5-FU, Aflibercept, and Radiation (RT) for Preoperative and Postoperative Patients With Stage II/III Rectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01749956
First received: December 12, 2012
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Rectal Cancer
Radiation: Radiation
Drug: Aflibercept
Procedure: Surgery
Drug: FOLFOX6
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Pathologic Complete Response Rate [ Time Frame: 15 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the toxicity of this regimen [ Time Frame: 15 months ] [ Designated as safety issue: Yes ]
  • Evaluate incidence of local and distant recurrence, overall survival (OS) and disease-free survival (DFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Evaluate the sphincter preservation rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: January 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFOX6/Aflibercept/Radiation/Surgery

Preoperative Chemoradiation:

  • 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: Patients will undergo abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines.

Postoperative Chemotherapy and Aflibercept Treatments:

  • 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
Drug: FOLFOX6
Other Names:
  • Leucovorin (Folinic Acid)
  • 5-Fluorouracil (5-FU; Efudex)
  • Oxaliplatin (Eloxatin)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01749956

Locations
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
Sanofi
Investigators
Study Chair: Johanna C Bendell, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01749956     History of Changes
Other Study ID Numbers: SCRI GI 168
Study First Received: December 12, 2012
Last Updated: October 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Rectal Cancer
Chemoradiation
Aflibercept
Surgery

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Fluorouracil
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014