Short-Infusion Ziv-aflibercept in Treating Patients With Metastatic Colorectal Cancer Receiving Combination Chemotherapy

PRIMARY OBJECTIVES:

I. To determine the feasibility of a shorter infusion of 30 minutes and 15 minutes of
standard dose ziv-aflibercept when combined with FOLFIRI (folinic acid [leucovorin calcium],
fluorouracil, and irinotecan [irinotecan hydrochloride]) in patients with metastatic
colorectal cancer.

SECONDARY OBJECTIVES:

I. Describe the institutional safety experience with this combination using Common
Terminology Criteria for Adverse Events (CTCAE) version 4 for toxicity grading.

OUTLINE:

Patients receive ziv-aflibercept intravenously (IV) over 15-30 minutes followed by FOLFIFRI
chemotherapy comprising leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over
90 minutes, and fluorouracil IV over 46 hours on day 1. Courses repeat every 2 weeks in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Patients with metastatic colorectal cancer are eligible for this study; colorectal
cancer should have been previously confirmed by pathology or cytology; to be eligible
for this protocol, patients should be receiving ziv-aflibercept plus FOLFIRI as a
standard treatment prior to enrolling on this trial; the number and type of therapy
administered prior to enrollment will not affect the ability to enroll on this study

- Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0, 1, or 2

- Patients should have an expected life expectancy of 12 weeks or longer

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control or abstinence) prior to study entry and
for six months following duration of study participation; should a woman become
pregnant or suspect that she is pregnant while participating on the trial, she should
inform her treating physician immediately

- To be eligible for this study, patients should already be receiving a standard dose
of ziv-aflibercept intravenously over 60 minutes in combination with FOLFIRI
chemotherapy every 2 weeks without evidence of progressive disease; treatment on this
study can start as early as two weeks from last "off protocol" ziv-aflibercept plus
FOLFIRI cycle, granted treatment parameters have been met

- Total bilirubin < 1.5 upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 ULN unless
patient has metastatic disease to the liver in which case < 5 ULN will be allowed

- Serum creatinine < 1.5 ULN

- Urine protein/creatinine ration (UPCR) =< 1 or total urinary protein of < 1 gm/24
hours in the event the UPCR > 1

- Systolic blood pressure < 155 mm mercury and diastolic blood pressure < 100 mm
mercury documented on two separate occasions at least 24 hours apart

- Platelet counts >= 75,000/mm^3

- Neutrophil count >= 1500/mm^3

- Hemoglobin >= 9 gm/dl; anemia can be corrected with transfusion to allow eligibility
prior to enrollment

- Hematological tests can be repeated to assess eligibility

- No unresolved grade 2 or above non-hematological toxicities, with the exception of
alopecia or neuropathy

- All subjects must have the ability to understand and the willingness to sign a
written consent

Exclusion Criteria:

- Patients should not have any uncontrolled illness such as congestive heart failure,
respiratory distress, and including ongoing or active infection

- Patients may not be receiving any other investigational agents, or concurrent
biological, chemotherapy, or radiation therapy with the exception of study drugs

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ziv-aflibercept

- Patients should be at least 2 weeks from their last dose of ziv-aflibercept when they
receive their first dose of study treatment

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated on this study

- Patients with other active malignancies are ineligible for this study with the
exception of non-melanoma skin cancer that is amenable to excision, cervical
carcinoma in situ, hormone sensitive prostate cancer, or prostate cancer with no
measurable disease (watchful waiting)

- History of arterial thrombotic events within 1 year prior to enrollment on study

- Surgical intervention within 4 weeks prior to study initiation and no open wounds

- Clinically significant bleeding; clinically significant bleeding is defined as
gastrointestinal bleeding requiring a blood transfusion, bleeding manifesting as
melena, or blood per rectum estimated to exceed 2 tablespoons within 4 weeks prior to
enrollment; hemoptysis associated with blood loss of more than 1/2 tablespoon per day
is also considered significant; physician judgment will be used to estimate presence
or lack of significant clinical bleeding

- History of bowel perforation

- History of intracranial bleeding

- History of reversible posterior leukoencephalopathy syndrome (RPLS)

- History of active fistula

- Subjects, who in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study will be excluded