BMX-001を併用した/併用しない短期および長期コース放射線治療の有効性と安全性の試験
新たに局所進行性直腸腺癌と診断された患者における総術前補助療法の一部として、BMX-001を併用する場合と併用しない場合の短期および長期コースの放射線療法の有効性と安全性に関する無作為化第2相試験
In this Phase 2 study, we will conduct an efficacy and safety study of the combination of investigational drug BMX-001, with short-course radiotherapy (SCRT) or long-course chemoradiotherapy (LCCRT) as part of total neoadjuvant therapy in newly diagnosed rectal adenocarcinoma (RAC) patients.
調査の概要
詳細な説明
In this trial, we will enroll patients in two cohorts:
Cohort 1: A 6 patient safety lead-in for patients receiving capecitabine prior to beginning a randomized trial for the Long Course Chemo-radiation (LCCRT) cohort. There will be trial stopping rules to review safety and PK data prior to initiating the randomized trial of patients receiving LCCRT.
Cohort 2: The Randomized Short Course Radiation (SCRT) cohort.
Cohort 1 and 2 will begin enrolling concurrently. Cohort 1 will have a safety lead-in of patients receiving LCCRT (with capecitabine). Cohort 2 will begin with the randomized study of patients receiving SCRT, while the LCCRT cohort is going through the safety lead-in portion.
There are stopping rules for the LCCRT cohort 1 pending PK analysis as well as an AE review from the treatment period plus 1 week post BMX-001 treatment for the 6 patients prior to moving on with the randomized portion of the study for the LCCRT cohort. All patients in the safety lead-in portion of the trial will receive BMX-001 (A loading dose of 28 mg/subject followed by maintenance doses of 14 mg/subject twice a week) with either SCRT or LCCRT. Patients will receive 3 cycles of FOLFOX or 2 cycles of CAPOX and then be assigned to SCRT or LCCRT prior to randomization. Patients will be randomized (stratified by gender) to BMX-001 or no BMX-001. The randomized trial in each cohort will involve SCRT or LCCRT with or without BMX-001. After conclusion of radiation, patients will then receive 6 more cycles of FOLFOX or 4 more cycles of CAPOX. Skin, GI, and GU symptoms will be measured on the day of screening, before and after RT.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：IIT Office
- 電話番号：402-559-4596
- メール：IITOffice@unmc.edu
研究場所
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Kentucky
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Lexington、Kentucky、アメリカ、40536
- 募集
- Markey Cancer Center
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コンタクト：
- Samantha F Stokely, BSN, RN
- 電話番号：859-323-4128
- メール：samantha.stokley1@uky.edu
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コンタクト：
- Cynthia A Leedham, Ph.D
- 電話番号：859-257-4470
- メール：cleed2@uky.edu
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主任研究者：
- Mark E Bernard, MD
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Nebraska
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Omaha、Nebraska、アメリカ、68198
- 募集
- University of Nebraska Medical Center
-
主任研究者：
- Chi Lin, MD, Ph.D
-
コンタクト：
- IIT Office
- 電話番号：402-559-4596
- メール：IITOffice@unmc.edu
-
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Texas
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San Antonio、Texas、アメリカ、78229
- 募集
- UT Health San Antonio MD Anderson Cancer Center
-
コンタクト：
- Vanessa N Collazo Velez, RN, MS
- 電話番号：210-450-7382
- メール：collazovelez@uthscsa.edu
-
コンタクト：
- James J Denno
- 電話番号：210-450-5887
- メール：dennoj@uthscsa.edu
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主任研究者：
- Neil B Newman, MD
-
-
参加基準
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:
- Patients with pathologically confirmed locally advanced rectal adenocarcinoma who will be receiving total neoadjuvant therapy regimen with curative intent.
- AJCC stage II to III rectal adenocarcinoma that will require total neoadjuvant therapy.
- Adult, age > or equal to 18 years (for Nebraska, age of consent is ≥19 years old)
- ECOG Performance Status 0-2
- Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 /dl, platelets ≥ 100,000 /dl (The use of transfusion or other intervention to achieve Hgb > 9.0 g/dl is acceptable)
- Serum SGOT and bilirubin ≤ 1.5 times upper limit of normal
- Adequate renal function defined as follows:
1)Serum creatinine < 1.5 mg/dl within 2 weeks prior to enrollment or 2)Creatinine clearance (CC) ≥ 50 ml/min within 2 weeks prior to enrollment determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)], CCr female = 0.85 x (CrCl male) 8. Signed, written informed consent prior to completing any study specific procedures 9. Negative pregnancy test for women of child-bearing potential at the time of screening 10. Women of childbearing potential and male participants must agree to use two forms of a medically effective means of birth control throughout their participation in the treatment phase of the study and until 12 months following the last study treatment 11. Chest/Abdominal/Pelvic (CAP) CT/ pelvic MRI done within 8 weeks prior to randomization.
Exclusion Criteria:
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Breast-feeding or pregnant
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Active infection requiring IV antibiotics 7 days before enrollment
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Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ, basal cell or carcinoma of the skin, invasive cancers with a 5-year disease-free interval, resected cancer of the bladder or low-grade (Gleason 6 or less) prostate cancer
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Prior history of rectal adenocarcinoma (RAC)
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Prior history of pelvic radiotherapy for any other type of malignancy
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Known hypersensitivity or contraindication to any agent in FOLFOX or CAPOX regimen.
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Because corticosteroids are anti-inflammatory and could interrupt oxidative stress, patients will be excluded unless they are on stable or decreasing corticosteroids dose at the time of randomization.
BMX-001 Specific Exclusion Criteria (Subjects meeting any of the following criteria are ineligible for study entry)
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Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
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Active or history of postural hypotension and autonomic dysfunction within the past year
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Known hypersensitivity to BMX-001
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Clinically significant (i.e. active) cardiovascular disease or cerebrovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
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History or evidence upon physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication or potentially interfering with protocol treatment
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Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment
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A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms) (CTCAE grade 1) using the specific/usual choice by clinical center for correction factor.
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A history of additional risk factors for Torsades de Pointes (TdP) (e.g., congestive heart failure, hypokalemia, known family history of Long QT Syndrome).
Note: Inclusion of Women and Minorities Both men and women and members of all races and ethnic groups are eligible for this trial.
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：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Arm A
Short Chemo-Radiation Therapy (SCRT) + BMX-001 |
Loading dose of 28 mg per subject, followed by maintenance doses of 14 mg per subject twice per week. |
|
介入なし：Arm B
Short Chemo-Radiation Therapy (SCRT) |
|
|
実験的：Arm C
Long Course Chemo-Radiation Therapy (LCCRT) + BMX-001 |
Loading dose of 28 mg per subject, followed by maintenance doses of 14 mg per subject twice per week. |
|
介入なし：Arm D
Long Course Chemo-Radiation Therapy (LCCRT) |
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 |
|---|---|---|
|
Efficacy of BMX-001 as measured by Grade 3 and above associated with gastrointestinal Toxicities
時間枠：Three weeks (During and 2 weeks after RT)
|
Grade 3 and above radiation-associated gastrointestinal, genitourinary, skin and hematologic toxicity (SCRT or LCCRT) including frequency, severity and duration of rectal bleeding, rectal pain, diarrhea, dysuria, hematuria, urinary frequency, radiation dermatitis and thrombocytopenia |
Three weeks (During and 2 weeks after RT)
|
|
Efficacy of BMX-001 as measured by Grade 3 and above associated with genitourinary Toxicities
時間枠：Three weeks (During and 2 weeks after RT)
|
Grade 3 and above radiation-associated gastrointestinal, genitourinary, skin and hematologic toxicity (SCRT or LCCRT) including frequency, severity and duration of rectal bleeding, rectal pain, diarrhea, dysuria, hematuria, urinary frequency, radiation dermatitis and thrombocytopenia |
Three weeks (During and 2 weeks after RT)
|
|
Efficacy of BMX-001 as measured by Grade 3 and above associated with skin Toxicities
時間枠：Three weeks (During and 2 weeks after RT)
|
Grade 3 and above radiation-associated gastrointestinal, genitourinary, skin and hematologic toxicity (SCRT or LCCRT) including frequency, severity and duration of rectal bleeding, rectal pain, diarrhea, dysuria, hematuria, urinary frequency, radiation dermatitis and thrombocytopenia |
Three weeks (During and 2 weeks after RT)
|
|
Efficacy of BMX-001 as measured by Grade 3 and above associated with hematologic Toxicities
時間枠：Three weeks (During and 2 weeks after RT)
|
Grade 3 and above radiation-associated gastrointestinal, genitourinary, skin and hematologic toxicity (SCRT or LCCRT) including frequency, severity and duration of rectal bleeding, rectal pain, diarrhea, dysuria, hematuria, urinary frequency, radiation dermatitis and thrombocytopenia |
Three weeks (During and 2 weeks after RT)
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Chi Lin, MD, PhD、University of Nebraska
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
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
詳しくは
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