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Study Summary
No. 2007-0080:.......Rectum......Prajnan Das......Radiation Oncology
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Study Summary Title
Study Summary
Number:
2007-0080
Study Title:Phase I/II Trial of Preoperative Radiotherapy with Concurrent Bevacizumab, Erlotinib and Capecitabine for Locally Advanced Rectal cancer
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Physician New Patient Referral
Name:Prajnan DasPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Radiation OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-563-2300
Contact us about clinical trials
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General Information
Disease Group:RectumSupported By:Genentech
Phase of Study:Phase I/Phase IIReturn
Visit:
After completion of optional adjuvant chemotherapy, every 3-4 months for 2 yrs,
then every 6 months for the next 3 yrs
Treatment
Agents:
Bevacizumab
Capecitabine
Erlotinib
Home Care:n/a
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
n/a
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of bevacizumab (Avastin) and erlotinib hydrochloride (Tarceva) that can be
given in combination with standard radiation therapy and capecitabine before
surgery to patients with rectal cancer. The safety and effectiveness of this
combination of therapies will also be studied.
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Study Objectives / Outcomes
Primary
To determine the maximal tolerated dose (MTD) and potential dose-limiting toxicities of the combination of bevacizumab, erlotinib and capecitabine-based preoperative chemoradiation in patients with stage II and III (T3-4 and/or node-positive) rectal cancer.

Secondary
Ÿ To evaluate the rate of pathologic complete response in patients treated with preoperative radiation therapy with concurrent bevacizumab, erlotinib and capecitabine

Ÿ To evaluate the rates of local control, disease-free and overall survival in patients treated with preoperative radiation therapy with concurrent bevacizumab, erlotinib and capecitabine
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Study Status Information
Study Activation / Registration Date:12/19/2007
IRB Review and Approval Date:12/19/2007
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:N/A
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) ECOG performance status of 0 or 1.

2) Patients must be >/= 18 years of age.

3) All patients must have histologically confirmed adenocarcinoma of the rectum with pathologic material reviewed by the Department of Pathology at MDACC.

4) Patients must have clinical stage II-III (T3, T4 or node-positive) based on CT, MR or endoscopic ultrasound criteria.

5) Patients must have no distant metastatic disease on chest, abdomen and pelvic CT scan performed with IV contrast. If the CT was performed outside of MDACC, the slice thickness must be </= 7.5 mm. Criteria for pathologic enlargement of lymph nodes is > 15 mm on short axis dimension.

6) The rectal tumor must be either palpable on digital rectal exam or the inferior edge of the tumor must be within 12 cm of the anal verge based on rigid proctoscopy.

7) Patients must have ANC >/= 1500/L, platelets >/= 100,000/mm^3, total serum bilirubin less than 2.0 mg%, BUN </= 30 mg%, creatinine </= 1.5 mg% and creatinine clearance >/= 30ml/min (estimated as calculated with Cockcroft-Gault equation). Note: In patients with moderate renal impairment (estimated creatinine clearance 30-50 mL/min) at baseline, a dose reduction to 75% of the capecitabine starting dose is recommended.

8) Hemoglobin >/= 9 gm/dL (may be transfused to maintain or exceed this level).

9) Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary. Patients must be made aware of their other treatment options.

Exclusion Criteria:1) Prior radiotherapy to the pelvis.

2) Any prior chemotherapy.

3) Prior VEGF or EGFR-directed therapy, such as bevacizumab, cetuximab, erlotinib, or gefitinib.

4) Current, prior or planned participation in any other experimental drug study.

5) Pregnant or lactating woman. Woman of childbearing potential with either a positive or no pregnancy test at baseline. Women / men of childbearing potential not using a reliable contraceptive method (oral contraceptve, other hormonal contraceptive, intrauterine device, diaphragm or condom). (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 30 days from the date of the last study drug administration.

6) Serious, uncontrolled, concurrent infection(s) requiring IV antibiotics.

7) Treatment for other clinically significant cancers within the last five years, except cured non-melanoma skin cancer and treated in-situ cervical cancer.

8) Inadequately controlled hypertension [systolic blood pressure of >130 and/or diastolic blood pressure of >90 mmHg on antihypertensive medication at time of study entry and/or at time of starting therapy] history of myocardial infarction or unstable angina within 12 months prior to study enrollment, New York Heart Association Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible) or Class II or greater peripheral vascular disease

9) History of stroke or transient ischemic attack at any time,history of hypertensive crisis or hypertensive encephalopathy.

10) AST or ALT >/= 2.5 times the upper limit of normal.

11) Inability to swallow oral medication.

12) Evidence of bleeding diathesis or coagulopathy, INR >/= 2.5.

13) Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0.

14) Proteinuria at baseline or clinically significant impairment of renal function as demonstrated by either a. Urine protein:creatinine ratio >/= 1.0 at screening. b. Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).

15) Current serious, nonhealing wound, ulcer, or bone fracture.

16) History of aortic aneurysm > 4.5 or aortic dissection.

17) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.

18) Patients who have had an organ allograft.

19) Patients on Coumadin are recommended to be changed to Low Molecular Weight Heparin (LMWH) at least 1 week prior to starting capecitabine. If patients cannot be switched to LMWH, then extra monitoring of their International Normalized Ratio (INR) will be performed.

20) Patients taking Sorivudine or Brivudine must be off of these drugs for 4 weeks. Patients taking cimetidine must have this drug discontinued. Ranitidine or a drug from another anti-ulcer class can be substituted for cimetidine if necessary. If patient is currently receiving allopurinol, must discuss with PI to see of another agent may substitute for it.

21) Patients with known Gilberts disease will be considered ineligible due to potential UGTA1 polymorphism effects on metabolism for erlotinib.

22) Inability to comply with study and/or follow-up procedures.

23) Known hypersensitivity to any component of bevacizumab, erlotinib or capecitabine

24) Prior history of hypertensive crisis or hypertensive encephalopathy

25) Peripheral arterial thrombosis within 6 months prior to study enrollment

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Links
Registration Number: NCT00543842
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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