切除不能な結腸直腸癌肝転移に対する生体肝移植
結腸直腸癌からの切除不能な肝転移に対するネオアジュバント化学療法と生体ドナー肝移植の組み合わせを使用したプロトコルの評価
Patients with unresectable liver metastases (LM) from colorectal cancer (CRC)have a poor prognosis. In patients with resectable disease, surgery offers a distinct survival benefit. This study will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing) on standard chemotherapy. Potential participants will be evaluated for liver transplant suitability and must also have a willing, healthy living donor come forward for evaluation. Those participants who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a "control group" of participants who drop out of study prior to transplantation due to reasons other than cancer progression.
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
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Approximately half of all patients develop metastases, often to the liver or lung. Surgical treatment of liver metastases (LM) is the only curative treatment option; however, it has been estimated that only 20-40% of patients are candidates for liver resection. Surgery offers a distinct survival advantage: the 5-year survival after liver resection for LM is around 40-50% in most studies versus 10-20% 5-year survival for chemotherapy alone.
In cases where the colorectal metastases are isolated to the liver but "unresectable", the total hepatectomy resulting from liver transplantation would remove all evident disease. CRC LM are considered an absolute contraindication for liver transplantation (LT) at most centers but recent reports of LT for colorectal LM from a single center in Oslo, Norway demonstrated a 5-year survival of 56%. The Norway study was not stringent about inclusion criteria or pre-transplant chemotherapy, and transplanted patients whose tumors were actively growing. As a result many participants developed disease recurrence quite rapidly following transplant. The investigators hypothesize that tighter criteria would result in improved outcomes.
Unfortunately, with a lack of deceased donor grafts for the investigators existing transplant patients, the investigators cannot utilize decease donor grafts for this study. Therefore the investigators will explore Living Donor Liver Transplantation (LDLT). Furthermore, LDLT is an elective surgery, allowing for more control over pre-transplant chemotherapy and tumor monitoring. This study will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing) on standard chemotherapy. Potential participants will be evaluated for liver transplant suitability and must also have a willing, healthy living donor come forward for evaluation. Those participants who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a "control group" of participants who drop out of study prior to transplantation due to reasons other than cancer progression.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- 適用できない
連絡先と場所
研究場所
-
-
Ontario
-
Toronto、Ontario、カナダ、M5G 2N2
- Toronto General Hospital
-
-
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:
- Must reside in Canada
- ECOG ( Eastern Cooperative Oncology Group) score : 0-1 at all times prior to LDLT (excursions to ECOG 2 allowed at investigator's discretion)
- Proven colorectal Liver Metastases (LM).
- Willing and able to provide written informed consent.
- Negative serum pregnancy test for women of childbearing potential
- Both men and women must agree to use adequate barrier birth control measures during the course of the trial.
- At least 1 "acceptable", ABO-compatible living donor has stepped forward
- Primary Colorectal cancer tumor stage is ≤T4a
- Time from primary CRC resection to transplant is ≥6 months
- Bilateral and non-resectable LM
- No major vascular invasion by LM; metastases isolated to liver
- The patient has undergone systemic chemotherapy (eg. FOLFOX +/- bevacizumab or FOLFIRI +/- bevacizumab) for ≥3 months
- demonstrated stability or regression of LM over at minimum the 3 months preceding screening
- Carcinoembryonic Antigen (CEA) values are stable or decreasing at all timepoints prior to the transplant surgery.
Exclusion Criteria:
- Previous or concurrent cancer (with some exceptions)
- prior lung resection
- Progression of LM at any timepoint prior to transplant surgery
- Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
- Pulmonary insufficiency
- History of cardiac disease
- Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B and/or C infection.
- Patients with debilitating neuropathy. (CTCAE > grade 2)
- BRAF + tumors
- Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
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）
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 |
|---|---|
|
実験的：transplantation
Live donor liver transplantation for the treatment of unresectable colorectal cancer liver metastases |
live donor liver transplantation |
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 |
時間枠 |
|---|---|
|
無病生存
時間枠：5年
|
5年
|
|
患者の生存
時間枠：5年
|
5年
|
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 |
|---|---|---|
|
無病生存
時間枠：3年
|
3年
|
|
|
無病生存
時間枠：1年
|
1年
|
|
|
患者の生存
時間枠：1年
|
1年
|
|
|
肝移植後のがん再発パターン
時間枠：5年
|
5年
|
|
|
がん再発治療の種類
時間枠：5年
|
5年
|
|
|
CTCAE v4.0によって評価された、化学療法関連の有害事象のために介入（移植手術）を受ける前に研究から脱落した参加者の数
時間枠：肝移植前
|
肝移植前
|
|
|
患者の生存
時間枠：3年
|
3年
|
|
|
self-reported quality of life as assessed by EORTC QLQ-C30 questionnaire
時間枠：6 month intervals for 5 years
|
Compare the QoL of participants undergoing intervention vs participants that drop-out (for non cancer related reasons and are thereafter receiving palliative chemotherapy) |
6 month intervals for 5 years
|
|
survival of intervention vs standard treatment
時間枠：1-, 3- and 5 years
|
Compare the 1-, 3- and 5- year survival of patients that undergo intervention with those that drop-out of the study (due to non-cancer related reasons and receive standard chemotherapy) |
1-, 3- and 5 years
|
協力者と研究者
捜査官
捜査官
- 主任研究者：Gonzalo Sapisochin, MD、University Health Network, Toronto
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)
研究開始
一次修了 (推定)
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 (推定)
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
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