Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer
Status: | Completed |
---|---|
Conditions: | Colorectal Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 8/23/2018 |
Start Date: | July 2005 |
End Date: | April 2015 |
Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, leucovorin, and
fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the
cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can
block tumor growth in different ways. Some block the ability of tumor cells to grow and
spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the
tumor. Giving bevacizumab together with combination chemotherapy may be a better way to block
tumor growth. Studying the amount of an enzyme found in the tumor may help doctors plan the
best treatment.
PURPOSE: This randomized phase II trial is studying giving bevacizumab, oxaliplatin, and
irinotecan or giving bevacizumab, oxaliplatin, leucovorin, and fluorouracil in treating
patients with metastatic or recurrent colorectal cancer.
fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the
cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can
block tumor growth in different ways. Some block the ability of tumor cells to grow and
spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the
tumor. Giving bevacizumab together with combination chemotherapy may be a better way to block
tumor growth. Studying the amount of an enzyme found in the tumor may help doctors plan the
best treatment.
PURPOSE: This randomized phase II trial is studying giving bevacizumab, oxaliplatin, and
irinotecan or giving bevacizumab, oxaliplatin, leucovorin, and fluorouracil in treating
patients with metastatic or recurrent colorectal cancer.
OBJECTIVES:
- Compare the response rate (complete and partial), progression-free survival, and overall
survival of patients with previously untreated metastatic or locally recurrent
colorectal adenocarcinoma with high vs low thymidylate synthase (TS) expression treated
with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab or irinotecan,
oxaliplatin, and bevacizumab.
- Compare the toxicity of these regimens in these patients.
- Correlate gene expression with response rates in patients treated with these regimens.
- Correlate gene expression with toxicity of these regimens in these patients.
- Correlate dihydropyrimidine dehydrogenase, thymidine phosphorylase, and mammalian
excision repair cross complementary protein expression with antitumor response in
patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
thymidylate synthase (TS) expression levels (high vs low or indeterminate). Patients with
high TS expression are randomized to 1 of 2 treatment arms (Arms A or B). Patients with low
or indeterminate TS expression are assigned to Arm C.
- Arm A: Patients receive bevacizumab IV over 30-90 minutes followed by oxaliplatin IV
over 2 hours and irinotecan IV over 90 minutes on days 1 and 15.
- Arm B: Patients receive bevacizumab and oxaliplatin as in arm A, leucovorin calcium IV
over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on
days 1 and 15.
- Arm C: Patients receive bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil
as in arm B.
In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease
progression.
Patients are followed up every 3 months for 2 years and then every 6 months for 2 years from
the date of study registration.
- Compare the response rate (complete and partial), progression-free survival, and overall
survival of patients with previously untreated metastatic or locally recurrent
colorectal adenocarcinoma with high vs low thymidylate synthase (TS) expression treated
with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab or irinotecan,
oxaliplatin, and bevacizumab.
- Compare the toxicity of these regimens in these patients.
- Correlate gene expression with response rates in patients treated with these regimens.
- Correlate gene expression with toxicity of these regimens in these patients.
- Correlate dihydropyrimidine dehydrogenase, thymidine phosphorylase, and mammalian
excision repair cross complementary protein expression with antitumor response in
patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
thymidylate synthase (TS) expression levels (high vs low or indeterminate). Patients with
high TS expression are randomized to 1 of 2 treatment arms (Arms A or B). Patients with low
or indeterminate TS expression are assigned to Arm C.
- Arm A: Patients receive bevacizumab IV over 30-90 minutes followed by oxaliplatin IV
over 2 hours and irinotecan IV over 90 minutes on days 1 and 15.
- Arm B: Patients receive bevacizumab and oxaliplatin as in arm A, leucovorin calcium IV
over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on
days 1 and 15.
- Arm C: Patients receive bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil
as in arm B.
In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease
progression.
Patients are followed up every 3 months for 2 years and then every 6 months for 2 years from
the date of study registration.
INCLUSION:
- Metastatic or locally recurrent colorectal adenocarcinoma
- Measurable disease
- At least 2 formalin-fixed paraffin embedded core needle biopsies OR fine needle
aspirate containing a minimum of 3 clusters of malignant cells and fixed tissue from
the previous biopsy
- If no tissue samples are available the patient must be willing to undergo biopsy of a
metastatic site
- Age 18 and over
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 unless patient is
receiving full-dose anticoagulants AND the following criteria are met:
- In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low
molecular weight heparin
- No active bleeding or pathological condition that is associated with a high risk
of bleeding
- Partial thromboplastin time (PTT) < 1.5 times upper limit of normal (ULN)
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 3 times ULN
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 1.8 mg/dL
- Meets 1 of the following criteria:
- Protein negative on urine dipstick
- Urine protein/creatinine ratio < 1.0
- Less than 2 g protein on 24-hour urine collection
- Patients with a history of hypertension must meet the following criteria:
- Blood pressure < 150/90 mm Hg
- Stable regimen of anti-hypertensive therapy
- More than 28 days since prior major or open surgery
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
participation
- Prior non-colorectal malignancies are allowed provided the following criteria are met:
- No current clinical evidence of persistent or recurrent disease
- No active therapy for non-colorectal malignancy, including hormonal therapy
EXCLUSION:
- Pregnant or nursing
- Arterial thromboembolic events within the past 6 months, including the following:
- Transient ischemic attack
- Cerebrovascular accident
- Unstable angina pectoris
- Myocardial infarction
- Symptomatic arrhythmia
- Symptomatic congestive heart failure
- Clinically significant peripheral artery disease
- New York Heart Association class III or IV heart disease
- Serious nonhealing wound, ulcer, or bone fracture within the past 28 days
- Significant traumatic injury within the past 28 days
- Neuropathy ≥ grade 2
- Ongoing or active infection
- Concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
- Prior chemotherapy for metastatic disease. Adjuvant therapy completed at least 12
months before first evidence of metastasis allowed
- Cardiovascular, renal, hepatic, or other nonmalignant systemic disease that would
preclude study therapy
We found this trial at
110
sites
401 Matthew St
Marietta, Ohio 45750
Marietta, Ohio 45750
(740) 376-5000
Strecker Cancer Center at Marietta Memorial Hospital The Memorial Health System's Strecker Cancer Center combines...
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1200 S Cedar Crest Blvd
Allentown, Pennsylvania 18103
Allentown, Pennsylvania 18103
(610) 402-8000
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest Lehigh Valley Hospital provides a...
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675 N Saint Clair St # 21-100
Chicago, Illinois 60611
Chicago, Illinois 60611
(312) 695-1156
Robert H. Lurie Comprehensive Cancer Center at Northwestern University The cancer center was first established...
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2500 Metrohealth Dr # C2100
Cleveland, Ohio 44109
Cleveland, Ohio 44109
(216) 778-5802
MetroHealth Cancer Care Center at MetroHealth Medical Center At the MetroHealth Cancer Care Center, we...
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3535 Olentangy River Road
Columbus, Ohio 43214
Columbus, Ohio 43214
(614) 566-5000
Riverside Methodist Hospital Cancer Care Serving central Ohio since 1892, Riverside Methodist is consistently ranked...
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1719 East 19th Avenue
Denver, Colorado 80218
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(303) 839-6000
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1376 Mowry Road
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West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
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Avera Cancer Institute Avera, the health ministry of the Benedictine and Presentation Sisters, is a...
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1365 Clifton Rd NE
Atlanta, Georgia 30322
Atlanta, Georgia 30322
(404) 778-1900
Winship Cancer Institute at Emory University Winship Cancer Institute of Emory University is Georgia
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11850 Blackfoot St. NW
Suite 130
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763-236-0808
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2300 N. Edward Street
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217-876-8121
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550 Osborne Road
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763-236-5000
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2635 North 7th Street
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535 Barnhill Dr
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(888) 600-4822
Indiana University Melvin and Bren Simon Cancer Center At the IU Simon Cancer Center, more...
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Borgess Medical Center At Borgess, healing is our calling. This is the place where people...
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100 Provena Way
Kankakee, Illinois 60914
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815.937.8780
Provena St. Mary's Regional Cancer Center - Kankakee For over 20 years, Presence St. Mary's...
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1007 LINCOLNWAY
La Porte, Indiana 46350
La Porte, Indiana 46350
219.326.1234
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1800 Hollister Drive, Suite 112
Libertyville, Illinois 60048
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847-367-6781
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1575 Beam Avenue
Maplewood, Minnesota 55109
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651-232-7970
HealthEast Cancer Care at St. John's Hospital From the moment patients and visitors walk into...
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90 Brick Rd
Marlton, New Jersey 08053
Marlton, New Jersey 08053
(856) 355-6000
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton Virtua collaborates with Fox...
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701 Park Ave
Minneapolis, Minnesota 55415
Minneapolis, Minnesota 55415
(612) 873-3000
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800 E 28th St
Minneapolis, Minnesota 55407
Minneapolis, Minnesota 55407
612-863-4000
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Saint Joseph Regional Medical Center Saint Joseph Regional Medical Center is a not-for-profit, multi-hospital health...
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1320 West Main Street
Newark, Ohio 43055
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(740) 348-4475
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8915 W Golf Rd
Niles, Illinois 60714
Niles, Illinois 60714
(847) 827-9060
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Omaha, Nebraska 68124
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(402) 398-6060
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1001 PENNSYLVANIA AVENUE
Ottumwa, Iowa 52501
Ottumwa, Iowa 52501
641.684.2300
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Spruce St
Reading, Pennsylvania 19611
Reading, Pennsylvania 19611
(484) 628-4357
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3435 W Broadway Ave
Robbinsdale, Minnesota 55422
Robbinsdale, Minnesota 55422
(763) 520-7887
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3535 N Bell School Rd
Rockford, Illinois 61114
Rockford, Illinois 61114
(779) 696-9400
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1455 St. Francis Ave.
Shakopee, Minnesota 55379
Shakopee, Minnesota 55379
952.428.2031
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100 Medical Center Drive
Springfield, Ohio 45504
Springfield, Ohio 45504
937-523-1000
Community Hospital of Springfield and Clark County For over 100 years, Springfield Regional Medical Center...
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Lakeview Hospital At Lakeview Hospital, our Mission is to provide the quality of healthcare we...
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