Rectal CancerPhase 2NCT01749956
5-FU, Aflibercept, and Radiation (RT) for Preoperative and Postoperative Patients With Stage II/III Rectal Cancer
A Phase 2 study testing Radiation, Aflibercept and Surgery in people with Rectal Cancer, run by SCRI Development Innovations, LLC at 11 sites in United States.
Trial summary
The purpose of this Phase II study will be to investigate the antiangiogenic agent, aflibercept, in combination with chemoradiation as preoperative treatment for patients with stage II/III rectal cancer, followed by 4 months of FOLFOX6 plus aflibercept adjuvantly. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Radiation, Aflibercept and Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 11 sitesUnited States
- Study dates
- Jan 2013to Sep 2015
- 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
- Patients with histologically confirmed stage II or III rectal cancer (adenocarcinoma)
- Patients must be candidates for preoperative chemoradiation
- Male or female patients ≥18 years-of-age
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
- Adequate hematologic, liver and renal function
- Male patients willing to use adequate contraceptive measures
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- Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test <7 days prior to start of treatment
- Life expectancy ≥12 weeks
- Willingness and ability to comply with the trial and follow-up procedures
- Ability to understand the nature of this trial and give written informed consent.
Who cannot join
- Treatment with prior chemotherapy or radiation for rectal cancer.
- Patients who have received any other investigational agents within the 28 days prior to Day 1 of the study.
- Known to be human immunodeficiency virus positive or hepatitis B or C positive
- Women who are pregnant or breastfeeding
- History of acute myocardial infarction within the previous 6 months, uncontrolled hypertension (blood pressure >150/100 mmHg and/or diastolic blood pressure >100 mmHg), unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication (excluding atrial fibrillation), or ≥ Grade 2 peripheral vascular disease.
- History of hypertensive crisis or hypertensive encephalopathy.
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- History of stroke or transient ischemic attack within the past 6 months.
- Significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of therapy.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
- Patients with symptomatic sensory or peripheral neuropathy (Grade 2 or above).
- Patients may not have received other agents, either investigational or marketed, that act by primary anti-angiogenic mechanisms.
- Prior malignancy (except for adequately treated basal-cell or squamous-cell skin cancers, in situ carcinomas, or low grade [Gleason score of 3+3 or less] localized prostate cancer) in the past 5 years.
- Patients with active concurrent infections or patients with serious underlying medical conditions.
- Patients receiving full-dose oral or parenteral/SC anticoagulation must be on a stable dosing schedule prior to enrollment; a coumadin dose must be stable for 1 week. If this cannot be achieved, the patient will be ineligible for enrollment.
- Major surgical procedure or significant traumatic injury within 28 days prior to study initiation, or anticipation of need for major surgical procedure during the course of the study.
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of therapy.
- Patients with proteinuria, as demonstrated by a urine protein of 2+ or greater at screening. If 2+ or greater proteinuria, a 24-hour urine can be obtained, and if the result is <1 gm/24 hours, the patient is eligible.
- Any non-healing wound, ulcer, or bone fracture.
- Any clinical evidence or history of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- History of hemoptysis (≥½ teaspoon of bright red blood per episode) within 1 month prior to initiation of therapy.
- History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Tennessee Oncology - Chattanooga
Chattanooga, Tennessee, 37404
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45242
South Carolina Oncology Associates
Columbia, South Carolina, 29210
Florida Cancer Specialists
Fort Myers, Florida, 33916
Baptist Hospital East
Louisville, Kentucky, 40207
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Oklahoma University
Oklahoma City, Oklahoma, 71304
Woodlands Medical Specialists
Pensacola, Florida, 32503
Virginia Cancer Institute
Richmond, Virginia, 23230
Florida Cancer Specialists
St. Petersburg, Florida, 33705
Space Coast Cancer Center
Titusville, Florida, 32796
About this study
Official title: A Phase II Study of 5-Fluorouracil (5-FU), Aflibercept, and Radiation for the Preoperative and Adjuvant Treatment of Patients With Stage II/III Rectal Cancer
The purpose of this Phase II study will be to investigate the antiangiogenic agent, aflibercept, in combination with chemoradiation as preoperative treatment for patients with stage II/III rectal cancer, followed by 4 months of FOLFOX6 plus aflibercept adjuvantly.
- Conditions
- Rectal Cancer
- Being tested
- Radiation, Aflibercept, Surgery, FOLFOX6
- Keywords
- Rectal Cancer, Chemoradiation, Aflibercept, Surgery
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiationRadiation
AfliberceptDrug
Also called Eylea, Zaltrap
SurgeryProcedure or surgery
Abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines
FOLFOX6Drug
Also called Leucovorin (Folinic Acid), 5-Fluorouracil (5-FU; Efudex), Oxaliplatin (Eloxatin)
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX6/Aflibercept/Radiation/Surgery | Experimental | Preoperative Chemoradiation: (6 weeks)
* 5-FU: 225 mg/m2 per day by intravenous continuous infusion (IVCI), Days 1 thru 42;
* Radiation: 50.4 Gy (1.8 Gy/day or 28 fractions) Mon thru Fri, Weeks 1 thru 6;
* Aflibercept: 4 mg/ kg, via IV infusion, Days 1 and 15.
Surgery at least 6 weeks after last day of aflibercept: Patients will undergo abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines.
Postoperative Chemotherapy and Aflibercept Treatments (four 28-day cycles):
* Aflibercept (administered first): 4 mg/kg IV for approximately 1 hour (no more than 2 hours) on Days 1 and 15 of each cycle.
* Modified FOLFOX6:
* Leucovorin: 400 mg/m2 as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle.
* Oxaliplatin: 85 mg/m2 IV as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle.
* 5-FU: 400-mg/m2 bolus for 2 to 4 minutes followed by 2400 mg/m2 for 46 hours on Days 1 and 15 of each cycle. Receives: Radiation: Radiation; Drug: Aflibercept; Procedure: Surgery; Drug: FOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response Rate
The Pathologic Complete Response (pCR) Rate is defined as the number of pathologic complete responders among all patients evaluable for response, including evaluable patients who did not proceed to surgery. A pCR is defined as the absence of any residual abnormality detected in a pathological specimen.
Measured: Between days 57 and 98 after preoperative chemotherapy
Secondary outcomes (6)
Overall Survival
Measured from date of first protocol treatment until date of death.
Measured: Every 3 months (±1 month) following documented progression, up to 5 years or death, whichever comes first.
Overall Survival Probability at 6 and 12 Months
The probability of overall survival at 6 months and 12 months from date of first protocol treatment until date of death.
Measured: up to 1 year
Sphincter Preservation Rate
The percentage of patients who had Low Anterior Resection during surgery..
Measured: Between days 57 and 98 after preoperative chemotherapy.
Disease-Free Survival
Measured: Patients without evidence of progression will be followed every 3 months (±1 month) from date of last dose of study drug during Years 1-2, every 6 months during Years 3-4, and annually thereafter or until disease progression, estimated 5 years.
Disease Free Survival Probability at 6 and 12 Months
The probability of disease free survival at 6 and 12 months after initiating protocol treatment.
Measured: Up to 1 year
The Number of Participants Who Experienced Serious or Non-Serious Adverse Events as a Measure of Safety.
Adverse events and serious adverse events (AEs and SAEs) were graded according to National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0. Specific AE and SAE terms are provided in the Adverse Event module.
Measured: weekly for 6 weeks pre-op then every 2 weeks post-op, approximately 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2012 (estimated)
- Study startJan 2013
- Primary completionSep 2015
- Study completionSep 2015
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.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Johanna C Bendell, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01749956
- Sponsor's protocol ID
- SCRI GI 168
- Status last verified
- Dec 2016
- First submitted
- 12 Dec 2012
- Last updated
- 7 Feb 2017
- 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 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of 5-Fluorouracil (5-FU), Aflibercept, and Radiation for the Preoperative and Adjuvant Treatment of Patients With Stage II/III Rectal Cancer
- ClinicalTrials.gov ID
- NCT01749956
- Acronym / sponsor ID
- SCRI GI 168
- Conditions
- Rectal Cancer
- Keywords
- Rectal Cancer, Chemoradiation, Aflibercept, Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Jan 2013
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 17 Dec 2012 (estimated)
- Results
- Posted 7 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase II study will be to investigate the antiangiogenic agent, aflibercept, in combination with chemoradiation as preoperative treatment for patients with stage II/III rectal cancer, followed by 4 months of FOLFOX6 plus aflibercept adjuvantly.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FOLFOX6/Aflibercept/Radiation/Surgery | Experimental | Radiation: Radiation, Drug: Aflibercept, Procedure: Surgery, Drug: FOLFOX6Preoperative Chemoradiation: (6 weeks) * 5-FU: 225 mg/m2 per day by intravenous continuous infusion (IVCI), Days 1 thru 42; * Radiation: 50.4 Gy (1.8 Gy/day or 28 fractions) Mon thru Fri, Weeks 1 thru 6; * Aflibercept: 4 mg/ kg, via IV infusion, Days 1 and 15. Surgery at least 6 weeks after last day of aflibercept: Patients will undergo abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines. Postoperative Chemotherapy and Aflibercept Treatments (four 28-day cycles): * Aflibercept (administered first): 4 mg/kg IV for approximately 1 hour (no more than 2 hours) on Days 1 and 15 of each cycle. * Modified FOLFOX6: * Leucovorin: 400 mg/m2 as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle. * Oxaliplatin: 85 mg/m2 IV as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle. * 5-FU: 400-mg/m2 bolus for 2 to 4 minutes followed by 2400 mg/m2 for 46 hours 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 (10 listed)
- Patients with histologically confirmed stage II or III rectal cancer (adenocarcinoma)
- Patients must be candidates for preoperative chemoradiation
- Male or female patients ≥18 years-of-age
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
- Adequate hematologic, liver and renal function
Key exclusion criteria (21 listed)
- Treatment with prior chemotherapy or radiation for rectal cancer.
- Patients who have received any other investigational agents within the 28 days prior to Day 1 of the study.
- Known to be human immunodeficiency virus positive or hepatitis B or C positive
- Women who are pregnant or breastfeeding
- History of acute myocardial infarction within the previous 6 months, uncontrolled hypertension (blood pressure >150/100 mmHg and/or diastolic blood pressure >100 mmHg), unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication (excluding atrial fibrillation), or ≥ Grade 2 peripheral vascular disease.
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 |
|---|---|---|
| Radiation | Radiation | FOLFOX6/Aflibercept/Radiation/Surgery |
| AfliberceptAlso: Eylea, Zaltrap | Drug | FOLFOX6/Aflibercept/Radiation/Surgery |
| SurgeryAbdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines | Procedure or surgery | FOLFOX6/Aflibercept/Radiation/Surgery |
| FOLFOX6Also: Leucovorin (Folinic Acid), 5-Fluorouracil (5-FU; Efudex), Oxaliplatin (Eloxatin) | Drug | FOLFOX6/Aflibercept/Radiation/Surgery |
Primary outcome
Pathologic Complete Response Rate
Time frame: Between days 57 and 98 after preoperative chemotherapy
The Pathologic Complete Response (pCR) Rate is defined as the number of pathologic complete responders among all patients evaluable for response, including evaluable patients who did not proceed to surgery. A pCR is defined as the absence of any residual abnormality detected in a pathological specimen.
6 secondary outcomes
Overall Survival
Time frame: Every 3 months (±1 month) following documented progression, up to 5 years or death, whichever comes first.
Overall Survival Probability at 6 and 12 Months
Time frame: up to 1 year
Sphincter Preservation Rate
Time frame: Between days 57 and 98 after preoperative chemotherapy.
Disease-Free Survival
Time frame: Patients without evidence of progression will be followed every 3 months (±1 month) from date of last dose of study drug during Years 1-2, every 6 months during Years 3-4, and annually thereafter or until disease progression, estimated 5 years.
Disease Free Survival Probability at 6 and 12 Months
Time frame: Up to 1 year
The Number of Participants Who Experienced Serious or Non-Serious Adverse Events as a Measure of Safety.
Time frame: weekly for 6 weeks pre-op then every 2 weeks post-op, approximately 36 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Johanna C Bendell, M.D. study chair
SCRI Development Innovations, LLC
11 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 Radiation, Aflibercept and Surgery in people with Rectal Cancer, run by SCRI Development Innovations, LLC at 11 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 10 inclusion and 21 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 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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 7 Feb 2017). 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 Complete Response Rate (time frame: Between days 57 and 98 after preoperative chemotherapy). 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 Feb 2017.