Rectal CancerPhase 2NCT00308516
5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer
A Phase 2 study testing 5-Fluorouracil, Bevacizumab and Radiation Therapy in people with Rectal Cancer and Cancer of the Rectum, run by SCRI Development Innovations, LLC at 14 sites in United States.
Trial summary
This phase II trial will investigate the combination of adjuvant 5-fluorouracil, radiation, and bevacizumab in patients with stage II and III rectal cancer, followed by FOLFOX6 and bevacizumab. Fluorouracil (FU) has proven to be an effective and safe regimen in the treatment of stage II and III rectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer, Cancer of the Rectum, Colorectal Cancer
- What is being tested?
- 5-Fluorouracil, Bevacizumab and Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 14 sitesUnited States
- Study dates
- Mar 2006to Feb 2012
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed Stage I or II rectal cancer
- Patients must be candidates for preoperative or adjuvant chemoradiation.
- Patients enrolling in the adjuvant chemoradiation cohort must have undergone surgical resection of the primary rectal tumor between 28 and 56 days (i.e., 4-8 weeks) prior to study treatment.
- ECOG performance status 0-1
- Adequate bone marrow, liver, and kidney function
- At least 18 years of age
- Able to give written informed consent
Who cannot join
- Treatment with prior chemotherapy or radiation for rectal cancer
- History of myocardial infarction
- Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication or peripheral vascular disease
- History of stroke within 6 months
- History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months
- Symptomatic sensory or peripheral neuropathy
Show all 19Show fewer
- Prior treatment with anti-angiogenic agents
- Prior malignancy in the past 5 years
- Active infections or serious underlying medical condition
- Major surgery less than 28 days prior
- Women who are pregnant or lactating
- Thrombolytic therapy within 10 days of starting bevacizumab
- PEG tube, G-tube, or external biliary stents
- Proteinuria
- Non healing wound, ulcer or fracture
- History of bleeding diathesis or coagulopathy
- Hemoptysis
- Participation in another experimental trial within 28 days
- Uncontrolled anticoagulant therapy
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Northeast Alabama Regional Medical Center
Anniston, Alabama, 36207
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, 37404
Consultants in Medical Oncology and Hematology
Drexel Hill, Pennsylvania, 19026
Florida Cancer Specialists
Fort Myers, Florida, 33901
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
Integrated Community Oncology Network
Jacksonville, Florida, 32256
Northeast Arkansas Clinic
Jonesboro, Arkansas, 72401
Watson Clinic Center for Cancer Care and Research
Lakeland, Florida, 33805
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, 40207
Wellstar Cancer Research
Marietta, Georgia, 30060
Tennessee Oncology
Nashville, Tennessee, 37205
Peninsula Cancer Institute
Newport News, Virginia, 23601
South Texas Oncology and Hematology
San Antonio, Texas, 78258
Spartanburg Regional Medical Center
Spartanburg, South Carolina, 29303
About this study
Official title: A Phase II Study of 5-Fluorouracil, Bevacizumab (Avastin), and Radiation in the Preoperative or Adjuvant Treatment of Patients With Stage II / III Rectal Cancer
This phase II trial will investigate the combination of adjuvant 5-fluorouracil, radiation, and bevacizumab in patients with stage II and III rectal cancer, followed by FOLFOX6 and bevacizumab. Fluorouracil (FU) has proven to be an effective and safe regimen in the treatment of stage II and III rectal cancer. Recent evidence has proven fluorouracil/leucovorin (FL) in combination with bevacizumab is superior to FL alone and when combined with irinotecan is superior to (irinotecan plus fluorouracil/leucovorin (IFL) alone. This trial will be one of the first clinical trials to evaluate a combination of targeted therapy, radiation, and chemotherapy in the adjuvant treatment of a common solid tumor.
Read the detailed description
All eligible patients will receive combined modality treatment initially. Systemic treatment will begin 4-6 weeks after completion of the Combined Modality portion and will complete 4 cycles of a 4 week regimen. Patients with no evidence of disease following systemic therapy may continue single agent bevacizumab for up to one year. After all treatment is completed, patients will be re-evaluated with imaging to establish a new baseline. Patients will be re-evaluated thereafter for up to a total of 5 years.
Combined Modality Treatment:
- bevacizumab 5mg/kg IV infusion days 1, 15, and 29
- fluorouracil 225mg/m2 IV continuous infusion days 1-42
- radiation 1.8 Gy/day or 28 fractions weeks 1-6
Systemic Treatment:
- 5-fluorouracil 400 mg/m2 bolus
- 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15
- leucovorin 350 mg prior to FU on days 1 and 15
- oxaliplatin 85 mg/m2 days 1 and 15
- bevacizumab 5 mg/kg days 1 and 15
- Conditions
- Rectal Cancer, Cancer of the Rectum, Colorectal Cancer
- Being tested
- 5-Fluorouracil, Bevacizumab, Radiation Therapy, Oxaliplatin, Leucovorin
- Keywords
- Rectal Cancer, Cancer of the Rectum, Colorectal Cancer, Bevacizumab
- Medical subject headings
- Rectal Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
Also called Fluorouracil, Efudex, 5-FU
Combined Modality Treatment:
fluorouracil 225mg/m2 IV continuous infusion days 1-42
Systemic Treatment:
5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15
BevacizumabDrug
Also called Avastin
Combined Modality Treatment:
bevacizumab 5mg/kg IV infusion days 1, 15, and 29
Systemic Treatment:
bevacizumab 5 mg/kg days 1 and 15
Radiation TherapyProcedure or surgery
radiation 1.8 Gy/day or 28 fractions weeks 1-6
OxaliplatinDrug
Also called Eloxatin
Systemic Treatment:
oxaliplatin 85 mg/m2 days 1 and 15
LeucovorinDrug
Also called Folinic acid
Systemic Treatment:
leucovorin 350 mg prior to FU on days 1 and 15
| Study group | Role | What they receive |
|---|---|---|
| Cohort A - Preoperative | Experimental | Each patient enrolled in the preoperative cohort received 5-fluorouracil (5-FU) 225 mg/m2 as a continuous infusion (IVCI) on days 1-42 through a portable infusion pump and central venous catheter. Bevacizumab 5 mg/kg was administered intravenously (IV) on days 1 and 15. Additionally these patients received radiation therapy to 50.4 Gy (1.8 Gy/day or 28 fractions) Monday through Friday during weeks 1-6.
At least 8 weeks after surgery, patients in cohort A began 4 months of chemotherapy and bevacizumab. This adjuvant treatment consisted of 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle. Receives: Drug: 5-Fluorouracil; Drug: Bevacizumab; Procedure: Radiation Therapy; Drug: Oxaliplatin; Drug: Leucovorin |
| Cohort B - Combined Modality | Experimental | All patients enrolled in cohort B received 5-fluorouracil (5-FU) 225 mg/m2 IVCI on days 1-42. Bevacizumab was administered at 5 mg/kg IV on day 1 every 2 weeks. These patients also received radiation to 50.4 Gy (1.8 Gy/day or 28 fractions)Monday through Friday during weeks 1-6.
Six weeks after the completion of adjuvant 5-FU/radiation, patients began treatment with 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle. Receives: Drug: 5-Fluorouracil; Drug: Bevacizumab; Procedure: Radiation Therapy; Drug: Oxaliplatin; Drug: Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
Measured: 24 months
Secondary outcomes (1)
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Overall Survival (OS) is defined ad the Length of time, in months, that patients were alive from their first date of protocol treatment until death.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2006 (estimated)
- Study startMar 2006
- Primary completionApr 2009
- Study completionFeb 2012
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- 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
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- David R. Spigel, MD, Principal investigator, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00308516
- Sponsor's protocol ID
- SCRI GI 65
- Other IDs
- AVF3105s
- Status last verified
- Nov 2021
- First submitted
- 28 Mar 2006
- Last updated
- 10 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Spigel DR, Bendell JC, McCleod M, Shipley DL, Arrowsmith E, Barnes EK, Infante JR, Burris HA 3rd, Greco FA, Hainsworth JD. Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer. Clin Colorectal Cancer. 2012 Mar;11(1):45-52. doi: 10.1016/j.clcc.2011.04.002. Epub 2011 Aug 15.
PubMed 21840771
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of 5-Fluorouracil, Bevacizumab (Avastin), and Radiation in the Preoperative or Adjuvant Treatment of Patients With Stage II / III Rectal Cancer
- ClinicalTrials.gov ID
- NCT00308516
- Acronym / sponsor ID
- SCRI GI 65
- Conditions
- Rectal Cancer, Cancer of the Rectum, Colorectal Cancer
- Keywords
- Rectal Cancer, Cancer of the Rectum, Colorectal Cancer, Bevacizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Mar 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 29 Mar 2006 (estimated)
- Results
- Posted 14 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial will investigate the combination of adjuvant 5-fluorouracil, radiation, and bevacizumab in patients with stage II and III rectal cancer, followed by FOLFOX6 and bevacizumab. Fluorouracil (FU) has proven to be an effective and safe regimen in the treatment of stage II and III rectal cancer. Recent evidence has proven fluorouracil/leucovorin (FL) in combination with bevacizumab is superior to FL alone and when combined with irinotecan is superior to (irinotecan plus fluorouracil/leucovorin (IFL) alone. This trial will be one of the first clinical trials to evaluate a combination of targeted therapy, radiation, and chemotherapy in the adjuvant treatment of a common solid tumor.
Detailed description
All eligible patients will receive combined modality treatment initially. Systemic treatment will begin 4-6 weeks after completion of the Combined Modality portion and will complete 4 cycles of a 4 week regimen. Patients with no evidence of disease following systemic therapy may continue single agent bevacizumab for up to one year. After all treatment is completed, patients will be re-evaluated with imaging to establish a new baseline. Patients will be re-evaluated thereafter for up to a total of 5 years.
Combined Modality Treatment:
- bevacizumab 5mg/kg IV infusion days 1, 15, and 29
- fluorouracil 225mg/m2 IV continuous infusion days 1-42
- radiation 1.8 Gy/day or 28 fractions weeks 1-6
Systemic Treatment:
- 5-fluorouracil 400 mg/m2 bolus
- 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15
- leucovorin 350 mg prior to FU on days 1 and 15
- oxaliplatin 85 mg/m2 days 1 and 15
- bevacizumab 5 mg/kg days 1 and 15
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A - Preoperative | Experimental | Drug: 5-Fluorouracil, Drug: Bevacizumab, Procedure: Radiation Therapy, Drug: Oxaliplatin, Drug: LeucovorinEach patient enrolled in the preoperative cohort received 5-fluorouracil (5-FU) 225 mg/m2 as a continuous infusion (IVCI) on days 1-42 through a portable infusion pump and central venous catheter. Bevacizumab 5 mg/kg was administered intravenously (IV) on days 1 and 15. Additionally these patients received radiation therapy to 50.4 Gy (1.8 Gy/day or 28 fractions) Monday through Friday during weeks 1-6. At least 8 weeks after surgery, patients in cohort A began 4 months of chemotherapy and bevacizumab. This adjuvant treatment consisted of 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle. |
| Cohort B - Combined Modality | Experimental | Drug: 5-Fluorouracil, Drug: Bevacizumab, Procedure: Radiation Therapy, Drug: Oxaliplatin, Drug: LeucovorinAll patients enrolled in cohort B received 5-fluorouracil (5-FU) 225 mg/m2 IVCI on days 1-42. Bevacizumab was administered at 5 mg/kg IV on day 1 every 2 weeks. These patients also received radiation to 50.4 Gy (1.8 Gy/day or 28 fractions)Monday through Friday during weeks 1-6. Six weeks after the completion of adjuvant 5-FU/radiation, patients began treatment with 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically confirmed Stage I or II rectal cancer
- Patients must be candidates for preoperative or adjuvant chemoradiation.
- Patients enrolling in the adjuvant chemoradiation cohort must have undergone surgical resection of the primary rectal tumor between 28 and 56 days (i.e., 4-8 weeks) prior to study treatment.
- ECOG performance status 0-1
- Adequate bone marrow, liver, and kidney function
Key exclusion criteria (19 listed)
- Treatment with prior chemotherapy or radiation for rectal cancer
- History of myocardial infarction
- Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication or peripheral vascular disease
- History of stroke within 6 months
- History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months
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 |
|---|---|---|
| 5-FluorouracilAlso: Fluorouracil, Efudex, 5-FUCombined Modality Treatment: fluorouracil 225mg/m2 IV continuous infusion days 1-42 Systemic Treatment: 5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15 | Drug | Cohort A - Preoperative, Cohort B - Combined Modality |
| BevacizumabAlso: AvastinCombined Modality Treatment: bevacizumab 5mg/kg IV infusion days 1, 15, and 29 Systemic Treatment: bevacizumab 5 mg/kg days 1 and 15 | Drug | Cohort A - Preoperative, Cohort B - Combined Modality |
| Radiation Therapyradiation 1.8 Gy/day or 28 fractions weeks 1-6 | Procedure or surgery | Cohort A - Preoperative, Cohort B - Combined Modality |
| OxaliplatinAlso: EloxatinSystemic Treatment: oxaliplatin 85 mg/m2 days 1 and 15 | Drug | Cohort A - Preoperative, Cohort B - Combined Modality |
| LeucovorinAlso: Folinic acidSystemic Treatment: leucovorin 350 mg prior to FU on days 1 and 15 | Drug | Cohort A - Preoperative, Cohort B - Combined Modality |
Primary outcome
Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
Time frame: 24 months
The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
1 secondary outcome
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21840771Spigel DR, Bendell JC, McCleod M, Shipley DL, Arrowsmith E, Barnes EK, Infante JR, Burris HA 3rd, Greco FA, Hainsworth JD. Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer. Clin Colorectal Cancer. 2012 Mar;11(1):45-52. doi: 10.1016/j.clcc.2011.04.002. Epub 2011 Aug 15.
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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.
David R. Spigel, MD principal investigator
SCRI Development Innovations, LLC
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-Fluorouracil, Bevacizumab and Radiation Therapy in people with Rectal Cancer and Cancer of the Rectum, run by SCRI Development Innovations, LLC at 14 sites 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 7 inclusion and 19 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 10 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites 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 14 May 2013). 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?
Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00308516, which also lists 1 linked publication.
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 10 Dec 2021.