Safety Study Of Cetuximab Plus Dasatinib (BMS-354825) in Treating Advanced Solid Malignancies

NCT00388427 | Completed Phase 1 DMC

• 2 other identifiers: 06-038CA180049
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, safety study of cetuximab and differing dose levels of dasatinib in adult patients with advanced solid malignancies. Cetuximab will be administered as an intravenous infusion weekly. Dasatinib will be taken orally, once a day, on a continuous schedule at differing dose levels. The primary objective of this study is to determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors.

Conditions

Malignant Solid Tumour

Keywords

advanced cancer; solid tumor; solid malignancies; phase I

Outcome Measures

Primary Outcomes (1)

• To determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors

  Anticipated completion date December 2008

Secondary Outcomes (5)

• To determine the objective response rate and overall survival in patients enrolled in the study

  Anticipated completion date December 2008

• To evaluate tissue biomarkers that relate to EGFR and Src signaling pathways on baseline tumor tissue and to study their modulation with cetuximab/dasatinib on post-treatment tumor tissue

  Anticipated completion date December 2008

• To measure Src in peripheral blood mononuclear cells (PBMCs) before and after therapy

  Anticipated completion date December 2008

• To evaluate EGFR gene copy number by FISH on baseline tumor tissue

  Anticipated completion date December 2008

• To determine pharmacokinetic parameters of dasatinib in patients with and without feeding tubes

  Anticipated completion date December 2008

Study Arms (1)

Advanced Solid Malignancies

OTHER

Drug: Dasatinib (BMS-354825); Drug: Cetuximab (Erbitux, C225)

Interventions

Dasatinib (BMS-354825) DRUG

100 mg, 150 mg, or 200 mg per dose escalation schedule; continuous oral dosing on Days 1-21 of each 21-day cycle until progression or unacceptable toxicity develops.

Advanced Solid Malignancies

Cetuximab (Erbitux, C225) DRUG

Loading dose of IV 400 mg/m\^2 on Day 1 of Cycle 1; IV 250 mg/m\^2 weekly thereafter each 21-day cycle until progression or unacceptable toxicity develops.

Advanced Solid Malignancies

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 confirmed solid malignancy which is recurrent or metastatic or resistant to therapy. Patients w/plan of surgery for recurrent disease post cetuximab/dasatinib are eligible providing that they receive at least 2 cycles of therapy and provide baseline and post-treatment tumor tissue for correlatives.
• Any number of prior regimens but no prior EGFR or src inhibitors.
• Age greater or equal to 18 years.
• ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
• Life expectancy greater than 12 weeks.
• Patients must have normal organ and marrow function:
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to 1,500/mcL
• platelets greater than or equal to 100,000/mcL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
• creatinine up to 1.5 x normal institutional limits
• Ability to understand and the willingness to sign a written informed Consent document.
• No concomitant medication that are CYP3A4 inducers or potent inhibitors and should not take proton pump inhibitors and H2 antagonists in the first cycle of therapy and should try to avoid taking proton pump inhibitors and H2 antagonists during rest of treatment period.
• Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. All WOCBP must have a negative pregnancy test prior to first receiving investigational product.

You may not qualify if:

• Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Any other concurrent investigational agents.
• Patients w/ untreated brain metastases. However, patients who have stable brain disease (should be off corticosteroids) at least 4 weeks after completion of appropriate therapy are eligible.
• History of allergic reaction to monoclonal antibodies.
• Inability to swallow oral medications unless patients use a feeding tube.
• Uncontrolled angina or hypertension or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
• Prolonged QTc interval on pre-entry electrocardiogram (greater than 450 msec) on both the Fridericia and Bazett's correction.
• Diagnosed or suspected congenital long QT syndrome.
• Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
• Any other uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
• HIV-positive patients receiving combination antiretroviral therapy.

Sponsors & Collaborators

• University of Pittsburgh: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Pittsburgh Cancer Institute - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

Dasatinib; Cetuximab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Edward Chu, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 13, 2006
• First Posted: October 16, 2006
• Study Start: June 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: February 1, 2013
• Last Updated: May 28, 2015

Record last verified: 2014-01

Locations

US (1)