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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



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