Gehypofractioneerde stereotactische lichaamsbestralingstherapie en fluorouracil of capecitabine met of zonder zoledroninezuur bij de behandeling van patiënten met lokaal gevorderde alvleesklierkanker
Een gerandomiseerde fase II-studie naar de werkzaamheid en veiligheid van gehypofractioneerde stereotactische radiotherapie en 5FU of capecitabine met en zonder zometa bij patiënten met lokaal gevorderd pancreasadenocarcinoom
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.
Studie Overzicht
Toestand
Conditie
- Pancreas Adenocarcinoom
- Recidiverend pancreascarcinoom
- Stadium III Alvleesklierkanker AJCC v6 en v7
- Stadium IV alvleesklierkanker AJCC v6 en v7
- Stadium I alvleesklierkanker AJCC v6 en v7
- Stadium IA Alvleesklierkanker AJCC v6 en v7
- Stadium IB Alvleesklierkanker AJCC v6 en v7
- Stadium II alvleesklierkanker AJCC v6 en v7
- Stadium IIA alvleesklierkanker AJCC v6 en v7
- Stadium IIB pancreaskanker AJCC v6 en v7
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Nebraska
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Omaha, Nebraska, Verenigde Staten, 68198
- University of Nebraska Medical Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: 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)
Andere namen:
Given Intravenously (IV)
Andere namen:
Undergo hypofractionated stereotactic radiotherapy
Andere namen:
|
|
Experimenteel: 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)
Andere namen:
Given Intravenously (IV)
Andere namen:
Undergo hypofractionated stereotactic radiotherapy
Andere namen:
Given IV
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Local Control With and Without Zometa at Four Months in Follow-up
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Grade 3 and Above Adverse Events With and Without Zoledronic Acid
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Immediately after surgery
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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
|
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Pathologic Response After Resection With and Without Zometa
Tijdsspanne: 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
|
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All-Cause Mortality
Tijdsspanne: 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
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Chi Lin, MD, PhD, University of Nebraska
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Endocriene systeemziekten
- Neoplasmata per site
- Neoplasmata
- Neoplasmata van het spijsverteringsstelsel
- Ziekten van het spijsverteringsstelsel
- Endocriene klierneoplasmata
- Alvleesklier Ziekten
- Pancreasneoplasmata
- Organische chemicaliën
- Heterocyclische verbindingen, 1-ring
- Heterocyclische verbindingen
- Onderzoekstechnieken
- Therapeutica
- Chirurgische procedures, operatief
- Azoles
- Nucleïnezuren, nucleotiden en nucleosiden
- Imidazolen
- Deoxycytidine
- Cytidine
- Pyrimidine -nucleosiden
- Pyrimidines
- Organofosforverbindingen
- Nucleosiden
- Uracil
- Pyrimidinonen
- Radiotherapie
- Stereotaxische technieken
- Neurochirurgische procedures
- Deoxyribonucleosides
- Organofosfonaten
- Difosfonaten
- Capecitabine
- Zoledroninezuur
- Fluorouracil
- Radiochirurgie
- Dehydroforafur
Andere studie-ID-nummers
- 0552-16-FB
- P30CA036727 (Subsidie/contract van de Amerikaanse NIH)
- NCI-2016-01360 (Register-ID: CTRP (Clinical Trial Reporting Program))
Plan Individuele Deelnemersgegevens (IPD)
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