Bevacizumab, Radiation Therapy, and Combination Chemotherapy in Treating Patients Who Are Undergoing Surgery for Locally Advanced Nonmetastatic Rectal Cancer
Status: | Completed |
---|---|
Conditions: | Colorectal Cancer, Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 3/29/2019 |
Start Date: | July 25, 2006 |
End Date: | February 11, 2019 |
Phase II Study of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin and Bevacizumab Followed by Surgery and Postoperative 5-FU, Leucovorin, Oxaliplatin (FOLFOX) and Bevacizumab in Patients With Locally Advanced Rectal Cancer
This phase II trial studies how well giving bevacizumab, radiation therapy, and combination
chemotherapy works in treating patients who are undergoing surgery for locally advanced
nonmetastatic rectal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor
growth in different ways. Some find tumor cells and kill them or carry tumor-killing
substances to them. Others interfere with the ability of tumor cells to grow and spread.
Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.
Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as capecitabine,
may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as
capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the
growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving
bevacizumab together with radiation therapy and combination chemotherapy before surgery may
make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Giving bevacizumab together with combination chemotherapy after surgery may kill any tumor
cells that remain after surgery.
chemotherapy works in treating patients who are undergoing surgery for locally advanced
nonmetastatic rectal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor
growth in different ways. Some find tumor cells and kill them or carry tumor-killing
substances to them. Others interfere with the ability of tumor cells to grow and spread.
Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.
Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as capecitabine,
may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as
capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the
growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving
bevacizumab together with radiation therapy and combination chemotherapy before surgery may
make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Giving bevacizumab together with combination chemotherapy after surgery may kill any tumor
cells that remain after surgery.
PRIMARY OBJECTIVES:
I. To evaluate the pathological complete response rate in patients with T3 and T4 rectal
cancers when treated preoperatively with capecitabine, oxaliplatin, bevacizumab, and
concurrent radiotherapy (XRT).
II. To evaluate the resection rate for T3 and T4 rectal cancers and the expected versus
actual type of resection (abdominoperinal resection [APR] vs. low anterior resection [LAR]
vs. LAR/coloanal anastomosis).
III. To make preliminary observations of patient survival and patterns of recurrence for this
treatment combination.
IV. To gain additional experience regarding the toxicity and tolerability of this
preoperative and postoperative regimen.
OUTLINE:
PREOPERATIVE CHEMORADIOTHERAPY: Patients undergo radiotherapy (total dose to the tumor bed
was 5040 cGy) once daily (QD) 5 days a week and receive capecitabine 825 mg/m^2 orally (PO)
twice daily (BID) 5 days a week for 5.5 weeks. Patients also receive oxaliplatin 50 mg/m^2
intravenously (IV) over 2 hours on days 1, 8, 15, 22, and 29 and bevacizumab 5 mg/kg IV over
30-90 minutes on days 1, 15, and 29 during radiotherapy.
SURGERY: Approximately 6-8 weeks after completion of chemoradiotherapy, patients undergo
surgical resection. Patients whose tumors are not completely resected or who have metastatic
disease discontinue protocol therapy.
POSTOPERATIVE CHEMOTHERAPY: Approximately 4-12 weeks after surgery, patients receive
oxaliplatin IV over 2 hours, leucovorin calcium 400 mg/m^2 IV over 2 hours, and bevacizumab 5
mg/kg IV over 30-90 minutes on day 1. Patients also receive fluorouracil 2400 mg/m^2 IV
continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 9 courses
in the absence of disease progression or unacceptable toxicity. Patients then receive up to 3
additional courses of leucovorin calcium, fluorouracil, and bevacizumab.
After completion of study treatment, patients are followed up periodically for 10 years.
I. To evaluate the pathological complete response rate in patients with T3 and T4 rectal
cancers when treated preoperatively with capecitabine, oxaliplatin, bevacizumab, and
concurrent radiotherapy (XRT).
II. To evaluate the resection rate for T3 and T4 rectal cancers and the expected versus
actual type of resection (abdominoperinal resection [APR] vs. low anterior resection [LAR]
vs. LAR/coloanal anastomosis).
III. To make preliminary observations of patient survival and patterns of recurrence for this
treatment combination.
IV. To gain additional experience regarding the toxicity and tolerability of this
preoperative and postoperative regimen.
OUTLINE:
PREOPERATIVE CHEMORADIOTHERAPY: Patients undergo radiotherapy (total dose to the tumor bed
was 5040 cGy) once daily (QD) 5 days a week and receive capecitabine 825 mg/m^2 orally (PO)
twice daily (BID) 5 days a week for 5.5 weeks. Patients also receive oxaliplatin 50 mg/m^2
intravenously (IV) over 2 hours on days 1, 8, 15, 22, and 29 and bevacizumab 5 mg/kg IV over
30-90 minutes on days 1, 15, and 29 during radiotherapy.
SURGERY: Approximately 6-8 weeks after completion of chemoradiotherapy, patients undergo
surgical resection. Patients whose tumors are not completely resected or who have metastatic
disease discontinue protocol therapy.
POSTOPERATIVE CHEMOTHERAPY: Approximately 4-12 weeks after surgery, patients receive
oxaliplatin IV over 2 hours, leucovorin calcium 400 mg/m^2 IV over 2 hours, and bevacizumab 5
mg/kg IV over 30-90 minutes on day 1. Patients also receive fluorouracil 2400 mg/m^2 IV
continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 9 courses
in the absence of disease progression or unacceptable toxicity. Patients then receive up to 3
additional courses of leucovorin calcium, fluorouracil, and bevacizumab.
After completion of study treatment, patients are followed up periodically for 10 years.
Inclusion Criteria:
- Patients must have histologically confirmed, locally advanced, non-metastatic primary
T3 or T4 adenocarcinoma of the rectum
- Patients must not have evidence of tumor outside of the pelvis including liver
metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
- Patients must not have intra-operative radiotherapy (IORT) or brachytherapy treatment
to the pelvis
- The distal border of the tumor must be at or below the peritoneal reflection, defined
as within 12 centimeters of the anal verge by proctoscopic examination
- Transmural penetration of tumor through the muscularis propria must be demonstrated by
either of the following: computed tomography (CT) scan plus endorectal ultrasound, or
a magnetic resonance imaging (MRI); an endorectal coil or pelvic MRI is allowed
- For the patient to be eligible, the surgeon must prospectively define the tumor as
either initially resectable or potentially resectable after pre-operative
chemoradiation; clinically resectable tumors are defined as completely resectable with
negative margins based on routine examination of the non-anesthetized patient;
patients whose tumors are not resectable are not eligible; before pre-operative (op)
treatment, the surgeon should estimate and record the type of resection anticipated:
pelvic exenteration, posterior pelvic exenteration, APR, LAR, or LAR/coloanal
anastomosis
- Patients with tumors that are clinically fixed, clinical stage T4N0-2, M0 are eligible
if it is believed that their tumors are potentially resectable after chemoradiation;
based on the following:
- Clinically fixed tumors on rectal examination with tumor adherent to the pelvic
sidewall or sacrum
- Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the lack
of clear tissue plane will be considered evidence of fixation
- Hydronephrosis on CT scan or intravenous pyelogram (IVP) or ureteric or bladder
invasion as documented by cystoscopy and cytology or biopsy, or invasion into
prostate
- Vaginal or uterine involvement
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- A surgical evaluation must confirm patient's ability to tolerate the proposed surgical
procedure
- Patients must have a caloric intake > 1500 kilocalories/day (d)
- Within 4 weeks prior to registration, the patient's absolute neutrophil count (ANC)
level must be >= 1,500/mm^3
- Within 4 weeks prior to registration, the patients platelet level must be >=
100,000/mm^3
- Within 4 weeks prior to registration, serum creatinine must be < 1.5 X upper limit of
normal (ULN); if serum creatinine > 1.5 x ULN, then creatinine clearance must be >= 50
mL/mm
- Within 4 weeks prior to registration, serum bilirubin must be =< 1.5 X ULN
- Within 4 weeks prior to registration, alkaline phosphatase (alk phos) must be < 2 x
ULN
- Within 4 weeks prior to registration, serum glutamic oxaloacetic transaminase (SGOT)
must be < 2 x ULN
- Carcinoembryonic antigen (CEA) must be determined prior to initiation of therapy
- Within 4 weeks prior to registration, urine protein/creatinine (UPC) ratio must be <
1; patients with a ratio of >= 1 must undergo a 24-hour urine collection which must be
an adequate collection and must demonstrate < 1 gram (gm) of protein in order to
participate
- Within 4 weeks prior to registration, albumin must be >= 2 gm/dl
- Absence of clinical evidence of high-grade (lumen diameter < 1 cm) large bowel
obstruction, unless diverting colostomy has been performed
- Eligible patients of reproductive potential (both sexes) must agree to use an accepted
and effective method of contraceptive during study therapy and for at least 6 months
after the completion of bevacizumab
- Women must not be pregnant or breast-feeding; all females of childbearing potential
must have a serum pregnancy test to rule out pregnancy within 2 weeks of registration
- Patients must have had no prior chemotherapy for rectal cancer or pelvic irradiation
therapy
- Patients with prior malignancies, including pelvic cancer, are eligible if they have
been disease free for > 5 years; patients with prior in situ carcinomas are eligible
provided there was complete removal
- Patients must have no active inflammatory bowel disease or other serious medical
illness or disease that might limit the patient's ability to receive protocol therapy
- Patients with a history of cerebrovascular accident (CVA)/transient ischemic attack
(TIA) at any time, or myocardial infarction/unstable angina within 12 months of study
entry are not eligible
- Patients with > grade 1 peripheral neuropathy are not eligible
- Patients must have urine protein/creatinine (UPC) ratio of < 1.0; patients with a UPC
ratio >= 1.0 must undergo a 24-hour urine collection, which must be an adequate
collection and must demonstrate < 1 gm of protein in order to participate
- Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable
regimen of anti-hypertensive therapy
- Patients with clinically significant peripheral vascular disease are not eligible
- Patients must not have any of the following:
- Unstable angina (within 12 months of study entry)
- New York Heart Association (NYHA) grade II or higher congestive heart failure
- Evidence of bleeding diathesis/coagulopathy
- Serious non-healing wound or bone fracture
- Patients with a history of the following within 28 days prior to registration are not
eligible:
- Abdominal fistula
- Gastrointestinal perforation
- Intrabdominal abscess
- Patients with a history of the following within 28 days prior to day 0 (first
treatment day) are not eligible:
- Major surgical procedure
- Open biopsy
- Significant traumatic injury
- Patients must not have core biopsy within 7 days prior to day 0 (first treatment day)
- Patients with prothrombin time (PT) (international normalized ratio [INR]) > 1.5 are
not eligible, unless the patient is on full-dose anticoagulants; if so, the following
criteria must be met for enrollment:
- The subject must have an in-range INR (usually between 2 and 3), be on a stable
dose of warfarin or on a stable dose of low molecular weight heparin
- The subject must not have active bleeding or a pathological condition that is
associated with a high risk of bleeding
We found this trial at
107
sites
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Fairview Ridges Hospital Fairview Ridges Hospital is a 150-bed, Level III Trauma Care facility, offering...
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Hematology and Oncology Associates Northwestern Medical Faculty Foundation (the Foundation) is a premier, multi-specialty physician...
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Adena Regional Medical Center Since 1895, Adena Health System has remained focused on its commitment...
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Grant Medical Center Founded in 1900 in Columbus' downtown, Grant has grown into one of...
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Mercy Hospital Mercy Hospital, located in Coon Rapids, Minnesota, is a 271-bed non-profit hospital that...
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Grady Memorial Hospital As the center of healthcare in Delaware County, Grady Memorial Hospital is...
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Fairview Southdale Hospital Fairview Health Services is an award-winning nonprofit health care system based in...
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Unity Hospital Unity Hospital is one of the Twin Cities
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Borgess Medical Center At Borgess, healing is our calling. This is the place where people...
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Fairfield Medical Center We are people you know offering care you trust. Serving more than...
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Saint John's Hospital - Healtheast St. John's Hospital is committed to providing superior health care...
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Marietta Memorial Hospital We are 2,600 strong and the county
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9200 W Wisconsin Ave
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
(414) 805-3666
Froedtert and the Medical College of Wisconsin Froedtert Health combines with the Medical College of...
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Abbott Northwestern Hospital Our hospital has a long and proud history as a health care...
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The Hospital of Central Connecticut The Hospital of Central Connecticut is dedicated to fostering, sustaining...
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Licking Memorial Hospital Licking Memorial Health Systems (LMHS) is a not-for-profit health care organization dedicated...
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Alegent Health Bergan Mercy Medical Center Alegent Creighton Health is now CHI Health, giving you...
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Creighton University Medical Center St. Joseph's Mercy Hospital was founded on September 25, 1870 at...
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Thomas Jefferson University Hospital Our hospitals in Center City Philadelphia share a 13-acre campus with...
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3850 Park Nicollet Blvd
Saint Louis Park, Minnesota 55416
Saint Louis Park, Minnesota 55416
(952) 993-3123
Park Nicollet Clinic - Saint Louis Park Park Nicollet Health Services is a nonprofit, integrated...
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Regions Hospital Established in 1872, Regions Hospital is a private, not-for-profit organization. The hospital provides...
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Saint Francis Regional Medical Center St. Francis Regional Medical Center has a rich tradition of...
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Mercy Medical Center - Sioux City Living the traditions, visions and values of the Sisters...
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1305 W 18th St
Sioux Falls, South Dakota 57117
Sioux Falls, South Dakota 57117
(605) 333-1000
Sanford USD Medical Center - Sioux Falls Sanford
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Sioux Falls, South Dakota 57104
Sioux Falls, South Dakota 57104
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Hematology Oncology Associates of Illinois At Hematology Oncology Associates of Illinois, our goal is to...
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Springfield Regional Medical Center When it comes to your family
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Carle Cancer Center Carle Cancer Center delivers comprehensive care through leading-edge technology and advanced research,...
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