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Paclitaxel Followed by FEC Versus Paclitaxel and RAD001 Followed by FEC In Women With Breast Cancer

2016년 9월 12일 업데이트: M.D. Anderson Cancer Center

Open Label Randomized Clinical Trial of Standard Neoadjuvant Chemotherapy (Paclitaxel Followed by FEC) Versus the Combination of Paclitaxel and RAD001 Followed by FEC in Women With Triple Receptor-Negative Breast Cancer (CRAD001C24101)

The goal of this clinical research is to learn if RAD001 given in combination with chemotherapy will turn off the signaling pathway (a chain of information that tells cancer cells to grow quickly) and make the chemotherapies given on this study more effective.

Primary Objective

· To determine if the addition of an mTOR inhibitor to standard neoadjuvant chemotherapy in patients with triple receptor-negative breast cancer causes molecular changes (inhibition/activation) of the PI3K/PTEN/AKT pathway.

Secondary Objectives

  • To evaluate pathologic complete response (pCR) rates for each treatment group.
  • To evaluate the relationship between pCR and the molecular changes (inhibition/activation) of the PI13K/PTEN/AKT pathway in each treatment group.
  • To evaluate overall response rates (ORR) for each treatment group.
  • To assess the toxicity of both regimens and to evaluate the relationship of toxicities with PI3K/PTEN/AKT pathway status.

연구 개요

상태

알려지지 않은

정황

개입 / 치료

상세 설명

RAD001 is a new drug that was designed to block proteins that are important in the development and growth of cancer. It may also stop the growth of new blood vessels that help tumor growth, resulting in cell death.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a complete physical exam. Blood (about 6 tablespoons) will be drawn for routine tests and to test for the amount of fat in the blood. You will have a chest x-ray, bone scan and a 2-D echocardiogram (a test to evaluate the pumping function of the heart). You will have a computed tomography (CT) scan of the chest and abdomen (stomach area). Women who are able to have children must have a negative blood (about 1 tablespoon) pregnancy test.

You will have a mammogram and an ultrasound of the breast and armpit to record tumor size. As part of this study, you will have a fine needle biopsy of the breast tumor to test for the signaling pathway. You will receive a separate consent form for the mammogram, ultrasound, and biopsy and these procedures will be discussed with you in more detail. The fine needle biopsy is a procedure that would not be performed if you were not on this study.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. You will have an equal chance of being assigned to either group.

If you are assigned to Group 1, you will receive paclitaxel once a week through a needle in your vein over 1 hour. You will have a total of 12 treatments. Before each treatment, you may also receive drugs to help prevent or reduce your risk of side effects from paclitaxel.

If you are assigned to Group 2, you will receive paclitaxel and RAD001. You will receive paclitaxel once a week through a needle in your vein over 1 hour. You will have a total of 12 treatments. Before each treatment, you may also receive drugs to help prevent or reduce your risk of side effects from paclitaxel. You will take RAD001, by mouth, on each day you receive paclitaxel. You should take RAD001 on an empty stomach or after a light meal. Pills will not be taken out of their package until the staff is ready for you to take them, since they can be damaged by light or humidity.

Participants in both groups will have blood (about 2 tablespoons) drawn for routine tests before each weekly dose of chemotherapy.

You will have a second fine needle biopsy 2 days after starting treatment. This will be done to check to see if the signaling pathway has been affected.

After your 12 weeks of treatment with paclitaxel or paclitaxel and RAD001, you will have an ultrasound and if tumor is visible, a fine needle biopsy to check to see if the signaling pathway has been affected.

After the 12 week treatment with either paclitaxel or paclitaxel and RAD001, you will begin treatment with 5-fluorouracil, epirubicin, and cyclophosphamide. This drug combination is called FEC. You will receive FEC through needle in your vein (over 1 hour) once every 3 weeks. You will have 4 treatments (12 weeks total). Before each treatment, you may also receive drugs to help prevent or reduce your risk of side effects from FEC.

Once you have finished treatment with FEC, you will have a mammogram and ultrasound to check the status of the disease. This mammogram and ultrasound will also be used by the doctor to decide whether to remove all or part of the breast and/or nearby lymph nodes during surgery.

You will then have surgery to remove all or part of the breast that has the tumor. If there are signs that the lymph nodes in the armpit contain cancer, these lymph nodes will also be removed. You will receive a separate consent form for these procedures and your doctor will discuss them in more detail. If available, a portion of left over tumor tissue will be collected to check to see if the signaling pathway has been affected.

You will be considered "off study" once you have had surgery. You will be taken off study early if the disease gets worse or intolerable side effects occur.

This is an investigational study. Paclitaxel, 5-fluorouracil, cyclophosphamide, and epirubicin are all FDA approved and commercially available. RAD001 is not FDA approved or commercially available. It has been authorized for use in research only. Up to 50 patients will take part in this study. All will be enrolled at M. D. Anderson.

연구 유형

중재적

등록 (실제)

62

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 미국
    • Texas
      • Houston, Texas, 미국, 77030
        • University of Texas MD Anderson Cancer Center

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

여성

설명

Inclusion Criteria:

  1. Patients with histologic confirmation of invasive ER/PR and HER2/neu-negative breast carcinoma. Immunohistochemistry (IHC) must be used for ER/PR evaluation and IHC or FISH for determination of HER2/neu. ER/PR will be considered negative if equal or lower than 5% IHC staining and HER2/neu will be considered negative if IHC of 0% or negative FISH.
  2. Patients must have intact primary tumors.
  3. Age equal or greater than 18 years
  4. Patients should have stage IIA (T1N1) to IIIC non inflammatory breast cancer.
  5. Patients with bilateral breast cancers are eligible.
  6. Patients should have a Karnofsky performance scale of =/> 70%.
  7. Patients must have clinically measurable disease to be treated in the neoadjuvant setting. This includes patients with a non-palpable primary tumor who have histologically proven lymph node involvement that is clinically palpable and measurable by ultrasound.
  8. Patients should have adequate bone marrow function, as defined by peripheral granulocyte count of >/= 1500/mm3, and a platelet count >/= 100000/ mm3.
  9. Patients must have adequate liver function with a bilirubin within normal laboratory values. Alkaline phosphatase and transaminases (ALT and AST) may be up to 1.5 x upper limit of normal (ULN) of the institution.
  10. Patients should have adequate renal function with creatinine levels 2.0 mg/dL or lower
  11. Patients should have a normal left ventricular ejection fraction of =/> 50%.
  12. Negative serum pregnancy test for a woman of childbearing potential.
  13. Women of childbearing potential (WOCBP) must use a reliable and appropriate contraceptive method during the study and 6 months after chemotherapy is completed. WOCBP are women who are not menopausal for 12 months or had no previous surgical sterilization.
  14. Patients must agree to have study biopsies.
  15. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.
  16. Hemoglobin 9.0 gm/dL or higher

Exclusion Criteria:

  1. Patients whose tumors express ER, PR or HER2/neu gene amplification.
  2. Patients with a history of other invasive malignancies diagnosed and treated within the previous 5 years, except non-melanoma skin cancer and non-invasive cervical cancer
  3. Patients with an organ allograft or other history of immune compromise
  4. Prior exposure to mTOR inhibitors
  5. Hypersensitivity to rapamycin or other similar compounds
  6. Prior treatment with any investigational drug within the preceding 4 weeks
  7. Chronic treatment with systemic steroids or another immunosuppressive agent
  8. A known history of HIV seropositivity
  9. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  10. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin defined as 1 mg a day).
  11. Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration)
  12. Patients with a pre-existing peripheral neuropathy > grade 1
  13. Patients taking medications metabolized by the CYP3A4 subfamily will not be included in this study.

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: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Paclitaxel + FEC
Paclitaxel 80 mg/m^2 intravenously (IV) on day 1(+/- 2 days) of each week, followed by four cycles of combination 5-Fluorouracil at 500 mg/m^2, Epirubicin at 100 mg/m^2 and Cyclophosphamide at 500 mg/m^2 (FEC) on day 1 every 3 weeks (+/- 7 days).
의약품: Paclitaxel
80 mg/m^2 by vein once weekly over 1 hour on day 1(+/- 2 days) each week for 3 weeks and for 12 cycles.
다른 이름들:
  • 탁솔
의약품: 5-Fluorouracil
500 mg/m^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.
다른 이름들:
  • 5-FU
  • 아드루실
  • 에퓨덱스
의약품: Epirubicin
100 mg/m^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.
의약품: Cyclophosphamide
500 mg/m^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.
다른 이름들:
  • 사이톡산®
  • 네오사르®
실험적: Paclitaxel + RAD001 + FEC
Paclitaxel + RAD001 Followed by FEC (5-Fluorouracil + Epirubicin + Cyclophosphamide)
의약품: Paclitaxel
80 mg/m^2 by vein once weekly over 1 hour on day 1(+/- 2 days) each week for 3 weeks and for 12 cycles.
다른 이름들:
  • 탁솔
의약품: 5-Fluorouracil
500 mg/m^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.
다른 이름들:
  • 5-FU
  • 아드루실
  • 에퓨덱스
의약품: Epirubicin
100 mg/m^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.
의약품: Cyclophosphamide
500 mg/m^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.
다른 이름들:
  • 사이톡산®
  • 네오사르®
의약품: RAD001
30 mg by mouth weekly on Days 1, 8, & 15 for 12 cycles.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Number Participants With Inhibition of PI3K/PTEN/AKT Pathway at 48 Hours
기간: 48 hours after start of treatment
Number of participants with inhibition of the PI3K/PTEN/AKT pathway at 48 hours after the start of treatment, regardless of the status of the pathway at the time of randomization. Molecular changes (inhibition/activation) of the PI3K/PTEN/AKT pathway evaluated using reverse phase protein arrays (RPPA) where fine-needle aspirations (FNAs) from the primary breast cancer obtained pretreatment, and at 48 hours. Bioinformatics cluster analysis of arrays used to define molecular changes as inhibition or activation where pathways called 'active' with presence of 2 or more phosphorilated pathway proteins (pAKT, pmTOR, pGSK3, pS6K1, pS6), and 'inhibited' with one or none phosphorilated pathway proteins present.
48 hours after start of treatment

2차 결과 측정

결과 측정
측정값 설명
기간
Participant Responses Per Treatment Arm at 12 Weeks
기간: 12 weeks
Radiographic criteria of response based on regional ultrasound examination (decrease in size of the primary tumor and/or fatty replacement in regional lymph nodes), and includes partial response and complete response. A decrease in size of the product of the two largest dimensions =/> 50% considered a partial response (PR), and a complete disappearance of the primary tumor by physical exam and or ultrasound and normalization of the lymph nodes by ultrasound will be considered a complete clinical response (CR). Stable Disease (SD) is carcinoma neither decreasing nor increasing in extent or severity, and Progression of disease (PD) defined as 30% increase in size primary tumor and/or lymph nodes on physical exam and/or ultrasound.
12 weeks
Participant Responses Per Treatment Arm at 24 Weeks
기간: 24 weeks
Radiographic criteria of response based on regional ultrasound examination (decrease in size of the primary tumor and/or fatty replacement in regional lymph nodes), and includes partial response and complete response. A decrease in size of the product of the two largest dimensions =/> 50% considered a partial response (PR), and a complete disappearance of the primary tumor by physical exam and or ultrasound and normalization of the lymph nodes by ultrasound will be considered a complete clinical response (CR). Stable Disease (SD) is carcinoma neither decreasing nor increasing in extent or severity, and Progression of disease (PD) defined as 30% increase in size primary tumor and/or lymph nodes on physical exam and/or ultrasound.
24 weeks

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

M.D. Anderson Cancer Center

협력자

National Cancer Institute (NCI)
Novartis

수사관

  • 수석 연구원: Stacy Moulder, M.D., M.D. Anderson Cancer Center

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

유용한 링크

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

2007년 7월 1일

기본 완료 (실제)

2012년 4월 1일

연구 완료 (예상)

2017년 4월 1일

연구 등록 날짜

최초 제출

2007년 7월 9일

QC 기준을 충족하는 최초 제출

2007년 7월 9일

처음 게시됨 (추정)

2007년 7월 11일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2016년 11월 1일

QC 기준을 충족하는 마지막 업데이트 제출

2016년 9월 12일

마지막으로 확인됨

2016년 9월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 2006-0790
  • NCI-2012-01514 (레지스트리 식별자: NCI CTRP)
  • 1K23CA121994-1 (기타 보조금/기금 번호: NCI)
  • 1K23CA121994 (미국 NIH 보조금/계약)

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. .

유방암에 대한 임상 시험

Paclitaxel에 대한 임상 시험

유사한 임상시험 검색

스폰서 및 공동 작업자

건강 상태

약물 개입

CROs by country

CROs in Lebanon

정황

희귀 질병

약물 개입

식이 보충제

스폰서 / 협력자

위치

3
구독하다