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Oxaliplatin, Fluorouracil, Erlotinib Hydrochloride, and Radiation Therapy Before Surgery and Erlotinib Hydrochloride After Surgery in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

2018년 6월 29일 업데이트: Wake Forest University Health Sciences

A Phase I Study of Preoperative Chemoradiation With Oxaliplatin, 5-Fluorouracil, Erlotinib and Radiation Followed by Resection and Consolidative Erlotinib for Patients With Locally Advanced Cancer of the Esophagus and Gastroesophageal Junction

This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with oxaliplatin, fluorouracil, and radiation before surgery and alone after surgery in treating patients with locally advanced cancer of the esophagus and gastroesophageal junction. Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with erlotinib hydrochloride and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving erlotinib hydrochloride after surgery may kill any tumor cells that remain after surgery

연구 개요

상세 설명

OBJECTIVES:

I. The primary aim of this phase I study is to evaluate the safety of multi-drug chemotherapy (with the addition of an anti-epidermal growth factor receptor [EGFR] agent erlotinib [erlotinib hydrochloride]) and concomitant radiotherapy followed by resection and consolidative erlotinib for the treatment of locally advanced esophageal cancer as judged by the dose limiting toxicities. Correlative endpoints include an analysis of pre-treatment tumor cyclin D1 expression and EGFR expression/amplification.

III. Correlate pathologic complete response with changes in fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)-computed tomography (CT) - pre and post-chemoradiation.

OUTLINE: This is a dose escalation study of erlotinib hydrochloride

CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD), 5 days a week and receive fluorouracil intravenously (IV) continuously and erlotinib hydrochloride orally (PO) QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29.

SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially resectable disease (i.e., complete response, partial response, or stable disease) undergo surgery to remove the tumor.

CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

연구 유형

중재적

등록 (실제)

9

단계

  • 1단계

연락처 및 위치

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연구 장소

    • North Carolina
      • Winston-Salem, North Carolina, 미국, 27157
        • Wake Forest University Health Sciences

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Newly diagnosed patients with locally advanced esophageal cancer with either squamous or adenocarcinoma histology; patients should have evidence of extension of disease into or through the wall of the esophagus (T2-4) and/or regional nodal metastasis (N1)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Non-pregnant; patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method); nursing mothers are also ineligible
  • Prior treatment: Greater than one week shall have elapsed since any major surgery; no prior chemotherapy or radiotherapy is allowed
  • Adequate whole blood cell (WBC) and platelets (Plt) as determined by medical oncology
  • Serum creatinine =< 1.5 mg/dl
  • Creatinine clearance >= 60 ml/min
  • Hemoglobin (Hgb) >= 9.0 gm/dl
  • Absolute neutrophil count >= 1,500/uL
  • Serum total bilirubin =< 1.5 mg/dL
  • Alkaline phosphatase =< 3X the upper limit of normal (ULN) for the reference lab
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than 2X ULN for the reference laboratory
  • Patients must be told of the investigational nature of the study and must sign a written informed consent
  • No serious medical or psychiatric illnesses which would prevent informed consent or otherwise limit survival to less than two years; no history of refractory congestive heart failure or cardiomyopathy
  • Patients should be evaluated by medical oncology, radiation oncology, and surgery, and felt to by all to be suitable for trimodality therapy

Exclusion Criteria:

Patients with an active infection or with a fever >= 38.5 degrees Celsius (C) within 3 days of the first scheduled day of protocol treatment

  • History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate surface antigen (PSA) of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry
  • Patients with known hypersensitivity to any of the components of oxaliplatin
  • Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)
  • Peripheral neuropathy >= Grade 2
  • History of allogeneic transplant
  • Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
  • Pregnancy

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Treatment (chemotherapy, enzyme inhibitor therapy)

CHEMORADIOTHERAPY: Patients undergo radiation therapy QD, 5 days a week and receive fluorouracil IV continuously and erlotinib hydrochloride PO QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29.

SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially resectable disease (i.e., complete response, partial response, or stable disease) undergo surgery to remove the tumor.

CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks.

주어진 IV
다른 이름들:
  • 1-OHP
  • 다코틴
  • 닥플라
  • 엘록사틴
  • L-OHP
주어진 IV
다른 이름들:
  • 5-FU
  • 5-플루오로우라실
  • 5-플루라실
방사선 치료를 받다
다른 이름들:
  • 조사
  • 방사선 요법
  • 치료, 방사선
주어진 PO
다른 이름들:
  • OSI-774
  • 엘로티닙
  • CP-358,774
상관 연구
상관 연구
다른 이름들:
  • 면역조직화학
Undergo surgical resection
다른 이름들:
  • 수술, 재래식
Correlative study
다른 이름들:
  • 애완 동물
  • FDG-펫
  • PET 스캔
  • 단층 촬영, 방출 계산
Correlative study
다른 이름들:
  • 단층 촬영, 계산
Correlative study
Undergo F18 PET and CT scan
다른 이름들:
  • 18FDG
  • FDG

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Toxicity rate of combination chemotherapy followed by surgery and erlotinib hydrochloride
기간: Approximately 6 months
Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting (CTCAE v3.0). The dose limiting toxicity will be defined as any of the following that can be attributal to therapy: Any grade 4 neutropenia and or any grade 4 thrombocytopenia, or any >= grade 3 non-hematologic toxicity that results in a greater than 3 day interruption of therapy.
Approximately 6 months

2차 결과 측정

결과 측정
기간
Time to progression
기간: Approximately 4 years
Approximately 4 years
Survival
기간: Approximately 4 years
Approximately 4 years
Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)
기간: Over 4 years
Over 4 years
Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)
기간: Approximately 1 year
Approximately 1 year
Test the predictive value of FDG-PET-CT imaging in identifying patients who will have a complete response
기간: Approximately 1 year
Approximately 1 year

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2007년 4월 1일

기본 완료 (실제)

2009년 3월 1일

연구 완료 (실제)

2009년 3월 1일

연구 등록 날짜

최초 제출

2012년 2월 14일

QC 기준을 충족하는 최초 제출

2012년 3월 21일

처음 게시됨 (추정)

2012년 3월 22일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2018년 7월 2일

QC 기준을 충족하는 마지막 업데이트 제출

2018년 6월 29일

마지막으로 확인됨

2018년 6월 1일

추가 정보

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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