Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma

December 7, 2017 updated by: Julie E. Bauman, MD, MPH

Phase II Trial of Cetuximab and Dasatinib in Patients With Cetuximab-resistant, Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck and Low Serum IL-6

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 12-week PFS.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.Those who have received a prior Src kinase inhibitor or EGFR inhibitor other than cetuximab are not eligible.

Patients will be tested for serum IL-6. If IL-6 is detectable, the patient will be ineligible. If IL-6 is not detected, the patient will be eligible for the study. Subjects more than 2 weeks post last dose of Cetuximab will receive an initial loading dose 400 mg/m2 on cycle 1, day 1. Subjects who have received Cetuximab within 2 weeks of starting study will start Cycle 1 with dose of 250 mg/m2. Dasatinib will start 3 days after initial cetuximab study dose on cycle 1 (i.e cycle 1, day 4), and continue without interruption.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion:

  • Patients must have metastatic and/or recurrent SCCHN that has been previously treated with cetuximab.
  • Undetectable baseline serum IL-6 NOTE : This eligibility criterion applies only to patients enrolling to the second, biomarker-enrichment stage of the trial.
  • Measurable disease per RECIST 1.1.
  • Unlimited prior treatment with radiation or chemoradiotherapy
  • Any number of prior regimens for recurrent or metastatic SCCHN (i.e. palliative treatment) including cetuximab or other EGFR inhibitor
  • Age >18 years
  • ECOG performance status <2 (Karnofsky >60%, see Appendix A).
  • Life expectancy of greater than 12 weeks.

  • Patients must have normal organ and marrow function as defined below:

    1. absolute neutrophil count >1,200/µL
    2. platelets >100,000/µL
    3. total bilirubin within normal institutional limits
    4. AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal
    5. 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:

  • Patients who have not recovered from adverse events due to prior agents. A minimum interval of 3 weeks should have elapsed from prior chemotherapy other than cetuximab. A minimum of 12 weeks should have elapsed from prior definitive radiotherapy, and a minimum of 1 week should have elapsed from prior palliative radiotherapy.
  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CETUXIMAB AND DASATINIB

Cetuximab on a standard weekly schedule (see Section 6.2). Group 1 (subjects more than 2 weeks post last dose of Cetuximab): Loading dose of 400 mg/m2 on cycle 1, day 1 then 250 mg/m2 IV weekly.

Group 2 (subjects last Cetuximab treatment within 2 weeks): Cycle 1 will start at a dose of 250 mg/m2 Dasatinib 150 mg once daily without interruption. On the FIRST cycle (1 cycle is 3 weeks) dasatinib will start 3 days after the cetuximab loading dose (i.e. cycle 1, day 4) to avoid headache as shown on the previous phase I trial.

Treatment will continue until progression.
Drug: Cetuximab
Cetuximab 250 mg/m2 IV weekly after loading dose 400 mg/m2 on cycle 1, day 1
Other Names:
  • Erbitux
Drug: Dasatinib
Dasatinib 150 mg po

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Up to 36 months
Number of patients experiencing a Complete Response (CR) + Partial Response (PR) to study treatment / Total number of evaluable patients, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Up to 36 months
Response to Treatment
Time Frame: Up to 36 months
Response of evaluable patients to treatment, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Up to 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: Up to 36 months
Up to 36 months
Overall Survival (OS)
Time Frame: Up to 60 months
From date of entry into the study until the date of death from any cause, assessed up to 60 months.
Up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Julie E. Bauman, MD, MPH

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Julie Bauman, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2011

Primary Completion (ACTUAL)

January 1, 2016

Study Completion (ACTUAL)

August 1, 2016

Study Registration Dates

First Submitted

November 30, 2011

First Submitted That Met QC Criteria

December 6, 2011

First Posted (ESTIMATE)

December 8, 2011

Study Record Updates

Last Update Posted (ACTUAL)

January 5, 2018

Last Update Submitted That Met QC Criteria

December 7, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-034
  • CA180264 (OTHER: BMS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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