Cetuximab and/or Dasatinib in Patients With Colorectal Cancer and Liver Metastases That Can Be Removed by Surgery

NCT00835679 | Terminated Early Phase 1 Results

• 6 other identifiers: NCI-2013-00014VU-VICC-GI-08388069P30CA068485081338VICC GI 0838
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This phase 0 trial is studying whether 2 weeks of cetuximab and dasatinib will change tumor cells in patients with colorectal cancer and liver metastases that can be removed by surgery. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Patients With a Biologic Response

  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%).

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

Secondary Outcomes (3)

• Patients With Reduction of Biomarkers in Tumor Tissue

  study entry to day 15

• Number of Patients With the Given Severity of Adverse Event Within a Specified Duration

  weekly to day 15, and at followup on day 30

• Number of Patients With the Given Severity of Post-operative Complications Within the Specified Duration

  From day 15 (day of surgery) to 30 days after surgery

Study Arms (4)

Cohort A (no systemic neoadjuvant therapy)

EXPERIMENTAL

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.

Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

Cohort B (cetuximab)

EXPERIMENTAL

Patients receive 400 mg/m\^2 cetuximab IV over 120 minutes on day 1 and 250 mg/m\^2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15.

Biological: cetuximab; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

Cohort C (dasatinib)

EXPERIMENTAL

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

Drug: dasatinib; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

Cohort D (cetuximab, dasatinib)

EXPERIMENTAL

Patients receive 400 mg/m\^2 cetuximab IV over 120 minutes on day 1 and 250 mg/m\^2 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.

Biological: cetuximab; Drug: dasatinib; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

Interventions

cetuximab BIOLOGICAL

Given IV

Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

Cohort B (cetuximab); Cohort D (cetuximab, dasatinib)

dasatinib DRUG

Given orally

Also known as: BMS-354825, Sprycel

Cohort C (dasatinib); Cohort D (cetuximab, dasatinib)

therapeutic conventional surgery PROCEDURE

Undergo surgery

Cohort A (no systemic neoadjuvant therapy); Cohort B (cetuximab); Cohort C (dasatinib); Cohort D (cetuximab, dasatinib)

laboratory biomarker analysis OTHER

Correlative studies

Cohort A (no systemic neoadjuvant therapy); Cohort B (cetuximab); Cohort C (dasatinib); Cohort D (cetuximab, dasatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Absolute neutrophil count \>= 1.5 x 10\^9/L
• Hemoglobin ≥ 9.0 Gm/dL
• Platelets \>= 100 x 10\^9/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine transaminase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal
• Creatinine =\< 1.5 institutional ULN
• 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 KRAS status will be evaluated in the tumor, wild type KRAS status is not an eligibility criterion

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Cetuximab; Dasatinib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Due to study design and slow accrual, no drug was received, no biomarkers were determined and no data obtained. "0" data is entered in the outcomes measures database as suggested by CT.gov previously. Detailed explanations are given.

Results Point of Contact

• Title: Emily Chan, MD
• Organization: Vanderbilt-Ingram Cancer Center

emily.chan@vanderbilt.edu

615-343-4677

Study Officials

• Emily Chan

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2009
• First Posted: February 4, 2009
• Study Start: December 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: August 1, 2011
• Last Updated: May 23, 2014
• Results First Posted: September 7, 2012

Record last verified: 2013-01

Locations

US (2)