Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer (STEAM)
2017년 8월 18일 업데이트: Hoffmann-La Roche
Steam (Sequencing Triplet With Avastin and Maintenance): FOLFOXIRI/Bevacizumab Regimens (Concurrent and Sequential) vs. FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
This randomized, open-label, multicenter study will evaluate the efficacy and safety of folinic acid (leucovorin), 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) / bevacizumab regimens (concurrent and sequential) versus folinic acid (leucovorin), 5-fluorouracil, and oxaliplatin (FOLFOX) / bevacizumab in first-line in participants with metastatic colorectal cancer.
Participants will be randomized to receive bevacizumab 5 milligrams per kilogram (mg/kg) intravenously every 2 weeks with either concurrent or sequential FOLFOXIRI or with FOLFOX for 4 to 6 months of induction therapy, followed by maintenance therapy with bevacizumab plus either leucovorin/5-fluorouracil or capecitabine until disease progression occurs.
After disease progression, participants will receive treatment with a fluoropyrimidine-based chemotherapy plus bevacizumab.
연구 개요
상태
종료됨
정황
연구 유형
중재적
등록 (실제)
280
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Alabama
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Mobile, Alabama, 미국, 36604
- University of South Alabama; Mitchell Cancer Institute
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California
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Long Beach, California, 미국, 90806
- Long Beach Memorial Medical Center; Oncology
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Los Angeles, California, 미국, 90033
- USC Norris Cancer Center
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Los Angeles, California, 미국, 90033
- LAC-USC Medical Center
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Monterey, California, 미국, 93940
- Pacific Cancer Care - Monterey
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Sacramento, California, 미국, 95816
- Sacramento Center for Hematolo
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Salinas, California, 미국, 93901
- Pacific Cancer Care
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Colorado
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Denver, Colorado, 미국, 80205
- Kaiser Permanente - Franklin
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Connecticut
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New Haven, Connecticut, 미국, 06520
- Yale Cancer Center
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District of Columbia
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Washington, D.C., District of Columbia, 미국, 20016
- Sibley Memorial Hospital
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Florida
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Fort Myers, Florida, 미국, 33905
- Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
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Saint Petersburg, Florida, 미국, 33705
- Florida Cancer Specialist, North Region
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Georgia
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Athens, Georgia, 미국, 30607
- University Cancer & Blood Center, LLC
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Atlanta, Georgia, 미국, 30322
- Emory University Clinic
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Macon, Georgia, 미국, 31201
- Central Georgia Cancer Care PC
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Savannah, Georgia, 미국, 31405
- Summit Cancer Care PC
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Illinois
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Harvey, Illinois, 미국, 60426
- Ingalls Memorial Hosp
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Naperville, Illinois, 미국, 60540
- Edward Cancer Center Naperville
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Plainfield, Illinois, 미국, 60585
- Edward Cancer Center Plainfield
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Kentucky
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Lexington, Kentucky, 미국, 40536
- University of Kentucky Medical Center
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Maryland
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Baltimore, Maryland, 미국, 21231
- Johns Hopkins Univ; Bunting Blaustein Cancer Center
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Massachusetts
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Boston, Massachusetts, 미국, 02111
- Tufts Medical Center
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Michigan
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Ann Arbor, Michigan, 미국, 48106
- St. Joseph Mercy Hospital; Cancer Care Center.
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Detroit, Michigan, 미국, 48201
- Karmanos Cancer Institute..
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Missouri
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Saint Louis, Missouri, 미국, 63110
- Washington University School of Medicine
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Nebraska
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Lincoln, Nebraska, 미국, 68510
- Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
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Omaha, Nebraska, 미국, 68114
- Nebraska Methodist Hospital; Cancer Center
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New Hampshire
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Lebanon, New Hampshire, 미국, 03756
- Dartmouth Hitchcock Med Center
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Ohio
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Cincinnati, Ohio, 미국, 45242
- Oncology Hematology Care Inc
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Oklahoma
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Oklahoma City, Oklahoma, 미국, 73104
- University of Oklahoma; Stephenson Oklahoma Canc Ctr
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Pennsylvania
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Hershey, Pennsylvania, 미국, 17033
- Milton S. Hershey Medical Center; Penn State Cancer Inst.
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Tennessee
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Chattanooga, Tennessee, 미국, 37404
- Chattanooga Oncology and Hematology Associates, PC
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Germantown, Tennessee, 미국, 38138
- West Clinic
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Nashville, Tennessee, 미국, 37203
- Sarah Cannon Cancer Center and Research Institute
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Texas
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Dallas, Texas, 미국, 75390-9063
- UT Southwestern MC at Dallas
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Fort Worth, Texas, 미국, 76104
- Ctr For Cancer And Blood Disorders
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Temple, Texas, 미국, 76508
- Scott and White Hospital; Cancer Center
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Virginia
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Richmond, Virginia, 미국, 23226
- Virginia Cancer Institute
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Washington
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Kirkland, Washington, 미국, 98034
- Seattle Cancer Care Alliance - Evergreen Health
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Seattle, Washington, 미국, 98109
- Seattle Cancer Care Alliance
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Spokane, Washington, 미국, 99208
- Medical Oncology Associates
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Wisconsin
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Green Bay, Wisconsin, 미국, 54311
- Vince Lombardi Cancer Center
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Milwaukee, Wisconsin, 미국, 53226
- Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
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Wauwatosa, Wisconsin, 미국, 53226
- Aurora Research Institute
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Wyoming
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Cheyenne, Wyoming, 미국, 82001
- Cheyenne Oncology & Hematology Associates
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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 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Histologically confirmed colorectal cancer with at least one measurable metastatic lesion by RECIST v 1.1, that is considered unresectable at baseline
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 if age less than (<) 71 years; ECOG status of 0 if age 71 to 75 years
- Adequate hematological, renal and liver function
- Participants with treated brain metastases are eligible for study participation; participants may not receive ongoing treatment with steroids at screening, anticonvulsants (at stable dose) are allowed
- Females of childbearing potential and males must agree to use effective contraception as defined by protocol during the treatment period and for at least 6 months after the last dose of study drug
Exclusion Criteria:
- Any prior treatment for metastatic colorectal cancer, except for use of palliative radiosensitizers
- Adjuvant chemotherapy for colorectal cancer completed < 12 months prior to study consent
- Sensory peripheral neuropathy greater than or equal to (>/=) Grade 2
- Evidence of Gilbert's Syndrome or homozygosity for the Uridine 5-diphospho-glucuronosyltransferase (UGT) 1A1*28 allele
- Positive for human immunodeficiency virus (HIV) infection
- Malignancies other than metastatic colorectal cancer within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
- Radiotherapy to any site for any reason within 28 days prior to randomization, except for palliative radiotherapy to bone lesions within 14 days prior to randomization
- Clinically significant third-space fluid collections (e.g. ascites or pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry
- Treatment with any other investigational agent, or participation in another investigational drug trial within 28 days prior to randomization
- Any disease or condition or laboratory finding giving reasonable suspicion of disease or condition that contraindicates the use of bevacizumab or puts the participant at high risk for treatment-related complications
- Inadequately controlled hypertension
- Clinically significant (that is [i.e.] active) cardiovascular disease (For example [e.g.] cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association Class >/= II) or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with the administration of the study treatment
- Known hypersensitivity to bevacizumab or any of its excipients or any other study drug
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 |
|---|---|
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실험적: Arm A: Concurrent FOLFOXIRI + Bevacizumab
Participants will receive concurrent FOLFOXIRI along with 5 mg/kg of bevacizumab with treatment cycle of 2 weeks during first 4 month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase.
Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
|
Participants in Arm A will receive 3200 milligrams per square meter (mg/m^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks per investigator's discretion.
Participants in Arm B and C will receive a bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
다른 이름들:
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
다른 이름들:
Participants will receive IV infusion of 165 mg/m^2 over 1 hour every 2 weeks (Arm A) or IV infusion of 180 mg/m^2 over 1 hour in 2 x 2 weeks cycles alternating months (in Arm B), during 4-6 months induction phase.
Participants will receive IV infusion of 200 mg/m^² (Arm A) or 400 mg/m^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m^2 in the maintenance therapy.
다른 이름들:
Participants will receive 85 mg/m^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
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실험적: Arm B: Sequential FOLFOXIRI + Bevacizumab
Participants will receive alternating 4-week administrations of FOLFOX/bevacizumab and folinic acid (leucovorin), 5-FU, and irinotecan (FOLFIRI) /Bevacizumab with a treatment cycle of 2 weeks during first 4-month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase.
Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
|
Participants in Arm A will receive 3200 milligrams per square meter (mg/m^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks per investigator's discretion.
Participants in Arm B and C will receive a bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
다른 이름들:
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
다른 이름들:
Participants will receive IV infusion of 165 mg/m^2 over 1 hour every 2 weeks (Arm A) or IV infusion of 180 mg/m^2 over 1 hour in 2 x 2 weeks cycles alternating months (in Arm B), during 4-6 months induction phase.
Participants will receive IV infusion of 200 mg/m^² (Arm A) or 400 mg/m^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m^2 in the maintenance therapy.
다른 이름들:
Participants will receive 85 mg/m^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
|
|
실험적: Arm C: FOLFOX + Bevacizumab
Participants will receive FOLFOX along with 5 mg/kg of bevacizumab with treatment cycle of 2 weeks during first 4-month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase.
Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
|
Participants in Arm A will receive 3200 milligrams per square meter (mg/m^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks per investigator's discretion.
Participants in Arm B and C will receive a bolus dose of 400 mg/m^2, followed by a 46-hour continuous infusion (2400 mg/m^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
다른 이름들:
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
다른 이름들:
Participants will receive IV infusion of 200 mg/m^² (Arm A) or 400 mg/m^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m^2 in the maintenance therapy.
다른 이름들:
Participants will receive 85 mg/m^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Percentage of Participants With Overall Response During First-Line Therapy (ORR1)
기간: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
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ORR1 was the percentage of participants with complete response (CR) or partial response (PR) during first-line therapy as assessed by investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1).
CR was defined as disappearance of all extranodal target lesions and all pathological lymph nodes had to have decreased to <10 millimeter (mm) in short axis.
PR was defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum diameters.
ORR1 = CR + PR
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Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
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Progression-Free Survival During First-Line Therapy (PFS1)
기간: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
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PFS1 was defined as time from randomization to the first occurrence of disease progression during first-line therapy, as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurs first.
Disease progression was defined as sum of longest diameters increased by at least 20% from the smallest value on study.
The sum of longest diameters must also demonstrate an absolute increase of at least 5 mm.
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Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Time to PFS2
기간: Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years)
|
Time to PFS2 was defined as time from randomization to the first occurrence of disease progression after reinduction of second-line therapy, as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurs first.
Disease progression was defined as sum of longest diameters increased by at least 20% from the smallest value on study.
The sum of longest diameters must also demonstrate an absolute increase of at least 5mm.
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Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years)
|
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Overall Survival (OS)
기간: Randomization until death due to any cause (up to approximately 3 years)
|
OS was defined as the time from the date of randomization to the date of death from any cause.
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Randomization until death due to any cause (up to approximately 3 years)
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Proportion of Participants Who Underwent Liver Metastases Resections
기간: Randomization up to approximately 3 years
|
Reported here is the proportion of participants who underwent liver metastases resections calculated as follows: number of participants who underwent liver metastases resections divided by total number of participants in each arm.
|
Randomization up to approximately 3 years
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Proportion of Participants Considered by the Investigator to be Unresectable on Study Enrollment Who Subsequently Underwent Attempted Curative Resections of Metastases
기간: Randomization up to approximately 3 years
|
The proportion of participants considered by the investigator to be unresectable at study enrollment who subsequently underwent attempted curative resections of metastases was calculated as follows: number of participants considered by the investigator to be unresectable at study enrollment who subsequently underwent attempted curative resections of metastases divided by total number of participants in each arm.
This outcome represents a measure of the rate of conversion from unresectable to resectable disease.
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Randomization up to approximately 3 years
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Percentage of Participants With Adverse Events
기간: Randomization up to approximately 3 years
|
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment.
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
Preexisting conditions which worsen during a study are also considered as adverse events.
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Randomization up to approximately 3 years
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
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
- Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
- Hurwitz HI, Tan BR, Reeves JA, Xiong H, Somer B, Lenz HJ, Hochster HS, Scappaticci F, Palma JF, Price R, Lee JJ, Nicholas A, Sommer N, Bendell J. Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14.
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)
2013년 1월 23일
기본 완료 (실제)
2016년 3월 14일
연구 완료 (실제)
2016년 3월 14일
연구 등록 날짜
최초 제출
2013년 1월 9일
QC 기준을 충족하는 최초 제출
2013년 1월 9일
처음 게시됨 (추정)
2013년 1월 10일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 9월 18일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 8월 18일
마지막으로 확인됨
2017년 8월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- ML28442
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
예
미국 FDA 규제 기기 제품 연구
아니
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. .