不一致修復の手術後の再発を防ぐための免疫療法（トーパリマブ）IIB、IIC、またはIII結腸癌のステージ不足
ミスマッチ修復不足を伴う高リスクの局所的な結腸癌における補助トリパリマブの第II相試験
This phase II trial tests how well immunotherapy (toripalimab) works for reducing the risk of cancer recurrence after surgery in patients with mismatch repair deficient stage IIB, IIC, or III colon cancer.
調査の概要
状態
詳細な説明
PRIMARY OBJECTIVE:
I. Evaluate the efficacy of adjuvant toripalimab in patients with resected stage IIB, IIC, and III mismatch repair deficient (dMMR) colon cancer by measuring 3-year disease-free survival.
SECONDARY OBJECTIVES:
I. Define the immune related toxicity profile of toripalimab in the adjuvant setting.
II. Further evaluate the efficacy of adjuvant toripalimab specifically by measuring 3-year relapse free survival (RFS), 5-year disease free survival (DFS), and 5-year overall survival.
TERTIARY/EXPLORATORY OBJECTIVES:
I. To explore immune, ctDNA, and omic markers associated with clinical efficacy (DFS).
II. To assess patient reported outcomes (PRO) and health related quality of life (QoL).
OUTLINE:
Eligible consenting participants will receive toripalimab intravenously every 3 weeks for 6 months (8 doses) in the absence of disease recurrence or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months until 5 years post-resection. After completion of study medication, participants undergo surveillance follow up with blood tests, computed tomography (CT) scans, colonoscopy at specified intervals until 5 years post-resection. Patient reported outcomes and quality of life will also be assessed with questionnaires.
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：Oluwadunni E. Emiloju, MBBS, MS
- 電話番号：404-778-1900
- メール：oluwadunni.eunice.emiloju@emory.edu
研究連絡先のバックアップ
- 名前：Olatunji B. Alese, MD, FASCO
- メール：olatunji.alese@emory.edu
研究場所
-
-
Georgia
-
Atlanta、Georgia、アメリカ、30322
- 募集
- Emory University Hospital/Winship Cancer Institute
-
主任研究者：
- Oluwadunni E. Emiloju, MBBS, MS
-
コンタクト：
- Tyler Whitfield
- 電話番号：404-778-1900
- メール：tyler.stephen.whitfield@emory.edu
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Atlanta、Georgia、アメリカ、30308
- 募集
- Emory University Hospital Midtown
-
コンタクト：
- Jalpa Patel
- メール：jalpa.r.patel@emory.edu
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主任研究者：
- Oluwadunni E. Emiloju, MBBS, MS
-
Atlanta、Georgia、アメリカ、30342
- 募集
- Emory Saint Joseph's Hospital
-
主任研究者：
- Oluwadunni E. Emiloju, MBBS, MS
-
コンタクト：
- Ainsley Hymel
- メール：ainsley.hymel@emory.edu
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Atlanta、Georgia、アメリカ、30033
- 募集
- Emory Decatur Hospital
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主任研究者：
- Oluwadunni Emiloju
-
コンタクト：
- Kathleen Coleman
- 電話番号：404-778-1900
- メール：kmcole5@emory.edu
-
Johns Creek、Georgia、アメリカ、30097
- 募集
- Emory Johns Creek Hospital
-
主任研究者：
- Oluwadunni E. Emiloju, MBBS, MS
-
コンタクト：
- Hafsa Ahmed
- メール：hafsa.maheen.ahmed@emory.edu
-
-
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 resected pathologic stage IIB, IIC and III dMMR colon cancer (American Joint Committee on Cancer [AJCC] 8)
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Deficient mismatch repair (MMR) by immunohistochemistry or microsatellite instability (MSI-H) by polymerase chain reaction (PCR) or next generation sequencing (NGS)
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Complete (R0) resection of pathologic stage IIB, IIC and III dMMR colon cancer 4 to 12 weeks prior to first dose of study drug
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Available tissue sample from surgical specimen
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Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
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Absolute neutrophil count (ANC) ≥ 1,000 /mcL
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Platelets ≥ 75,000 / mcL
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Hemoglobin ≥ 9 g/dL or ≥ 5.0 mmol/L
- Transfusion is allowed to obtain an adequate hemoglobin level
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Creatinine ≤ 1.5 x upper limit of normal (ULN) or measured or calculated creatinine clearance ≥ 40 mL/min for patient with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
- Creatinine clearance should be calculated per institutional standard
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Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN
- Patients with previously diagnosed Gilbert syndrome can have total bilirubin < 3.0 mg/dL
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Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x ULN
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Alkaline phosphatase ≤ 3 x ULN
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Signed informed consent
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Patients at least 18 years of age
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Colonoscopy should be performed before surgery and if synchronous colon cancers are present, both must have deficient MMR and both must have undergone complete resection for patient to be eligible. If colonoscopy was not done pre-operatively, the patient may still be eligible if all other inclusion criteria are met. It should however be performed within 6 months after initial colon resection surgery
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Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. WOCBP are women younger than 55 years (yrs) of age excluding those who are surgically unable to get pregnant due to prior hysterectomy and or bilateral salpingo-oophorectomy
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Patients of childbearing / reproductive potential should use adequate birth control methods, as defined by the investigator, during the study treatment period and for a period of 90 days after the last dose of study drug. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard
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Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 90 days after the last dose of study drug
Exclusion Criteria:
- Neoadjuvant treatment for dMMR colon cancer
- Presence of metastatic dMMR colon cancer
- Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of adverse events
- Uncontrolled psychiatric illness or psychological condition potentially hampering compliance with the study protocol and follow-up schedule
- History of pneumonitis requiring treatment with steroids, or history of interstitial lung disease
- History of prior malignancy other than the cancer under study, that is progressing or has required active treatment within the past 3 years. Exceptions include adequately treated basal cell or squamous cell carcinoma of skin, superficial bladder cancer, in situ cervical cancer, in situ breast cancer, other in situ cancers, prostate cancer with a Gleason score ≤6 that does not need therapy or other local tumors that are considered cured.
- Autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo, diabetes mellitus type 1, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, controlled psoriasis or resolved childhood asthma/atopy not requiring systemic treatment can be enrolled
- Active hepatitis B or hepatitis C
- Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Treatment with live vaccines within 30 days prior to the first dose of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, nasal seasonal flu, H1N1 flu, rabies, Bacille Calmette Guerin (BCG) and typhoid vaccine
- Prior treatment with any immune checkpoint inhibitor
- Current pregnancy or breastfeeding
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：なし
- 介入モデル：単一グループの割り当て
- 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：Treatment (toripalimab)
Eligible consenting participants receive toripalimab intravenously every 3 weeks for 6 months (8 doses) in the absence of disease recurrence or unacceptable toxicity. Following this, patients undergo surveillance follow up with blood tests, computed tomography (CT) scans, colonoscopy at specified intervals until 5 years post-resection. For patients who have a recurrence, a biopsy will be performed at the time of recurrence. |
Undergo CT
他の名前：
Ancillary studies Undergo biopsy
他の名前：
Undergo collection of blood samples
他の名前：
Undergo colonoscopy 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
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
3-year Disease free survival (DFS)
時間枠：Time between the date of registration and the first date of documented recurrence or death due to any cause assessed up to 3 years
|
Time between the date of registration and the first date of documented recurrence, regardless of discontinuation of study drug, or death due to any cause, assessed at 3 years |
Time between the date of registration and the first date of documented recurrence or death due to any cause assessed up to 3 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of treatment-related adverse events
時間枠：Up to 5 years
|
Safety will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Treatment-related adverse events (defined as potentially, probably and definitely) will be summarized in preferred term by system organ class and listed on an individual subject basis at patient level. Immune-related adverse events will also be tabulated. |
Up to 5 years
|
|
3-year Relapse free survival (RFS)
時間枠：Time between the date of registration and the first date of documented disease recurrence assessed up to 3 years.
|
Time between the date of registration and the first date of documented disease recurrence, assessed at 3 years |
Time between the date of registration and the first date of documented disease recurrence assessed up to 3 years.
|
|
5-year DFS
時間枠：Time between the date of registration and the first date of documented recurrence, or death due to any cause assessed up to 5 years
|
Time between the date of registration and the first date of documented recurrence, regardless of discontinuation of study drug, or death due to any cause, assessed at 5 years. |
Time between the date of registration and the first date of documented recurrence, or death due to any cause assessed up to 5 years
|
|
Colon cancer specific survival (CCSC)
時間枠：Time between the date of registration and the date of death due to colon cancer, assessed up to 5 years
|
CCSC is the time between the date of registration and the date of death due to colon cancer, assessed up to 5 years |
Time between the date of registration and the date of death due to colon cancer, assessed up to 5 years
|
|
Overall survival (OS)
時間枠：Time between the date of registration and the date of death due to any cause, assessed up to 5 years
|
Time between the date of registration and the date of death due to any cause. |
Time between the date of registration and the date of death due to any cause, assessed up to 5 years
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Oluwadunni E. Emiloju, MBBS, MS、Emory University Hospital/Winship Cancer Institute
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
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
- STUDY00008833
- P30CA138292 (米国 NIH グラント/契約)
- STUDY00008833 (その他の識別子：Emory University Hospital/Winship Cancer Institute)
- NCI-2025-05423 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- WINSHIP6483-24 (その他の識別子：Emory University Hospital/Winship Cancer Institute)
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
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