局所進行膵臓がん患者の治療におけるゾレドロン酸併用または非併用の低分割定位放射線療法およびフルオロウラシルまたはカペシタビン
局所進行膵臓腺癌患者におけるゾメタの有無にかかわらず、少分割定位放射線療法および 5FU またはカペシタビンの有効性と安全性に関する無作為化第 II 相試験
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.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
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.
研究の種類
研究の種類
入学 (実際)
入学
段階
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Nebraska
-
Omaha、Nebraska、アメリカ、68198
- University of Nebraska Medical Center
-
-
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
アクティブコンパレータ：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)
他の名前：
Given Intravenously (IV)
他の名前：
Undergo hypofractionated stereotactic radiotherapy
他の名前：
|
|
実験的：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)
他の名前：
Given Intravenously (IV)
他の名前：
Undergo hypofractionated stereotactic radiotherapy
他の名前：
Given IV
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Local Control With and Without Zometa at Four Months in Follow-up
時間枠：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
時間枠：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
時間枠：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
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Grade 3 and Above Adverse Events With and Without Zoledronic Acid
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
協力者
協力者
捜査官
捜査官
- 主任研究者：Chi Lin, MD, PhD、University of Nebraska
研究記録日
主要日程の研究
研究開始 (実際)
研究開始
一次修了 (実際)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- 0552-16-FB
- P30CA036727 (米国 NIH グラント/契約)
- NCI-2016-01360 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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