Bevacizumab, Radiation Therapy, and Combination Chemotherapy in Treating Patients Who Are Undergoing Surgery for Locally Advanced Nonmetastatic Rectal Cancer - NCT00321685-54601(Clinical Trial 141475)
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| City: |
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La Crosse |
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State:
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WI |
| Zip Code: |
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54601 |
| Conditions: |
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Colorectal Cancer |
| Purpose: |
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RATIONALE: 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.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with radiation
therapy and combination chemotherapy works in treating patients who are undergoing surgery
for locally advanced nonmetastatic rectal cancer.
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| Study summary: |
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OBJECTIVES:
Primary
- Evaluate the pathological complete response rate in patients with T3 or T4 rectal
cancer treated with neoadjuvant bevacizumab in combination with radiotherapy,
capecitabine, and oxaliplatin followed by surgical resection and adjuvant bevacizumab
in combination with fluorouracil, leucovorin calcium, and oxaliplatin.
Secondary
- Evaluate the resection rate for T3 and T4 rectal cancers.
- Evaluate the expected versus actual type of resection (abdominoperineal resection [APR]
vs low anterior resection [LAR] vs LAR/coloanal anastomosis) performed on these
patients.
- Determine, preliminarily, survival and patterns of recurrence in patients treated with
this regimen.
- Determine the toxicity and tolerability of this preoperative and postoperative regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to primary tumor
size (T3 vs T4).
- Preoperative chemoradiotherapy: Patients undergo radiotherapy once daily 5 days a week
and receive oral capecitabine twice daily 5 days a week for 5½ weeks. Patients also
receive oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29 and bevacizumab 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 4-8 weeks after surgery, patients receive
oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV
over 30-90 minutes on day 1. Patients also receive fluorouracil (5-FU) 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, 5-FU, and bevacizumab.
After completion of study treatment, patients are followed periodically for 10 years.
PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study. |
| Criteria: |
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DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the rectum
- Locally advanced disease
- Must have primary T3 or T4 tumor
- Transmural penetration of tumor through the muscularis propria by CT scan plus
endorectal ultrasound or MRI
- An endorectal coil or pelvic MRI is allowed
- Distal border of the tumor must be at or below the peritoneal reflection,
defined as within 12 cm of the anal verge by proctoscopic examination
- Tumors that are clinically fixed, clinical stage T4, N0-2, M0 are eligible if it
is believed that the tumors are potentially resectable after chemoradiotherapy,
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 or ureteric or bladder
invasion as documented by cystoscopy and cytology or biopsy, or invasion
into the prostate
- Vaginal or uterine involvement
- Nonmetastatic disease
- No evidence of tumor outside of the pelvis
- No liver metastases
- No peritoneal seeding
- No metastatic inguinal lymphadenopathy
- Resectable disease, defined as completely resectable disease with negative margins
based on routine examination of the non-anesthetized patient
- A surgeon must prospectively define the tumor as either initially resectable or
potentially resectable after preoperative chemoradiotherapy
- A surgical evaluation must confirm patient's ability to tolerate the proposed
surgical procedure
- Carcinoembryonic antigen must be determined prior to initiation of therapy
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine clearance ≥ 50 mL/min
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Alkaline phosphatase < 2 times ULN
- SGOT < 2 times ULN
- Urine protein:creatinine ratio < 1
- Patients with a urine protein:creatinine ratio of ≥ 1 must demonstrate < 1 gm of
protein by 24-hour urine collection
- INR ≤ 1.5 unless patient is on full-dose anticoagulants and the following criteria is
met:
- In range INR (usually between 2 and 3)
- On a stable dose of warfarin or on a stable dose of low molecular weight heparin
- Must not have active bleeding or a pathological condition that is associated
with a high risk of bleeding
- Caloric intake > 1,500 kilocalories/day
- Albumin > 2 gm/dL
- No known dihydropyrimidine dehydrogenase deficiency
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after
discontinuing bevacizumab
- No clinical evidence of high-grade (lumen diameter < 1 cm) large bowel obstruction,
unless diverting colostomy has been performed
- No active inflammatory bowel disease
- No history of cerebrovascular accident/transient ischemic attack
- No myocardial infarction or unstable angina within the past 12 months
- No peripheral neuropathy > grade 1
- No clinically significant peripheral vascular disease
- Patients with a history of hypertension must have a blood pressure of < 150/90 mm Hg
and be on a stable regimen of antihypertensive therapy
- No New York Heart Association class II-IV congestive heart failure
- No evidence of bleeding diathesis/coagulopathy
- No serious nonhealing wound or bone fracture
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days
- No significant traumatic injury within the past 28 days
- No other malignancy within the past 5 years except for in situ carcinomas that were
completely removed
- No known allergy to study drugs
- No other serious medical illness or disease that might limit the patient's ability to
receive protocol therapy
PRIOR CONCURRENT THERAPY:
- At least 28 days since prior major surgical procedure or open biopsy
- At least 7 days since prior core biopsy
- No prior chemotherapy for rectal cancer
- No prior pelvic irradiation
- No prior intra-operative radiotherapy (IORT) or brachytherapy treatment to the pelvis
- No concurrent intensity-modulated radiotherapy
- No concurrent full-dose anticoagulants |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 21, 2010 |
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