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

NCT01749956 | Completed Phase 2 Results

• 1 other identifier: SCRI GI 168
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 11

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.

Conditions

Rectal Cancer

Keywords

Rectal Cancer; Chemoradiation; Aflibercept; Surgery

Outcome Measures

Primary Outcomes (1)

• 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.

  Between days 57 and 98 after preoperative chemotherapy

Secondary Outcomes (6)

• Overall Survival

  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

  up to 1 year

• Sphincter Preservation Rate

  Between days 57 and 98 after preoperative chemotherapy.

• Disease-Free Survival

  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

  Up to 1 year

Study Arms (1)

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.

Radiation: Radiation; Drug: Aflibercept; Procedure: Surgery; Drug: FOLFOX6

Interventions

Radiation RADIATION

FOLFOX6/Aflibercept/Radiation/Surgery

Aflibercept DRUG

Also known as: Eylea, Zaltrap

FOLFOX6/Aflibercept/Radiation/Surgery

Surgery PROCEDURE

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

FOLFOX6/Aflibercept/Radiation/Surgery

FOLFOX6 DRUG

Also known as: Leucovorin (Folinic Acid), 5-Fluorouracil (5-FU; Efudex), Oxaliplatin (Eloxatin)

FOLFOX6/Aflibercept/Radiation/Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Sanofi: collaborator

Study Sites (11)

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Woodlands Medical Specialists

Pensacola, Florida, 32503, United States

Location

Florida Cancer Specialists

St. Petersburg, Florida, 33705, United States

Location

Space Coast Cancer Center

Titusville, Florida, 32796, United States

Location

Baptist Hospital East

Louisville, Kentucky, 40207, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Oklahoma University

Oklahoma City, Oklahoma, 71304, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiation; aflibercept; Surgical Procedures, Operative; Folfox protocol; Leucovorin; Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Charles Davis, RAC
• Organization: SCRI Development Innovations

charles.davis2@scri-innovations.com

615-524-4341

Study Officials

• Johanna C Bendell, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2012
• First Posted: December 17, 2012
• Study Start: January 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: February 7, 2017
• Results First Posted: February 7, 2017

Record last verified: 2016-12

Locations

US (11)