ZD6474, Cetuximab, and Irinotecan in Patients With Metastatic Colorectal Cancer

NCT00436072 | Completed Phase 1

• 1 other identifier: 06-177
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

This research study will test the safety of the investigational drug, ZD6474, in combination with 2 other drugs that are standard in the treatment of colon and rectal cancer (cetuximab and irinotecan). ZD6474 blocks the action of two substances in the body: vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR stimulates the formation of new blood vessels. When cancer cells produce VEGFR, new blood vessels are made that provide blood to the cancer cells. The blood carries nutrients and oxygen, allowing the cancer cells to live and grow. EGFR controls how quickly cells grow and multiply. Both of these substances are found on normal cells, but they are found in much higher levels on cancer cells.

Conditions

Colorectal Cancer

Keywords

ZD6474; cetuximab; irinotecan

Outcome Measures

Primary Outcomes (1)

• To determine the tolerability and maximum tolerated dose of combining ZD6474, cetuximab and irinotecan in patients with metastatic colorectal cancer refractory to prior cytotoxic chemotherapy.

  Years

Secondary Outcomes (1)

• Determine response rate, progression-free survival and overall survival of adding ZD6474 to cetuximab and irinotecan in this patient population.

  Years

Interventions

ZD6474 DRUG

Orally on a daily basis

Cetuximab DRUG

Infusion once weekly

Irinotecan DRUG

Infusion once the safe dose of ZD6474 and cetuximab is established

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented locally advanced or metastatic colorectal cancer
• prior therapies for metastatic colorectal cancer. Prior adjuvant therapy not included in the number of priors unless recurrence within 12 months of last dose of therapy and then the adjuvant therapy will be counted.
• Tumor is K-ras wildtype by method of choice at respective institution (testing codons 12 and 13)
• Measurable disease according to the RECIST criteria
• years of age or older
• ECOG Performance Status of 0-2
• Completed any major surgery 4 weeks from registration and any minor surgery 2 weeks from registration
• Adequate bone marrow function
• Adequate renal function
• Adequate hepatic function
• Normal range of serum calcium and magnesium
• Agree to use an effective form of contraception during the study and 90 days following the last dose of medication
• Negative urine or serum pregnancy test

You may not qualify if:

• History of prior malignancy within the past 3 years except curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or treated localized prostate cancer
• Prior therapy with gefitinib, erlotinib, cetuximab, ABX-EGF or other specific EGFR inhibitor
• Known hypersensitivity to any components of each drug
• Pregnant or lactating women
• Any other medical condition, including mental illness or substance abuse, deemed by the clinician to be likely to interfere
• Potassium \< 4.0 mEg/L despite supplementation
• Evidence of severe or uncontrolled systemic disease or any concurrent illness that, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
• Clinically significant cardiac event such as myocardial infarction: NYHA classification of heart disease greater than or equal to 2 that, in the opinion of the investigator, increases the risk of ventricular arrhythmia within 3 months before entry; or presence of cardiac disease
• History of arrythmia which is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia
• Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication
• Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
• Presence of left bundle branch block
• QTc with Bazett's correction that is unmeasurable , or greater then 480msec on screening ECG
• Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
• Hypertension not controlled by medical therapy

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• AstraZeneca: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Meyerhardt JA, Ancukiewicz M, Abrams TA, Schrag D, Enzinger PC, Chan JA, Kulke MH, Wolpin BM, Goldstein M, Blaszkowsky L, Zhu AX, Elliott M, Regan E, Jain RK, Duda DG. Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474) as therapy for patients with previously treated metastastic colorectal cancer. PLoS One. 2012;7(6):e38231. doi: 10.1371/journal.pone.0038231. Epub 2012 Jun 12.

  PMID: 22701615 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

vandetanib; Cetuximab; Irinotecan

Condition Hierarchy (Ancestors)

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; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Jeffrey Meyerhardt, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 16, 2007
• Study Start: February 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 4, 2012

Record last verified: 2012-10

Locations

US (3)