Phase II Study of Zaltrap and Chemotherapy for Advanced Resectable Colorectal Cancer

Status:Not yet recruiting
Conditions:Colorectal Cancer, Colorectal Cancer, Colorectal Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:February 2014
End Date:February 2018
Contact:Alice Mercado, RN

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Phase II Study of Preoperative Chemotherapy With Ziv-aflibercept (Zaltrap) Followed by Postoperative Chemotherapy With or Without Ziv-aflibercept (Zaltrap) in Patients With Advanced Resectable Colorectal Cancer

The purpose of this study is to establish the safety of Zaltrap in patients who undergo
pre-operative chemotherapy with Zaltrap. The investigators hypothesize that Zaltrap my
impact colorectal cancer growth and metastasis.

Eligible patients will receive 3 months of chemotherapy consisting of either FOLFOX or
FOLFIRI (in the case of liver limited CRC) or FOLFOX (in the case of rectal cancer). The
FOLFOX regimen consists of Oxaliplatin, Leucovorin, and 5-FU. The FOLFIRI regimen consists
of Irinotecan, Leucovorin, and 5-FU. Zaltrap will be administered with chemotherapy every 2
weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery
period (i.e. 5-6 week's from the last Zaltrap dose), patients will undergo standard
resection. At the time of resection, the tumor will be collected for biomarker discovery.

Following resection, patients will be randomly assigned (1:1) to receive chemotherapy with
or without zaltrap for 3 additional months. Patients assigned to Zaltrap may continue
zaltrap (without chemotherapy) until disease recurrence or up to an additional 15 months.
Patients will have research blood draws periodically both in the preoperative and
postoperative period.

The investigators plan to demonstrate that pre-operative chemotherapy with Zaltrap is not
associated with any safety signals that would preclude further drug development in this
patient population. The investigators also plan to perform correlative studies to identify
potential biomarkers for Zaltrap activity.

The investigators hypothesize that antiangiogenic therapy may specifically target the
micrometastatis niche of patients with liver limited metastatic colorectal cancer to
significantly increase the chance of cure for these patients.

Inclusion Criteria:

- Patients must have pathologically confirmed adenocarcinoma of the colon or rectum.

- In patients with liver-limited metastatic colorectal cancer, a curative approach is
indicated following evaluation by hepatobiliary surgeon as part of multidisciplinary
management. Select patients requiring two stage procedure are also eligible following
evaluation by hepatobiliary surgeon as part of multidisciplinary management.

- In patients with rectal cancer, primary tumor that is clinically T3-4 or N +
(evaluation by colorectal surgery is required as part of multidisciplinary approach).

- No prior chemotherapy for metastatic disease is allowed for patients with CRC-liver
mets. (adjuvant FOLFOX is permitted)

- No prior chemotherapy for proximal rectal cancer is allowed

- ECOG Performance status ≤ 2.

- Age >18 years old.

- Patients must have adequate bone marrow, kidney, and liver function as assessed by
laboratory parameters.

1. WBC ≥ 3,000/uL

2. Total Bilirubin ≤ 1.5 x upper limits of normal

3. AST (SGOT) ≤ 3 x upper limits of normal

4. ALT (SGPT) ≤ 3 x upper limits of normal

5. Hemoglobin ≥ 9.0 g/dl (without transfusion within 7 d)

6. ANC ≥ 1500 /ml

7. Platelets ≥100 K/ml (without transfusion)

8. Calculated CrCL > 50 ml/min

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

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation.

Exclusion Criteria:

- Patients with untreated CNS metastases.

- Significant medical co-morbidity that would preclude safe administration of cytotoxic
therapy, including but not limited to:

1. Cardiovascular disease

1. Unstable angina

2. Myocardial infarction/ CABG < 3 months prior to study initiation

3. Untreated coronary artery disease

4. NYHA class III or IV heart failure

2. Ongoing serious infection

1. Bacteremia or sepsis requiring intravenous antibiotics

2. HIV with AIDS defining illness

3. Inadequate oral nutritional intake: Requirement for daily intravenous fluids or
total parenteral nutrition.

4. Neurological: Stroke ≤ 6 months

5. Psychiatric illness/social situations that would limit compliance with study

- Patients may not receive another investigational agent.

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

- Pregnant (positive pregnancy test) and lactating women are excluded from the study
because the risks to an unborn fetus or potential risks in nursing infants are

- Major surgical procedure ≤ 4 weeks from starting therapy.

- Grade 3-4 hemorrhage, erosive esophagitis or gastritis, infectious or inflammatory
bowel disease, or diverticulits ≤ 3 months from starting therapy.

- Patients with known DPD deficiency

- Patients with known Gilbert's syndrome

- Patients with ≥ 2g/24 hour urine protein. If urine protein on random UA is ≤ 300
mg/dl, a 24 hour urine protein is not required.

- Symptomatic peripheral sensory neuropathy grade ≥ 2.

- Other malignancy within the last 5 years from study entry, except for basal /squamous
cell skin cancer, in situ cervical cancer, or non-metastatic prostate cancer.
We found this trial at
New York City, New York 10065
New York City, NY
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