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5-FU, Aflibercept, and Radiation (RT) for Preoperative and Postoperative Patients With Stage II/III 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: NCT01749956
Recruitment Status : Completed
First Posted : December 17, 2012
Results First Posted : February 7, 2017
Last Update Posted : February 7, 2017
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Rectal Cancer Radiation: Radiation Drug: Aflibercept Procedure: Surgery Drug: FOLFOX6 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2013
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: FOLFOX6/Aflibercept/Radiation/Surgery

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.
Radiation: Radiation
Drug: Aflibercept
Other Names:
  • Eylea
  • Zaltrap

Procedure: Surgery
Abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines

Other Names:
  • Leucovorin (Folinic Acid)
  • 5-Fluorouracil (5-FU; Efudex)
  • Oxaliplatin (Eloxatin)

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Every 3 months (±1 month) following documented progression, up to 5 years or death, whichever comes first. ]
    Measured from date of first protocol treatment until date of death.

  2. Overall Survival Probability at 6 and 12 Months [ Time Frame: up to 1 year ]
    The probability of overall survival at 6 months and 12 months from date of first protocol treatment until date of death.

  3. Sphincter Preservation Rate [ Time Frame: Between days 57 and 98 after preoperative chemotherapy. ]
    The percentage of patients who had Low Anterior Resection during surgery..

  4. 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. ]
  5. Disease Free Survival Probability at 6 and 12 Months [ Time Frame: Up to 1 year ]
    The probability of disease free survival at 6 and 12 months after initiating protocol treatment.

  6. 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 ]
    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.

Information from the National Library of Medicine

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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. Patients with histologically confirmed stage II or III rectal cancer (adenocarcinoma)
  2. Patients must be candidates for preoperative chemoradiation
  3. Male or female patients ≥18 years-of-age
  4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
  5. Adequate hematologic, liver and renal function
  6. Male patients willing to use adequate contraceptive measures
  7. 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
  8. Life expectancy ≥12 weeks
  9. Willingness and ability to comply with the trial and follow-up procedures
  10. Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

  1. Treatment with prior chemotherapy or radiation for rectal cancer.
  2. Patients who have received any other investigational agents within the 28 days prior to Day 1 of the study.
  3. Known to be human immunodeficiency virus positive or hepatitis B or C positive
  4. Women who are pregnant or breastfeeding
  5. 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.
  6. History of hypertensive crisis or hypertensive encephalopathy.
  7. History of stroke or transient ischemic attack within the past 6 months.
  8. Significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of therapy.
  9. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
  10. Patients with symptomatic sensory or peripheral neuropathy (Grade 2 or above).
  11. Patients may not have received other agents, either investigational or marketed, that act by primary anti-angiogenic mechanisms.
  12. 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.
  13. Patients with active concurrent infections or patients with serious underlying medical conditions.
  14. 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.
  15. 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.
  16. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of therapy.
  17. 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.
  18. Any non-healing wound, ulcer, or bone fracture.
  19. Any clinical evidence or history of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  20. History of hemoptysis (≥½ teaspoon of bright red blood per episode) within 1 month prior to initiation of therapy.
  21. 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

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): NCT01749956

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United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33916
Woodlands Medical Specialists
Pensacola, Florida, United States, 32503
Florida Cancer Specialists
St. Petersburg, Florida, United States, 33705
Space Coast Cancer Center
Titusville, Florida, United States, 32796
United States, Kentucky
Baptist Hospital East
Louisville, Kentucky, United States, 40207
United States, Ohio
Oncology Hematology Care, Inc.
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
Oklahoma University
Oklahoma City, Oklahoma, United States, 71304
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Tennessee
Tennessee Oncology - Chattanooga
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23230
Sponsors and Collaborators
SCRI Development Innovations, LLC
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Study Chair: Johanna C Bendell, M.D. SCRI Development Innovations, LLC

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Responsible Party: SCRI Development Innovations, LLC Identifier: NCT01749956    
Other Study ID Numbers: SCRI GI 168
First Posted: December 17, 2012    Key Record Dates
Results First Posted: February 7, 2017
Last Update Posted: February 7, 2017
Last Verified: December 2016
Keywords provided by SCRI Development Innovations, LLC:
Rectal Cancer
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs