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Hypofraktioneret stereootaktisk kropsstrålebehandling og fluorouracil eller capecitabin med eller uden zoledronsyre til behandling af patienter med lokalt fremskreden kræft i bugspytkirtlen

2. november 2026 opdateret af: University of Nebraska

Et randomiseret fase II-studie af effektiviteten og sikkerheden af ​​hypofraktioneret stereootaktisk strålebehandling og 5FU eller Capecitabin med og uden Zometa hos patienter med lokalt avanceret pancreasadenokarcinom

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.

Studieoversigt

Status

Aktiv, ikke rekrutterende

Intervention / Behandling

Detaljeret beskrivelse

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.

The primary study objective is to evaluate the efficacy of hypofractionated radiation therapy concurrently with zoledronic acid (Zometa) and fluorouracil or capecitabine. Other study objectives include examining the toxicity of Zometa when used concurrently with hypofractionated radiation therapy, evaluating local failure-free survival and overall survival, determining surgical resection and tumor response rates, measuring Zometa pharmacokinetics, evaluating tumor and organ motion and determining the effect those on the dosimetry, local control and survival. Post-treatment follow-up is for 30 days, then every 3 months for the first year, every 4 months for the second year, and every 6 months thereafter.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

46

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Nebraska
      • Omaha, Nebraska, Forenede Stater, 68198
        • University of Nebraska Medical Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

19 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Arm A (chemotherapy, radiation therapy)

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.

Correlative studies

Correlative studies

Given by mouth (PO)

Andre navne:
  • Xeloda
  • Ro 09-1978/000

Given Intravenously (IV)

Andre navne:
  • 5-FU
  • 5-Fluracil
  • Fluracil
  • 5-fluor-2,4(1H,3H)-pyrimidindion
  • 5-Fluorouracil
  • AccuSite
  • Carac
  • Fluor Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Undergo hypofractionated stereotactic radiotherapy

Andre navne:
  • SBRT
  • SABR
  • Stereotaktisk ablativ kropsstrålingsterapi
Eksperimentel: Arm B (zoledronic acid, chemotherapy, radiation therapy)

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.

Correlative studies

Correlative studies

Given by mouth (PO)

Andre navne:
  • Xeloda
  • Ro 09-1978/000

Given Intravenously (IV)

Andre navne:
  • 5-FU
  • 5-Fluracil
  • Fluracil
  • 5-fluor-2,4(1H,3H)-pyrimidindion
  • 5-Fluorouracil
  • AccuSite
  • Carac
  • Fluor Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Undergo hypofractionated stereotactic radiotherapy

Andre navne:
  • SBRT
  • SABR
  • Stereotaktisk ablativ kropsstrålingsterapi

Given IV

Andre navne:
  • Genlast
  • Zometa
  • CGP 42446
  • CGP42446A
  • [1-Hydroxy-2-(1H-imidazol-1-yl)ethyliden]bisphosphonsyre
  • NDC-Zoledronat
  • ZOL 446

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Local Control With and Without Zometa at Four Months in Follow-up
Tidsramme: At 4 months in follow-up

Local control will be assessed using three-dimensional (3D) computed tomography (CT). The primary tumor will be contoured using Varian planning software, and tumor volume will be measured at baseline and at 4 months post-treatment. Local control is defined as absence of disease progression, with progression defined as a ≥25% increase in tumor volume. Tumor response will also be assessed using RECIST-based criteria (≥20% increase in tumor diameter) as a supportive analysis.

At 4 months in follow-up
Local Control With and Without Zometa at Eight Months in Follow-up
Tidsramme: At 8 months in follow-up

Local control will be assessed using three-dimensional (3D) computed tomography (CT). The primary tumor will be contoured using Varian planning software, and tumor volume will be measured at baseline and at 8 months post-treatment. Local control is defined as absence of disease progression, with progression defined as a ≥25% increase in tumor volume. Tumor response will also be assessed using RECIST-based criteria (≥20% increase in tumor diameter) as a supportive analysis.

At 8 months in follow-up
Local Control With and Without Zometa at Twelve Months in Follow-up
Tidsramme: At 12 months in follow-up

Local control will be assessed using three-dimensional (3D) computed tomography (CT). The primary tumor will be contoured using Varian planning software, and tumor volume will be measured at baseline and at 12 months post-treatment. Local control is defined as absence of disease progression, with progression defined as a ≥25% increase in tumor volume. Tumor response will also be assessed using RECIST-based criteria (≥20% increase in tumor diameter) as a supportive analysis.

At 12 months in follow-up

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Grade 3 and Above Adverse Events With and Without Zoledronic Acid
Tidsramme: Up to 30 days after treatment

Grade 3 and above adverse events (AE) will be determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Up to 30 days after treatment
Failure-free Survival With and Without Zometa
Tidsramme: From date of administration of study drug to the date of any failure, assessed up to 5 years

Time to any failure (disease progression or recurrence determined by imaging, or death) will be analyzed using Kaplan-Meier method between participants receiving Zometa and those who don't.

From date of administration of study drug to the date of any failure, assessed up to 5 years
Overall Survival With and Without Zometa
Tidsramme: From date of administration of study drug to the date of death, assessed up to 5 years

Time to death will be analyzed using Kaplan-Meier method between participants receiving Zometa and those who don't.

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
Tidsramme: Immediately after surgery

The number and proportion of participants undergoing complete resection (negative margin) will be determined between participants receiving Zometa and those who don't.

Immediately after surgery
Pathologic Response After Resection With and Without Zometa
Tidsramme: Immediately after surgery

The pathologic response will be scored from 0-9 by a pathologist, 0 is no response and 9 is complete response between participants receiving Zometa and those who don't.

Immediately after surgery
All-Cause Mortality
Tidsramme: From date of administration of study drug to the date of death, assessed up to 10 years

All anticipated and unanticipated deaths due to any cause

From date of administration of study drug to the date of death, assessed up to 10 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Samarbejdspartnere

Efterforskere

  • Ledende efterforsker: Chi Lin, MD, PhD, University of Nebraska

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

23. marts 2017

Primær færdiggørelse (Faktiske)

12. december 2023

Studieafslutning (Anslået)

1. december 2027

Datoer for studieregistrering

Først indsendt

28. februar 2017

Først indsendt, der opfyldte QC-kriterier

2. marts 2017

Først opslået (Faktiske)

8. marts 2017

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

4. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

2. november 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • 0552-16-FB
  • P30CA036727 (U.S. NIH-bevilling/kontrakt)
  • NCI-2016-01360 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for individuelle deltagerdata (IPD)

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