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BrUOG C261:Single Agent Adjuvant Aflibercept for Patients With Resected or Ablated Metastatic Colorectal Cancer: A Randomized Phase II Study

Phase 2
18 Years
Open (Enrolling)
Metastatic Colorectal Cancer

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Trial Information

BrUOG C261:Single Agent Adjuvant Aflibercept for Patients With Resected or Ablated Metastatic Colorectal Cancer: A Randomized Phase II Study

There are over 1.2 million new cases of colorectal cancer and 600,000 deaths worldwide. The
liver is the dominant site of metastases. Approximately 20-25% of patients with advanced
colorectal cancer will be candidates for resection/ablation of all sites of metastatic
disease.1 Unfortunately, despite resection/ablation of all metastatic sites only about 20%
of these patients are ultimately cured.1 An effective adjuvant agent would prevent tumor

Aflibercept and bevacizumab are effective when combined with FOLFIRI for metastatic colon
cancer. Neither has been tested in a randomized study in the adjuvant setting for patients
with resected metastatic disease. Since aflibercept more effectively inhibits all forms of
VEGF including VEGF-A, VEGF-B and PIGF, in striking contrast to bevacizumab which inhibits
only VEGF-A, aflibercept likely will be more effective than bevacizumab as a single agent in
the adjuvant metastatic setting. Therefore, we propose a randomized study of adjuvant
aflibercept for patients metastatic colorectal cancer who have received 10-12 cycles of
perioperative FOLFOX and have had had a complete response to all sites of metastases after
chemotherapy and local modalities such as surgical resection or ablation. SBRT may also be
used to produce a complete response in a metastatic site not easily amenable to surgery or
ablation. Only patients with very high risk of recurrence, defined as 3 or more metastatic
sites, will be included in this study.

Inclusion Criteria:

- First-line treatment of metastatic colorectal cancer with 3 or more metastases

- At least 10 cycles of FOLFOX. (Patients unable to complete 10 cycles of oxaliplatin,
such as due to neuropathy or hypersensitivity reaction, may complete 10 cycles of
treatment with 5-FU/leucovorin or FOLFIRI)

- No prior bevacizumab.

- Resection or ablation of all metastatic sites that have not achieved complete
response with chemotherapy. The sequence of surgery, ablation and chemotherapy may be
according to standard institutional procedure.

- Patients achieving a complete response in a metastatic site by stereotactic body
radiation are eligible if the site was not easily accessible by surgery or ablation
and a complete response was achieved.

- No severe, uncontrolled concurrent illness that would interfere with protocol

- No CNS disease

- ECOG Performance Status 0-2

- No chemotherapy or radiation therapy within last 3 weeks

- For patients who had 3 months of chemo, then surgery, then 3 months of chemo,
patients must be off chemotherapy for no more than 8 weeks prior to randomization.
For patients who had all their chemo and then surgery, they must be no more than 8
weeks from surgery prior to randomization.

- No concurrent anticancer therapy.

- Absolute neutrophil count ≥ 1,500/uL, Hgb > 9.0 g/dl, platelet ≥ 100,000/uL.

- Total bilirubin ≤ 1.5x upper limit of normal (ULN), AST or ALT ≤ 5x ULN;

- Creatinine < 1.5 x ULN

- Life expectancy of at least 12 weeks.

- Age ≥ 18 years

- Women of childbearing potential must have a negative pregnancy test.

- Men and women of childbearing potential must be willing to consent to using effective
contraception while on treatment and for at least 3 months thereafter.

- Voluntary written informed consent.

Exclusion Criteria:

- Residual metastatic disease after resection, ablation and chemotherapy

- Clinically significant cardiac disease (e.g., uncontrolled hypertension [blood
pressure of >160/90 mmHg on medication], history of myocardial infarction within 6
months,), New York Heart Association (NYHA) Class II or greater congestive heart
failure within 6 months, unstable arrhythmia. Patients with an atrial arrhythmia must
have this condition well controlled on stable medication. Patients with current or
recent (within 6 months) unstable angina are also not eligible.

- Significant bleeding diathesis or coagulopathy

- History of cerebral aneurysms or cerebral arteriovenous malformations.

- Patients with recent (within 12 months) arterial thromboembolic events, including
transient ischemic attack (TIA), cerebrovascular accident (CVA), or clinically
significant peripheral artery disease should also be excluded.

- Patients with a history of a gastrointestinal fistula or perforation.

- Women who are breast-feeding.

- Patients who have undergone major surgery, chemotherapy, or radiotherapy within the
last 3 weeks.

- Patients on concurrent anticancer therapy.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease free survival in patients with advanced colorectal cancer who have undergone resection/ablation of all metastatic sites.

Outcome Time Frame:

Every 3 months until disease progression with no estimated time period

Safety Issue:


Principal Investigator

Howard Safran, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Brown University Oncology Research Group


United States: Food and Drug Administration

Study ID:

BrUOG C261



Start Date:

December 2012

Completion Date:

January 2016

Related Keywords:

  • Metastatic Colorectal Cancer
  • Metastatic
  • Colorectal
  • Colorectal Cancer
  • Resected or Ablated Metastatic Colorectal Cancer
  • Colorectal Neoplasms



Rhode Island Hospital Providence, Rhode Island  02903
Virginia Mason Medical Center Seattle, Washington  98111
Thomas Jefferson University Hospital Philadelphia, Pennsylvania  19131
The Miriam Hospital Providence, Rhode Island  02903
Wake Forest Medical Center Winston-Salem, North Carolina  27157
Stanford Hospital and Clinic Palo Alto, California  94305
University of Vermont Medical Center Burlington, Vermont  05401