Rectal CancerPhase 2NCT00113230
Neoadjuvant Chemoradiation With RHUMAB VEGF (Avastin) for Rectal Cancer
A Phase 2 study testing Avastin (Bevacizumab, RHUMAB VEGF), Capecitabine and Radiation Therapy in people with Rectal Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Preoperative chemoradiation leads to increased pelvic control and overall survival, but both distant and local disease control remain problematic in locally advanced rectal cancer patients. Enhancing the effect of chemotherapy and radiotherapy can increase tumor response as well as distant disease control. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Avastin (Bevacizumab, RHUMAB VEGF), Capecitabine and Radiation Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2005to Jan 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ECOG status of 0 or 1.
- Patients must be greater than or equal to 18 years of age.
- All patients must have histologically confirmed adenocarcinoma of the rectum with pathologic material reviewed by the Department of Pathology at MDACC. The clinical stage must be T3, T4, or recurrent based on CT, MRI or EUS criteria.
- All patients must have no distant metastatic disease on abdominopelvic CT scan performed with IV contrast. If the CT was performed outside of MDACC, the slice thickness is 7.5 mm. Criteria for pathologic enlargement of lymph nodes is > 15 mm on short axis dimension. If CT findings of lung, liver, or peritoneal metastases are equivocal, patients are eligible to participate.
- 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.
- Patients must have WBC > 4000 cells/mm3, ANC of >1500/L, platelets > 100,000/mm3, total serum bilirubin < 2.0 mg%, BUN < 30 mg%, creatinine < 1.5 mg% and/or 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.
- Hemoglobin of >9 gm/dL (may be transfused or receive Procrit to maintain or exceed this level)
- 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.
Who cannot join
- Known compromised renal or hepatic function.
- Participation in any other experimental drug study.
- AST or ALT >5 times upper limit of normal for subjects with documented liver metastases; >2.5 times the upper limit of normal for subjects without evidence of liver metastases.
- Pregnant or lactating woman. Woman of childbearing potential with either a positive or no pregnancy test at baseline. Woman / men of childbearing potential not using a reliable contraceptive method. (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.
- Any prior chemotherapy.
- Any prior radiation therapy.
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- Serious, uncontrolled, concurrent infection(s) requiring IV antibiotics.
- Treatment for other carcinomas within the last five years, except cure non-melanoma skin cancer and treated in-situ cervical cancer.
- Clinically significant cardiac disease (e.g., uncontrolled hypertension [blood pressure of >160/110 mmHg on medication], any history of myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix H), unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or grade II or greater peripheral vascular disease(see Appendix H).
- Inability to to swallow oral medication.
- Evidence of bleeding diathesis or coagulopathy, INR greater than or equal to 1.5.
- 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.
- Proteinuria at baseline or clinically significant impairment of renal function Subjects unexpectedly discovered to have 1+ proteinuria at baseline should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate <500 mg of protein/24 hr to allow participation in the study (see appendix F).
- Currently has serious, nonhealing wound, ulcer, or bone fracture.
- Had aneurysms, strokes, transient ischemic attacks, and arteriovenous malformations within the past year.
- Patients who have had an organ allograft.
- Patients on Coumadin must be changed to Lovenox at least 1 week prior to starting capecitabine. Low dose (1 mg) Coumadin is allowed.
- Patients taking Sorivudine or Brivudine A 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UT M. D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase II Trial Of Neoadjuvant Concurrent Capecitabine, RHUMAB VEGF (Avastin) And Radiotherapy In Patients Presenting With Locally Advanced Rectal Cancer
Preoperative chemoradiation leads to increased pelvic control and overall survival, but both distant and local disease control remain problematic in locally advanced rectal cancer patients. Enhancing the effect of chemotherapy and radiotherapy can increase tumor response as well as distant disease control. Patients who have complete response to therapy have increased sphincter preservation, and can possibly have more limited surgery (full thickness local excision). When combined with standard chemotherapy, bevacizumab [RHUMAB VEGF, Avastin] has been shown to improve response and median survival in patients with metastatic colorectal cancer in a recent randomized trial, has led to increased activity in preclinical studies with radiotherapy, and has been found to be very well tolerated with chemoradiation in a phase I trial conducted at the M.D. Anderson Cancer Center (MDACC) in patients with locally advanced pancreatic cancer. The hypothesis is that the addition of bevacizumab to standard chemoradiation will safely lead to increased tumor response in patients with locally advanced rectal cancer.
Read the detailed description
Avastin [RHUMAB VEGF, Bevacizumab] is a drug that has damaging effects on blood vessel growth in tumors.
Before treatment starts, you will have a complete physical exam. About 2 tablespoons of blood will be drawn for routine tests and a urine test will be performed. Chest x-rays and CT scans of the abdomen and pelvis will be done. Women who are able to have children must have a negative blood pregnancy test.
You will receive radiation therapy once a day for 5 days in a row (Monday-Friday) for 5 weeks and three days (a total of 28 treatments). You will take the chemotherapy drug capecitabine by mouth twice a day on each of the days that you receive radiation therapy. These pills will not be taken on Saturday and Sunday. You must not take cimetidine, and must be off of coumadin for at least one week and sorivudine and brivudine for at least four weeks before starting capecitabine and while taking capecitabine.
You will receive the drug Avastin by vein once every 2 weeks for six weeks (a total of three doses). The infusion will at first last 90 minutes. If there are no allergic reactions, fevers or chills, it will be shortened to 60 minutes and then 30 minutes for later infusions.
During the study, you will have physical exams, including weekly blood tests (about 2 teaspoons). The possible development of side effects will be closely monitored.
All participants will have surgical removal of the rectal tumor 6-8 weeks after the completion of treatment as they would for the standard of care for their disease. No patients will have surgery before 6 weeks.
After participation in this study is over, you will have follow-up evaluation as needed for standard of care.
THIS IS AN INVESTIGATIONAL STUDY. Capecitabine is approved by the FDA, but Avastin has not yet been evaluated for approval.
About 50 patients will take part in the study. All will be enrolled at the M. D. Anderson.
- Conditions
- Rectal Cancer
- Being tested
- Avastin (Bevacizumab, RHUMAB VEGF), Capecitabine, Radiation Therapy
- Keywords
- Rectal Cancer, Bevacizumab, RHUMAB VEGF, Avastin, Capecitabine, Neoadjuvant Concurrent Capecitabine, Xeloda, Radiation, Radiotherapy, Radiation Therapy, XRT
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avastin (Bevacizumab, RHUMAB VEGF)Drug
Also called RHUMAB VEGF, Avastin, Bevacizumab
Starting Dose 5 mg/kg intravenously on day one of radiotherapy, given every 2 weeks +/- 2 days for a total of 3 doses.
CapecitabineDrug
Also called Xeloda
900 mg/m^2 by mouth twice a day during days of radiation for all five weeks of therapy.
Radiation TherapyRadiation
Also called XRT, Radiotherapy
45 Gy in 25 fractions to the pelvis followed by 5.4 Gy as a boost dose to the primary tumor with margin, for a total dose of 50.4 Gy over 28 treatment days.
| Study group | Role | What they receive |
|---|---|---|
| Avastin | Experimental | Capecitabine, Avastin (RHUMAB VEGF/Bevacizumab) And Radiotherapy Receives: Drug: Avastin (Bevacizumab, RHUMAB VEGF); Drug: Capecitabine; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Local Tumor Response
At follow-up evaluation after completion of neoadjuvant and surgical therapy, resected primary tumor classified based on routine pathology staining in the following manner: Pathologic Complete Response (no evidence of residual cancer); Microscopic Residual (no grossly detected disease, but evidence of microscopic residual disease); and Gross Residual Disease.
Measured: Baseline to approximately 5 Months (Following 28 days of treatment, chemotherapy and surgical resection of tumor)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2005 (estimated)
- Study startFeb 2005
- Primary completionJan 2009
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Christopher H. Crane, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00113230
- Sponsor's protocol ID
- 2003-0832
- Status last verified
- Jul 2012
- First submitted
- 6 Jun 2005
- Last updated
- 7 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Of Neoadjuvant Concurrent Capecitabine, RHUMAB VEGF (Avastin) And Radiotherapy In Patients Presenting With Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT00113230
- Acronym / sponsor ID
- 2003-0832
- Conditions
- Rectal Cancer
- Keywords
- Rectal Cancer, Bevacizumab, RHUMAB VEGF, Avastin, Capecitabine, Neoadjuvant Concurrent Capecitabine, Xeloda, Radiation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Feb 2005
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 7 Jun 2005 (estimated)
- Results
- Posted 13 Nov 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preoperative chemoradiation leads to increased pelvic control and overall survival, but both distant and local disease control remain problematic in locally advanced rectal cancer patients. Enhancing the effect of chemotherapy and radiotherapy can increase tumor response as well as distant disease control. Patients who have complete response to therapy have increased sphincter preservation, and can possibly have more limited surgery (full thickness local excision). When combined with standard chemotherapy, bevacizumab [RHUMAB VEGF, Avastin] has been shown to improve response and median survival in patients with metastatic colorectal cancer in a recent randomized trial, has led to increased activity in preclinical studies with radiotherapy, and has been found to be very well tolerated with chemoradiation in a phase I trial conducted at the M.D. Anderson Cancer Center (MDACC) in patients with locally advanced pancreatic cancer. The hypothesis is that the addition of bevacizumab to standard chemoradiation will safely lead to increased tumor response in patients with locally advanced rectal cancer.
Detailed description
Avastin [RHUMAB VEGF, Bevacizumab] is a drug that has damaging effects on blood vessel growth in tumors.
Before treatment starts, you will have a complete physical exam. About 2 tablespoons of blood will be drawn for routine tests and a urine test will be performed. Chest x-rays and CT scans of the abdomen and pelvis will be done. Women who are able to have children must have a negative blood pregnancy test.
You will receive radiation therapy once a day for 5 days in a row (Monday-Friday) for 5 weeks and three days (a total of 28 treatments). You will take the chemotherapy drug capecitabine by mouth twice a day on each of the days that you receive radiation therapy. These pills will not be taken on Saturday and Sunday. You must not take cimetidine, and must be off of coumadin for at least one week and sorivudine and brivudine for at least four weeks before starting capecitabine and while taking capecitabine.
You will receive the drug Avastin by vein once every 2 weeks for six weeks (a total of three doses). The infusion will at first last 90 minutes. If there are no allergic reactions, fevers or chills, it will be shortened to 60 minutes and then 30 minutes for later infusions.
During the study, you will have physical exams, including weekly blood tests (about 2 teaspoons). The possible development of side effects will be closely monitored.
All participants will have surgical removal of the rectal tumor 6-8 weeks after the completion of treatment as they would for the standard of care for their disease. No patients will have surgery before 6 weeks.
After participation in this study is over, you will have follow-up evaluation as needed for standard of care.
THIS IS AN INVESTIGATIONAL STUDY. Capecitabine is approved by the FDA, but Avastin has not yet been evaluated for approval.
About 50 patients will take part in the study. All will be enrolled at the M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avastin | Experimental | Drug: Avastin (Bevacizumab, RHUMAB VEGF), Drug: Capecitabine, Radiation: Radiation TherapyCapecitabine, Avastin (RHUMAB VEGF/Bevacizumab) And Radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- ECOG status of 0 or 1.
- Patients must be greater than or equal to 18 years of age.
- All patients must have histologically confirmed adenocarcinoma of the rectum with pathologic material reviewed by the Department of Pathology at MDACC. The clinical stage must be T3, T4, or recurrent based on CT, MRI or EUS criteria.
- All patients must have no distant metastatic disease on abdominopelvic CT scan performed with IV contrast. If the CT was performed outside of MDACC, the slice thickness is 7.5 mm. Criteria for pathologic enlargement of lymph nodes is > 15 mm on short axis dimension. If CT findings of lung, liver, or peritoneal metastases are equivocal, patients are eligible to participate.
- 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.
Key exclusion criteria (18 listed)
- Known compromised renal or hepatic function.
- Participation in any other experimental drug study.
- AST or ALT >5 times upper limit of normal for subjects with documented liver metastases; >2.5 times the upper limit of normal for subjects without evidence of liver metastases.
- Pregnant or lactating woman. Woman of childbearing potential with either a positive or no pregnancy test at baseline. Woman / men of childbearing potential not using a reliable contraceptive method. (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.
- Any prior chemotherapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Avastin (Bevacizumab, RHUMAB VEGF)Also: RHUMAB VEGF, Avastin, BevacizumabStarting Dose 5 mg/kg intravenously on day one of radiotherapy, given every 2 weeks +/- 2 days for a total of 3 doses. | Drug | Avastin |
| CapecitabineAlso: Xeloda900 mg/m^2 by mouth twice a day during days of radiation for all five weeks of therapy. | Drug | Avastin |
| Radiation TherapyAlso: XRT, Radiotherapy45 Gy in 25 fractions to the pelvis followed by 5.4 Gy as a boost dose to the primary tumor with margin, for a total dose of 50.4 Gy over 28 treatment days. | Radiation | Avastin |
Primary outcome
Pathologic Local Tumor Response
Time frame: Baseline to approximately 5 Months (Following 28 days of treatment, chemotherapy and surgical resection of tumor)
At follow-up evaluation after completion of neoadjuvant and surgical therapy, resected primary tumor classified based on routine pathology staining in the following manner: Pathologic Complete Response (no evidence of residual cancer); Microscopic Residual (no grossly detected disease, but evidence of microscopic residual disease); and Gross Residual Disease.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The University of Texas M.D.Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher H. Crane, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avastin (Bevacizumab, RHUMAB VEGF), Capecitabine and Radiation Therapy in people with Rectal Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Local Tumor Response (time frame: Baseline to approximately 5 Months (Following 28 days of treatment, chemotherapy and surgical resection of tumor)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2012.