Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by University of Pittsburgh.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01488318
First received: November 30, 2011
Last updated: December 6, 2011
Last verified: December 2011
  Purpose

This is a single-arm, non-masked, open-label, Phase II study of cetuximab + dasatinib in recurrent Squamous Cell Carcinoma of The Head and Neck (SCCHN) that has recurred after cetuximab-containing therapy (please see attached schema).

The primary endpoint is ORR. Progression and response will be assessed by RECIST. Patients will continue until PD or intolerable toxicity. Exploratory laboratory correlates are described below.


Condition Intervention Phase
Squamous Cell Carcinoma Of The Head And Neck
Drug: Cetuximab
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial Of Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma of The Head and Neck After Cetuximab-Containing Chemoradiotherapy

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To study efficacy of dasatinib plus cetuximab, as measured by overall response rate (ORR) in order to determine whether or not dasatinib plus cetuximab is recommended for further study in SCCHN.


Secondary Outcome Measures:
  • Time to progression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To estimate time to progression and overall survival.

  • The maximum toxicity for each category of interest in each subject [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    To evaluate the safety of the combination of dasatinib (D) and cetuximab (C) in this patient population. The maximum toxicity for each category of interest will be recorded for each patient and the summary results will be presented in tabular form.


Estimated Enrollment: 37
Study Start Date: October 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cetuximab
    Cetuximab 250 mg/m2 IV weekly after loading dose 400 mg/m2 on cycle 1, day 1
    Other Name: Erbitux
    Drug: Dasatinib
    Dasatinib 150 mg po
Detailed Description:

Patients must have recurrent SCCHN and may have received any number of prior palliative systemic therapies for recurrent disease (without cetuximab or othr EGFR inhibitor). One prior curative regimen (induction, primary or postoperative chemoradiotherapy) should have been given AND all patients should have been exposed to cetuximab as part of prior potentially curative treatment (i.e. with radiotherapy or induction therapy). The last cetuximab dose should be > 3 months. Those who have received a prior Src kinase inhibitor or EGFR inhibitor other than cetuximab are not eligible.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have recurrent SCCHN that has been previously treated with cetuximab as part of potentially curative therapy (i.e. with induction therapy, radiotherapy or chemoradiotherapy). The interval from completion of cetuximab and study treatment should be >3 months.
  • Measurable disease per RECIST 1.1.
  • One prior curative regimen (induction, primary or postoperative chemoradiotherapy) should have been given AND all patients should have been exposed to cetuximab as part of prior potentially curative treatment (i.e. with radiotherapy or induction therapy). The last cetuximab dose should be > 3 months.
  • Unlimited prior treatment with radiation or chemoradiotherapy
  • Any number of prior regimens for recurrent or metastatic SCCHN (i.e. palliative treatment) but without cetuximab or another EGFR inhibitor
  • Age > or equal to 18 years
  • ECOG performance status < or equal to 2
  • Life expectancy of greater than 12 weeks.
  • Patients must have normal organ and marrow function as defined below:
  • absolute neutrophil count > or equal to 1,200/µL
  • platelets > or equal to 100,000/µL
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) < or equal to 2.5 X institutional upper limit normal
  • Creatinine up to 1.5 X normal institutional limits
  • Ability to understand and the willingness to sign a written informed Consent document.
  • Patients should not be taking concomitant medication that are CYP3A4 inducers or potent inhibitors (+++) and should try to avoid taking proton pump inhibitors and H2 antagonists during rest of treatment period. The above medications will be continued only if medically necessary and their use will be noted.
  • 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. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. All WOCBP MUST have a negative pregnancy test prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation.

Exclusion Criteria:

  • Prior treatment with an EGFR inhibitor other than cetuximab at any time
  • Prior treatment with an EGFR inhibitor as part of a regimen for recurrent or metastatic SCCHN.
  • Prior treatment with SFK inhibitor at any time
  • Patients who have not recovered from adverse events due to prior agents. A minimum interval of 3 weeks should have elapsed from prior radiotherapy and/or chemotherapy
  • Patients may not have received an investigational agent within 4 weeks of starting this trial.
  • Patients with untreated brain metastases should be excluded from this clinical trial
  • History of allergic reactions to monoclonal antibodies.
  • Inability to swallow oral medications (unless patients use a feeding tube in which case they are eligible).
  • Uncontrolled angina or uncontrolled 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 (> 450 msec) on the 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01488318

Contacts
Contact: Rita Johnson, RN 412-647-8571 johnsonr1@upmc.edu
Contact: Mary McDonough, BSN 412-623-6793 mcdonoughmf@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: RIta Johnson, RN    412-647-8571    johnsonr1@upmc.edu   
Principal Investigator: Michael Gibson, MD         
Sponsors and Collaborators
University of Pittsburgh
Bristol-Myers Squibb
  More Information

No publications provided by University of Pittsburgh

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01488318     History of Changes
Other Study ID Numbers: 08-034, CA180264
Study First Received: November 30, 2011
Last Updated: December 6, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Cetuximab
Dasatinib
Squamous Cell
Head and Neck
After Cetuximab Containing Chemoradiotherapy
Recurrent

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Cetuximab
Dasatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014