Overview

Aflibercept and FOLFOX6 Treatment for Previously Untreated Stage IV Colorectal Cancer

Status:
Unknown status
Trial end date:
2019-12-31
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial studies how well giving aflibercept together with combination chemotherapy works in treating patients with previously untreated colon or rectal cancer that is metastatic or locally advanced and cannot be removed by surgery. Aflibercept may stop the growth of colon or rectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving aflibercept together with combination chemotherapy may kill more tumor cells
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
John Hays
Richard Goldberg
Collaborator:
Sanofi
Treatments:
Aflibercept
Endothelial Growth Factors
Fluorodeoxyglucose F18
Fluorouracil
Leucovorin
Oxaliplatin
Criteria
Inclusion Criteria:

- Histologically confirmed adenocarcinoma of colorectal origin that is metastatic or
locally advanced and unresectable

- Measurable disease, as defined by RECIST 1.1 criteria: one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
10 mm with spiral computed tomography (CT) scan (CT scan slice thickness no greater
than 5 mm) malignant lymph nodes will be considered measurable if they are >= 15 mm in
short axis

- Must not have received any prior systemic therapy for metastatic or locally advanced
CRC; prior VEGF inhibitors are not allowed

- Prior adjuvant therapy for CRC including fluoropyrimidines either alone or in
combination with oxaliplatin is allowed, provided that all therapy was completed >= 12
months from cancer recurrence, therapy duration was =< 6 months, and all prior
toxicities have completely resolved (residual grade 1 neuropathy is allowed)

- Life expectancy >= 12 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Hemoglobin >= 9 g/dL (blood transfusion permitted to attain this value)

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 2 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (may be =< 5x ULN if increase is due to metastatic disease)

- Creatinine =< 1.5 x institutional ULN or creatinine clearance >= 60 mL/min/1.73 m2 for
patients with creatinine levels above institutional U

- Urine protein:creatinine ratio (UPCR) < 1 or < 500 mg protein/24 hr

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- May not be receiving any other investigational agents

- Patients who have received any prior locoregional therapy for metastatic disease (e.g.
radiofrequency/microwave ablation, Yttrium-90 radioembolization, transarterial
chemoembolization, or surgical resection) are excluded

- Patients with known or suspected brain metastases, carcinomatous meningitis,
uncontrolled seizure disorder, active intracranial bleeding or active neurologic
disorder are excluded

- Patients with an active second primary malignancy or history of malignancy within the
5 years of enrollment are excluded, with the exception of non-melanoma skin cancers
and cervical cancer which has been treated with curative therapy

- Grade >= 2 sensory neuropathy at the time of enrollment

- Major surgery within 4 weeks of study start date; the surgical incision should be
fully healed prior to initiation of aflibercept

- Female or male patients of reproductive capacity unwilling to use methods appropriate
to prevent pregnancy are excluded; effective contraception is required for at least 3
months following the last administration of aflibercept

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, uncontrolled hypertension (blood pressure [BP] must be well controlled <
160/90), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements, or any condition that
the principal investigator (PI) feels would make the patient ineligible

- Positive pregnancy screening test with a minimum sensitivity of 25 IU/L of human
chorionic gonadotropin (hCG) within 72 hours of registration; breastfeeding women are
also excluded

- History of pulmonary embolus within 3 months or deep venous thrombosis (DVT) within 4
weeks of enrollment; patients on anticoagulation must be on a stable dose of warfarin
with a therapeutic-range international normalized ratio (INR) or on a stable dose of
low molecular weight heparin

- Active congestive heart failure (New York Heart Association [NYHA] class II-IV)

- History of an arterial thrombotic vascular event including cerebrovascular accident
(CVA), myocardial infarction (MI), unstable angina, coronary or peripheral arterial
bypass graft, or transient ischemic attack (TIA) within 6 months

- Serious or non-healing wound, ulcer or bone fracture at the time of medication
administration

- History of treatment-resistant peptic ulcer disease, erosive esophagitis, gastritis,
or diverticulitis within 3 months

- History of gastrointestinal (GI) perforation within 5 years; current or prior
intestinal fistulas are also excluded

- Known chronic infectious disease including human immunodeficiency virus (HIV)/acquired
immune deficiency syndrome (AIDS)

- History of major hemorrhage including gastrointestinal bleeding (grade 2-4), pulmonary
hemorrhage, or clinically significant hemoptysis (> 1 tsp in 24 hours) within the last
5 years; patients with underling conditions that predispose to bleeding, such as
bleeding diathesis, known esophageal varices, or tumor involving major vessels, are
also excluded

- Inability to understand or comply with study protocol

- Known hypersensitivity to Chinese hamster ovary cell products or to recombinant human
or murine antibodies, or any of the treatments in this protocol