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

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01749956
• Other study ID #: SCRI GI 168
• Status: Completed
• Phase: Phase 2
• First received: December 12, 2012
• Last updated: April 1, 2016
• Start date: January 2013
• Est. completion date: September 2015

Study information

• Verified date: April 2016
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Radiation:
• Radiation

Drug:
• Aflibercept

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

Drug:
• FOLFOX6

Locations

Country	Name	City	State
United States	Tennessee Oncology - Chattanooga	Chattanooga	Tennessee
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Baptist Hospital East	Louisville	Kentucky
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Oklahoma University	Oklahoma City	Oklahoma
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Florida Cancer Specialists	St. Petersburg	Florida
United States	Space Coast Cancer Center	Titusville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response Rate	Pathological specimen with no residual abnormality detected. Defined as the percentage of pathologic complete responders.	15 months	No
Secondary	Frequency of adverse events and serious adverse events as a measure of safety.	Worst toxicity grades per patient will be tabulated using National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0.	weekly for 6 weeks pre-op then every 2 weeks post-op, projected 6 months	Yes
Secondary	Overall Survival	Measured from date of first protocol treatment until date of death.	Every 3 months (±1 month) following documented progression, up to 5 years or death, whichever comes first.	No
Secondary	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.	No