Bevacizumab, Erlotinib, and Capecitabine for Locally Advanced Rectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00543842
Recruitment Status : Completed
First Posted : October 15, 2007
Last Update Posted : February 26, 2015
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.

The goal of this Phase I trial was to determine the maximal tolerated dose (MTD) of concurrent capecitabine, bevacizumab and erlotinib with preoperative radiation therapy (RT) for rectal cancer. The trial completed as Phase I without progressing to the Phase II portion.

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: Bevacizumab Drug: Capecitabine Drug: Erlotinib Radiation: Radiation Therapy Procedure: Surgery Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Preoperative Radiotherapy With Concurrent Bevacizumab, Erlotinib and Capecitabine for Locally Advanced Rectal Cancer
Study Start Date : December 2007
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Bevacizumab + Erlotinib + Capecitabine + Radiation Therapy
Bevacizumab 5 mg/kg intravenous (IV) every 2 weeks for 3 Doses (Weeks 1, 3, 5). Erlotinib starting dose 50 mg orally daily Weeks 1-3. Capecitabine starting dose 650 mg/m^2 orally twice daily Monday-Friday for 6 Weeks. Radiation Therapy 30 minute radiation treatments, dose of 50.4 Gy once daily on 5 consecutive days, for up to 5 weeks and 3 days, totaling 28 treatments. At least 8 weeks after radiation therapy, surgical removal of rectal tumor.
Drug: Bevacizumab
5 mg/kg By Vein Every 2 Weeks x 3 Doses (Weeks 1, 3, 5)
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Drug: Capecitabine
Starting Dose 650 mg/m^2 By Mouth Twice Daily Monday-Friday x 6 Weeks
Other Name: Xeloda

Drug: Erlotinib
Starting Dose 50 mg By Mouth Daily Weeks 1-3
Other Names:
  • Erlotinib Hydrocloride
  • OSI-774
  • Tarceva

Radiation: Radiation Therapy
30 minute radiation treatments, dose of 50.4 Gy once daily on 5 consecutive days, for up to 5 weeks and 3 days, totaling 28 treatments
Other Names:
  • RT
  • XRT
  • Radiotherapy

Procedure: Surgery
At least 8 weeks after radiation therapy, surgical removal of rectal tumor

Primary Outcome Measures :
  1. Maximal tolerated dose (MTD) [ Time Frame: Continuoual Reassessment Weeks 1- 6 ]
    MTD derived from differing dose combinations of Capecitabine, Bevacizumab, and Erlotinib of using the continual reassessment method (CRM). Dose limiting toxicity defined as any grade 3 or higher acute toxicity during chemoradiation. The MTD will be defined as the dose at which grade 3 or higher acute toxicity exceeds 25%.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (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 MD Anderson Cancer Center (MDACC).
  4. Patients must have clinical stage II-III (T3, T4 or node-positive) based on computed tomography (CT), magnetic resonance (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 absolute neutrophil count (ANC) >/= 1500/L, platelets >/= 100,000/mm^3, total serum bilirubin less than 2.0 mg%, blood urea nitrogen (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 vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (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 contraceptive, 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 intravenous (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. Aspartate aminotransferase or alanine aminotransferase (AST or ALT) >/= 2.5 times the upper limit of normal.
  11. Inability to swallow oral medication.
  12. Evidence of bleeding diathesis or coagulopathy, international normalized ratio (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00543842

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech, Inc.
Principal Investigator: Prajnan Das, MD UT MD Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00543842     History of Changes
Other Study ID Numbers: 2007-0080
First Posted: October 15, 2007    Key Record Dates
Last Update Posted: February 26, 2015
Last Verified: February 2015

Keywords provided by M.D. Anderson Cancer Center:
Rectal Cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Erlotinib Hydrochloride
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors