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A Preoperative Biological Trial of Cetuximab, Dasatinib or the Combination in Colorectal Cancer Patients With Resectable Liver Metastases


N/A
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer, Metastatic Cancer

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Trial Information

A Preoperative Biological Trial of Cetuximab, Dasatinib or the Combination in Colorectal Cancer Patients With Resectable Liver Metastases


OBJECTIVES:

- To evaluate the biological effects of cetuximab and/or dasatinib on epidermal growth
factor receptor (EGFR)and Src-signaling pathways in patients with colorectal cancer and
resectable liver metastases.

OUTLINE: This is a multicenter study. Patients are initially enrolled in cohort A. Once
cohort A is completed, additional patients are enrolled and randomized to treatment in
either cohorts B or C. If a significant biological effect is seen in cohorts B or C,
additional patients are enrolled in cohort D.

- Cohort A: Patients receive no systemic neoadjuvant therapy between enrollment and the
time of definitive surgical resection of liver metastases. Liver biopsies were
performed at surgery since this cohort received no systemic therapy.

- Cohort B: Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on
day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical
resection of liver metastases will take place on day 15

- Cohort C: Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive
surgical resection of liver metastases will take place on day 15

- Cohort D: Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on
day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg
orally once daily on days 1-14. Definitive surgical resection of liver metastases will
take place on day 15

Patients undergo tumor tissue (from initial liver tumor biopsies and liver resection
samples), serum, and peripheral blood mononuclear cell sample collection periodically for
biomarker analysis via immunohistochemistry (IHC).

Inclusion Criteria


Inclusion criteria

- Patients must have histologically confirmed adenocarcinoma arising from the large
intestine that has metastasized to the liver. Liver metastases may be synchronous or
metachronous.

- The liver metastases must be considered surgically resectable prior to the initiation
of study drugs.

- Prior chemotherapy or chemoradiotherapy for colorectal cancer is allowed provided
that toxicities from prior therapy have resolved to Grade 1 or less. No prior
anti-EGFR or anti-Src therapy is allowed.

- Age >18 years.

- Eastern Cooperative Oncology Group (ECOG) performance status < 1 (Karnofsky >60%)

- Patients must have organ and marrow function within the parameter defined below:

- absolute neutrophil count > 1.5 x 109/L

- hemoglobin ≥ 9.0 Gm/dL

- platelets > 100 x 109/L

- total bilirubin ≤ 1.5 x Institutional Upper Limits of Normal (IULN)

- aspartate aminotransferase(serum glutamic oxaloacetic transaminase)/alanine
transaminase(serum glutamic pyruvic transaminase) (AST, SGPT/ALT, SGPT) < 5 x
IULN

- creatinine < 1.5 IULN

- Women must have a negative pregnancy test. 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. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

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

- Although K-Ras status will be evaluated in the tumor, wild type K-Ras status is not
an eligibility criterion.

Exclusion Criteria

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cetuximab or dasatinib.

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with cetuximab or
dasatinib, breastfeeding should be discontinued if the mother is treated with
cetuximab or dasatinib.

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with cetuximab or dasatinib. Appropriate studies will
be undertaken in patients receiving combination anti-retroviral therapy when
indicated.

- Patients on potent CYP3A4 inducers and inhibitors.

Inclusion of Women and Minorities Both men and women and members of all races and ethnic
groups are eligible for this trial.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Patients With a Biologic Response

Outcome Description:

Patients who experienced a pre-to-post treatment reduction of at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker of the pathway being inhibited: epidermal growth factor (EGFR) for Cohort B, sarcoma (Src) for Cohort C, and both EGFR and Src for Cohort D. Blood for these biomarkers will be taken on day of baseline and pre-operatively on day 15. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for pathway in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%).

Outcome Time Frame:

on baseline and preoperatively on day of surgery (day 15)

Safety Issue:

No

Principal Investigator

Emily Chan, MD, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00014

NCT ID:

NCT00835679

Start Date:

December 2009

Completion Date:

August 2011

Related Keywords:

  • Colorectal Cancer
  • Metastatic Cancer
  • adenocarcinoma of the colon
  • recurrent colon cancer
  • stage IV colon cancer
  • adenocarcinoma of the rectum
  • recurrent rectal cancer
  • stage IV rectal cancer
  • liver metastases
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Liver Neoplasms

Name

Location

Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Moffitt Cancer CenterTampa, Florida  33612
Vanderbilt-Ingram Cancer Center - Cool SpringsNashville, Tennessee  37064