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Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy in Treating Patients Who Are Undergoing Surgical Resection for Locally Advanced Rectal Cancer

2020年2月4日 更新者：Radiation Therapy Oncology Group

Randomized Phase II Trial Of Neoadjuvant Combined Modality Therapy For Locally Advanced Rectal Cancer

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Chemoradiotherapy (combining chemotherapy with radiation therapy) before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying two different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy and comparing how well they work in treating patients who are undergoing surgical resection for locally advanced rectal cancer.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

OBJECTIVES:

  • Evaluate the pathologic complete response rate in patients with locally advanced rectal cancer undergoing surgical resection treated with 2 different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy.
  • Evaluate the time to treatment failure and patterns of failure in patients treated with these regimens.
  • Evaluate the incidence of hematologic and non-hematologic grade 3-4 toxicity (preoperatively, postoperatively, and overall) in patients treated with these regimens.
  • Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical stage of tumor (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.

Quality of life is assessed at baseline, within 1 week after completion of radiotherapy, within 1 week after completion of adjuvant chemotherapy (12 months), and then at 24 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

研究の種類

介入

入学 (実際)

146

段階

  • フェーズ2

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

  • アメリカ
    • California
      • Sacramento、California、アメリカ、95817
        • University of California Davis Cancer Center
    • Florida
      • Miami、Florida、アメリカ、33176
        • Baptist-South Miami Regional Cancer Program
    • Illinois
      • Harvey、Illinois、アメリカ、60426
        • Ingalls Cancer Care Center at Ingalls Memorial Hospital
    • New Jersey
      • Marlton、New Jersey、アメリカ、08053
        • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
    • Pennsylvania
      • Dunmore、Pennsylvania、アメリカ、18512
        • Northeast Radiation Oncology 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. Adenocarcinoma of the rectum originating at or below 12 cm from the anal verge without evidence of distant metastases
  2. Patient must be 18 years of age or greater.
  3. Potentially resectable en bloc based upon surgeon evaluation
  4. Clinical stages T3 or T4, based upon endorectal ultrasound, or physical examination (only acceptable for T4 lesions).

  5. Absolute neutrophil count of > 1500 per microliter and platelet count > 100,000 per microliter; aspartate aminotransferase (AST) and alkaline phosphatase < 2.5 X upper limit of normal (ULN), bilirubin < = 1.5 ULN, calculated creatinine clearance > 50 ml/min using Cockcroft-Gault formula:

    • CrCl male = (140 - age) x (wt. in kg) / (Serum Cr) x 72
    • CrCl female = 0.85 x (CrCl male)
  6. Zubrod performance status 0-2
  7. No history of other malignancies within 5 years, except non-melanoma skin cancer, in situ carcinoma of the cervix, or ductal carcinoma in situ of the breast. Previous invasive cancer permitted if disease free at least 5 years.
  8. Signed study-specific informed consent prior to randomization

Exclusion Criteria:

  1. Any evidence of distant metastasis
  2. Synchronous primary colon carcinomas, except T1 lesions (full colonoscopy not required for enrollment)
  3. Extension of malignant disease to the anal canal
  4. Prior radiation therapy to the pelvis
  5. Prior chemotherapy for malignancies
  6. Pregnancy or lactation, (exclusion due to potential adverse effects of therapy). Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. Women/men of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered to be of non-childbearing potential.) Patients will agree to continue contraception for 30 days from the date of the last study drug administration.
  7. Serious, uncontrolled, concurrent infection(s).
  8. Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
  9. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
  10. Evidence of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
  11. Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
  12. Major surgery within 4 weeks of the study treatment.
  13. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
  14. Known, existing uncontrolled coagulopathy.
  15. No concurrent cimetidine allowed.

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：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：Neoadjuvant chemoradiation with irinotecan
Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1200mg/m^2/day 5 days/week during RT, and irinotecan 50 mg/m^2 IV for 1 hour days 1, 8, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) .
放射線：Radiation Therapy
Pelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy.
薬：Capecitabine 1200 mg/m^2/day
600 mg/m^2 q12 hours(1200 mg/m^2/day) orally 5 days per week during radiotherapy.
薬：Irinotecan
50mg/m^2 IV over 1 hour on days 1, 8, 22, and 29
他の名前：
  • イリノテカン塩酸塩
薬：Oxaliplatin
50mg/m^2 IV over 2 hours on days 1, 8, 15, 22, and 29
手順：Surgery
All patients will undergo surgery four to eight weeks following the completion of radiation therapy. The choice of procedure abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis is at the discretion of the surgeon.
薬：Folinic Acid
400 mg/m^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles.
他の名前：
  • ロイコボリン
薬：Fluorouracil

5-fluorouracil bolus 400 mg/m^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

5-fluorouracil infusion 2400 mg/m^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles.

他の名前：
  • 5-FU
薬：Oxaliplatin
85 mg/m^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.
実験的：Neoadjuvant chemoradiation with oxaliplatin
Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1650mg/m^2/day 5 days/week during RT, and oxaliplatin 50 mg/m^2 IV for 2 hours days 1, 8, 15, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) .
放射線：Radiation Therapy
Pelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy.
薬：Oxaliplatin
50mg/m^2 IV over 2 hours on days 1, 8, 15, 22, and 29
手順：Surgery
All patients will undergo surgery four to eight weeks following the completion of radiation therapy. The choice of procedure abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis is at the discretion of the surgeon.
薬：Folinic Acid
400 mg/m^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles.
他の名前：
  • ロイコボリン
薬：Fluorouracil

5-fluorouracil bolus 400 mg/m^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

5-fluorouracil infusion 2400 mg/m^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles.

他の名前：
  • 5-FU
薬：Oxaliplatin
85 mg/m^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.
薬：Capecitabine 1650 mg/m^2/day
825 mg/m^2 q12 hours (1650 mg/m^2/day) orally 5 days per week during radiotherapy.

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
Pathologic Complete Response Rate
時間枠：After protocol surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation

A pathologic complete response (pCR) was defined as no evidence of residual cancer histologically; disease progression or death before surgery was considered less than pCR (even without surgical specimen). All cases were reviewed by the study's surgical oncology co-chair for the determination of pCR.

Each arm was first analyzed alone. If the arm had 9 or more pCRs in 48 evaluable pts, then the null hypothesis (H0) of 10% pCR rate would be rejected in favor of the alternative hypothesis of 25%, providing 90% power with a two-sided 10% type I error rate. If both arms reject H0, then statistical selection theory would be used to choose the arm for further study in a phase III trial. If only one arm has acceptable pCR rate, then that arm would be pursued in a phase III trial.
After protocol surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation

二次結果の測定

結果測定
メジャーの説明
時間枠
Survival Rate at 4 Years
時間枠：From randomization to four years
Survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method.
From randomization to four years
Local-regional Failure Rate at 4 Years
時間枠：From randomization to four years
Local-regional failure is defined as any of the following: no clinical complete response (cCR) in the primary site and/or nodes at any time after treatment completion (persistence), recurrence and/or progression in the primary site and/or nodes after cCR, and nonprotocol surgery to the primary site after cCR. Time to local-regional failure is defined as time from randomization to date of failure, last known follow-up (censored), or death without local-regional failure (competing risk). Local-regional failure rates are estimated by the cumulative incidence method.
From randomization to four years
Distant Failure Rate at 4 Years
時間枠：From randomization to four years
Time to distant failure is defined as time from randomization to date of the appearance of distant metastases, last known follow-up (censored), or death without distant failure (competing risk). Distant failure rates are estimated by the cumulative incidence method.
From randomization to four years
Second Primary Rate at 4 Years
時間枠：From randomization to four years
Time to second primary is defined as time from randomization to date of the appearance of a second primary cancer, last known follow-up (censored), or death without second primary (competing risk). Second primary rates are estimated by the cumulative incidence method.
From randomization to four years
Disease-free Survival Rate at 4 Years
時間枠：From randomization to four years
Disease-free survival time is defined as time from randomization to date of local-regional failure, the appearance of distant metastases, the appearance of a second primary failure, or date of death from any cause/ Disease-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact.
From randomization to four years
Number of Participants With Grade 3+ Treatment-related Adverse Events
時間枠：From start of treatment to end of follow-up. Maximum follow-up is 5.2 years.
Highest grade adverse event per subject were counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
From start of treatment to end of follow-up. Maximum follow-up is 5.2 years.
Number of Participants With Grade 3+ Treatment-related Adverse Events Preoperatively
時間枠：From start of treatment to surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation. If no surgery, then <= 90 days from start of treatment.
Highest grade adverse event per subject were counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
From start of treatment to surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation. If no surgery, then <= 90 days from start of treatment.
Number of Participants With Grade 3+ Treatment-related Adverse Events Postoperatively
時間枠：From post-surgery to before chemotherapy (CT), or within 60 days of surgery if no postoperative CT. Approximately 10-16 weeks to 14-22 weeks from randomization based on CT starting 4-6 weeks after surgery.
Highest grade adverse event per subject were counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
From post-surgery to before chemotherapy (CT), or within 60 days of surgery if no postoperative CT. Approximately 10-16 weeks to 14-22 weeks from randomization based on CT starting 4-6 weeks after surgery.
Tumor Marker Evaluation Using Preoperative Tissue Biopsy Specimens and Surgically Resected Tissue Specimens
時間枠：End of study
End of study
Change From Baseline in QLQ-C30 Global Health Status Score at Completion of Chemoradiation
時間枠：Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates decline in quality of life. A positive number indicates improvement in QOL.
Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
Change From Baseline in QLQ-C30 Global Health Status Score at Completion of Post-operative Chemotherapy
時間枠：Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates decline in quality of life. A positive number indicates improvement in QOL.
Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in QLQ-C30 Global Health Status Score at Two Years
時間枠：Baseline and two years
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates decline in quality of life. A negative number indicates improvement in symptoms.
Baseline and two years
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Completion of Chemoradiation
時間枠：Baseline and completion of chemoradiation approximately 6-8 weeks from randomization
The gastro-intestinal (GI) symptom score is calculated from five symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 (not at all) to 4 (very much) such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Baseline and completion of chemoradiation approximately 6-8 weeks from randomization
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Completion of Post-operative Chemotherapy
時間枠：Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
The gastro-intestinal (GI) symptom score is calculated from five symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 (not at all) to 4 (very much) such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Two Years
時間枠：Baseline and two years
The gastro-intestinal (GI) symptom score is calculated from five symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 (not at all) to 4 (very much) such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Baseline and two years
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Completion of Chemoradiation
時間枠：Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
The defecation symptom score is calculated from seven symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 "not at all" to 4 "very much" such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Post-operative Chemotherapy
時間枠：Baseline and completion of post-operative chemotherapy, approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
The defecation symptom score is calculated from seven symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 "not at all" to 4 "very much" such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Baseline and completion of post-operative chemotherapy, approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Two Years
時間枠：Baseline and two years
The defecation symptom score is calculated from seven symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 "not at all" to 4 "very much" such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Baseline and two 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

Radiation Therapy Oncology Group

協力者

National Cancer Institute (NCI)

捜査官

  • 主任研究者：Neal J. Meropol, MD、Fox Chase Cancer Center

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

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

2004年3月1日

一次修了 (実際)

2011年5月1日

研究の完了 (実際)

2016年12月1日

試験登録日

最初に提出

2004年4月7日

QC基準を満たした最初の提出物

2004年4月7日

最初の投稿 (見積もり)

2004年4月8日

学習記録の更新

投稿された最後の更新 (実際)

2020年2月27日

QC基準を満たした最後の更新が送信されました

2020年2月4日

最終確認日

2020年2月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • RTOG-0247
  • CDR0000350136

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。

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