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Pre-operative Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma With or Without CCX872-B

2019年7月17日 更新者:Alan Katz

A Phase 1b Trial of Neoadjuvant Stereotactic Body Radiotherapy With or Without CCR2 Inhibitor (CCX872-B) Immunotherapy for Preoperative Treatment of Resectable Pancreatic Cancer

Standard treatment for newly diagnosed operable pancreatic cancer usually involves undergoing surgery first and then receiving chemotherapy with or without radiation therapy. However, the pancreatic cancer often comes back after this treatment. Therefore, the investigators are studying whether giving treatment prior to surgery can help decrease the risk the cancer returns.

Stereotactic Body Radiation Therapy (SBRT) is a highly focused type of radiation therapy commonly used in the treatment of pancreatic cancer. This treatment has been shown to be safe and effective for the preoperative treatment of pancreatic cancer. The purpose of this study is to determine if combining an experimental drug, CCX872-B, with SBRT continues to be safe and whether the combination treatment may be more effective at boosting the participant's immune system's ability to kill the pancreatic cancer.

調査の概要

状態

引きこもった

介入・治療

詳細な説明

The investigators have shown that preoperative SBRT followed by surgical resection is feasible and safe in patients in the previous trial UGIP14107. The investigators have also presented preclinical evidence that inhibiting entry of CCR2+ IM using a small molecule antagonist against CCR2 results in enhanced efficacy of RT 26. The investigators hypothesize that inhibition of the CCR2 axis can potentially up regulate the immune response following radiation, therefore leading to a more robust tumor killing response. In preclinical studies, CCR2 inhibitor has little effect in the absence of RT, therefore, the investigators are not including a drug therapy alone group. To test this hypothesis, a phase Ib clinical trial has been proposed to evaluate the effect of combining stereotactic body radiotherapy with CCR2 inhibition in the neoadjuvant treatment of surgically resectable adenocarcinoma of the head of the pancreas.

The study will consist of two parts in sequential fashion. The first fifteen patients will be assigned to Group 1 and undergo SBRT with CCR2 inhibitor CCX872-B. The primary objective is to establish safety and feasibility of the treatment and analyze biomarkers to determine if combined treatment can stimulate an immune response in human patients. A second group of 5 patients will undergo SBRT alone as a comparison group for biomarker immune response.

The investigators would like to proceed with SBRT and CCX872-B as Group 1 given the investigators already have sufficient data from UGIP14107 to show that SBRT is safe and feasible and studying the combination of SBRT with CCX872-B is the primary scientific objective of this study. If unexpected safety issues occur with Group 1, the investigators would consider closing trial at that time without enrolling any patients in Group 2 which would reduce the number of patients exposed to the study.

研究の種類

介入

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

    • New York
      • Rochester、New York、アメリカ、14642
        • University of Rochester Medical Center

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  1. Patient with pathologically proven diagnosis of adenocarcinoma of the head of the pancreas
  2. CT w/ contrast or MRI of the abdomen and pelvis with contrast within 6 weeks prior to registration
  3. CT chest or PET/CT within 6 weeks prior to registration
  4. Clinically determined to be resectable based on NCCN Criteria 3.2017: No arterial tumor contact (celiac axis, superior mesenteric artery or common hepatic artery) and no tumor contact with the superior mesenteric vein or portal vein, or < 180 degrees contact without vein contour irregularity
  5. No evidence of metastatic disease and/or non-regional lymph node metastases
  6. Adequate cardiopulmonary reserves to tolerate surgery
  7. ECOG performance status 0-2
  8. Adequate bone marrow function defined as follows: White blood cell> 3000cells/mm^3, Absolute neutrophil count (ANC) ≥ 1500 cells/mm3, Platelets ≥ 100,000 cells/mm3, Hemoglobin ≥ 9.0 g/dl
  9. Male or female subjects, aged at least 18 years; Female subjects of childbearing potential may participate if adequate contraception is used during, and for at least the three months after study completion; Male subjects with partners of childbearing potential may participate in the study if they had a vasectomy at least 6 months prior to randomization or if adequate contraception is used during, and for at least the three months after study completion; Adequate contraception is defined as resulting in a failure rate of less than 1% per year
  10. Patient must sign study specific informed consent prior to study entry
  11. Anticipated life expectancy ≥ 12 weeks; -

Exclusion Criteria:

  1. Prior surgical resection of any pancreatic malignancy
  2. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
  3. Any prior systemic or radiation treatment, including investigational treatments, of the patient's pancreatic tumor.
  4. Prior radiotherapy to the region of pancreatic cancer that would result in overlap of radiation therapy fields
  5. Severe, active comorbidity, defined as follows:

    1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    2. Transmural myocardial infarction within the last 6 months
    3. Clinically significant ECG abnormalities e.g. QTcF >450msec
    4. Acute viral, bacterial or fungal infection requiring intravenous antibiotics at the within 4 weeks of registration
    5. Known active HIV, HBV or HCV infections
    6. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration.
    7. Uncontrolled diabetes or hypertension
    8. Serious psychiatric illness or altered mental status
  6. Severe, uncorrectable hepatic insufficiency and/or coagulation defects due to liver failure
  7. Any evidence of distant metastases (M1)
  8. (ONLY applies for Group 1 patients taking CCX872-B )Taking agents known to be strong inhibitors or inducers of CYP3A4 or UGT1A1 within 2 weeks prior to Day 1 dosing; these include atazanavir, boceprevir, clarithromycin, conivaptan, gemfibrozil, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole, rifampin, and carbamazepine; use of these drugs must be avoided during the study and until 2 weeks after stopping CCX872-B treatment -

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

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:非ランダム化
  • 介入モデル:並列代入
  • マスキング:なし(オープンラベル)

武器と介入

参加者グループ / アーム
介入・治療
実験的:Group 1:With CCX872-B
Concurrent SBRT 25 Gy in 5 fractions over 5-7 days, and 21 days of CCX872-B therapy. CCX872-B 150 mg by mouth twice daily approximately 12 hours apart.
CCX872-B concurrent with stereotactic body radiation therapy for pancreatic adenocarcinoma.
介入なし:Group 2:Without CCX872-B
SBRT Alone: 25 Gy in 5 fractions over 5-7 days

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Percentage of patients who complete radiation therapy, drug treatment and surgery
時間枠:6 weeks
Number of patients who proceed through radiation and drug treatment and undergo surgical resection in a timely manner.
6 weeks
Percentage of patients who are ineligible for surgical resection due to toxicity from SBRT + CCX872-B or SBRT alone
時間枠:12 weeks

Assessment of whether patients are made ineligible for surgical resection solely due to toxicities from SBRT + CCX872-B or SBRT alone.

Measure of Grade 3 toxicity directly attributable to SBRT+ CCX872-B or SBRT alone.

Analyze rate of grade 2 or greater acute toxicity caused by SBRT with or without CCX872-B.

Determination of intraoperative and postoperative surgical morbidity following neoadjuvant treatment including the amount of fibrosis and total operative time.

12 weeks

二次結果の測定

結果測定
メジャーの説明
時間枠
Number of participants with no further growth of cancer at original site
時間枠:2 years
Count subjects with no further growth of cancer at original site
2 years
Number of subjects with recurrence of cancer in other body sites
時間枠:2 years
Compare recurrence locations (metastases to other organs or non-regional adenopathy) of treated patients relative to historical controls
2 years
Mean time to progression of pancreatic cancer
時間枠:4 years
Duration of progression free survival of treated patients
4 years
Mean time to death
時間枠:4 years
Measure duration of survival of treated patients
4 years

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (予想される)

2019年8月1日

一次修了 (予想される)

2019年8月31日

研究の完了 (予想される)

2019年8月31日

試験登録日

最初に提出

2018年12月15日

QC基準を満たした最初の提出物

2018年12月15日

最初の投稿 (実際)

2018年12月19日

学習記録の更新

投稿された最後の更新 (実際)

2019年7月19日

QC基準を満たした最後の更新が送信されました

2019年7月17日

最終確認日

2019年7月1日

詳しくは

本研究に関する用語

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?

いいえ

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

はい

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

膵臓がんの臨床試験

  • Jonsson Comprehensive Cancer Center
    National Cancer Institute (NCI); Highlight Therapeutics
    積極的、募集していない
    平滑筋肉腫 | 悪性末梢神経鞘腫瘍 | 滑膜肉腫 | 未分化多形肉腫 | 骨の未分化高悪性度多形肉腫 | 粘液線維肉腫 | II期の体幹および四肢の軟部肉腫 AJCC v8 | III期の体幹および四肢の軟部肉腫 AJCC v8 | IIIA 期の体幹および四肢の軟部肉腫 AJCC v8 | IIIB 期の体幹および四肢の軟部肉腫 AJCC v8 | 切除可能な軟部肉腫 | 多形性横紋筋肉腫 | 切除可能な脱分化型脂肪肉腫 | 切除可能な未分化多形肉腫 | 軟部組織線維肉腫 | 紡錘細胞肉腫 | ステージ I 後腹膜肉腫 AJCC (American Joint Committee on Cancer) v8 | 体幹および四肢の I 期軟部肉腫 AJCC v8 | ステージ... およびその他の条件
    アメリカ

CCX872-Bの臨床試験

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