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

This study is currently recruiting participants.
Verified April 2014 by SCRI Development Innovations, LLC
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01749956
First received: December 12, 2012
Last updated: April 11, 2014
Last verified: April 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 Therapy
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 ]
  • Examine the levels of vascular endothelial growth factor A (VEGF-A) and placental growth factor (PLGF) and correlate with response [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 39
Study Start Date: January 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFOX6/Aflibercept/Radiation Therapy

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 Therapy 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 (see Appendix A)
  5. Adequate hematologic function (within 7 days prior to initial treatment) defined as:

    Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100,000/uL Hemoglobin ≥9 g/dL

  6. Adequate liver function defined as:

    Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) ≤3 x the upper limit of normal (UNL) Total bilirubin ≤3.0 mg/dL

  7. Adequate renal function defined as serum creatinine ≤1.6 mg/dL
  8. Male patients willing to use adequate contraceptive measures (see Appendix B)
  9. Female patients who are not of child-bearing potential (see Appendix B), and female patients of child-bearing potential who agree to use adequate contraceptive measures (see Appendix B), who are not breastfeeding, and who have a negative serum or urine pregnancy test <7 days prior
  10. Life expectancy ≥12 weeks
  11. Willingness and ability to comply with the trial and follow-up procedures
  12. 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 (see Appendix C), 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 external biliary stents.
  18. 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.
  19. Any non-healing wound, ulcer, or bone fracture.
  20. Any clinical evidence or history of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  21. History of hemoptysis (≥½ teaspoon of bright red blood per episode) within 1 month prior to initiation of therapy.
  22. 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749956

Contacts
Contact: Johanna C Bendell, M.D. asksarah@scresearch.net

Locations
United States, Florida
Florida Cancer Specialists Recruiting
Fort Myers, Florida, United States, 33916
Contact       asksarah@scresearch.net   
Woodlands Medical Specialists Recruiting
Pensacola, Florida, United States, 32503
Contact: AskSARAH       AskSARAH@scresearch.net   
Florida Cancer Specialists Recruiting
St. Petersburg, Florida, United States, 33705
Contact: AskSARAH       AskSARAH@scresearch.net   
Space Coast Cancer Center Recruiting
Titusville, Florida, United States, 32796
Contact       lindap@spacecoastcancer.com   
United States, Kentucky
Baptist Hospital East Recruiting
Louisville, Kentucky, United States, 40207
Contact: AskSARAH       AskSARAH@scresearch.net   
United States, Ohio
Oncology Hematology Care, Inc. Recruiting
Cincinnati, Ohio, United States, 45242
Contact: AskSARAH       AskSARAH@scresearch.net   
United States, Oklahoma
Oklahoma University Recruiting
Oklahoma City, Oklahoma, United States, 71304
United States, South Carolina
South Carolina Oncology Associates Recruiting
Columbia, South Carolina, United States, 29210
Contact: AskSARAH       AskSARAH@scresearch.net   
United States, Tennessee
Tennessee Oncology - Chattanooga Recruiting
Chattanooga, Tennessee, United States, 37404
Contact: AskSARAH       AskSARAH@scresearch.net   
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: AskSARAH       AskSARAH@scresearch.net   
United States, Virginia
Virginia Cancer Institute Recruiting
Richmond, Virginia, United States, 23230
Contact: AskSARAH       AskSARAH@scresearch.net   
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: April 11, 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
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 17, 2014