearance of \>= 35.
• Awareness of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts

You may not qualify if:

• Known allergy to Zometa or to anti-emetics appropriate in conjunction with protocol-directed therapy
• Uncontrolled inter-current illness that might jeopardize the ability of the subject to receive the protocol therapy with reasonable safety. This may include, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia
• Pregnant and nursing women
• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, adequately treated non-invasive carcinomas, or be disease-free for at least 5 years from other cancers
• Active duodenal ulcer or bleeding or history of a gastrointestinal fistula or perforation or other significant bowel problems (severe nausea, vomiting, inflammatory bowel disease and significant bowel resection)
• Known human immunodeficiency virus (HIV) infection, or hepatic insufficiency
• Not currently receiving or have received Zometa within 3 weeks prior to study treatment with Zometa

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Capecitabine; Fluorouracil; dehydroftorafur; Radiosurgery; Zoledronic Acid

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles

Study Officials

• Chi Lin, MD, PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: March 8, 2017
• Study Start: September 16, 2016
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)