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Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma

Primary Purpose

Squamous Cell Carcinoma Of The Head And Neck

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cetuximab
Dasatinib
Sponsored by
Julie E. Bauman, MD, MPH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma Of The Head And Neck focused on measuring Cetuximab, Dasatinib, Squamous Cell, Head and Neck, After Cetuximab Containing Chemoradiotherapy, Recurrent, Metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • University of Pittsburgh Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CETUXIMAB AND DASATINIB

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
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.
Response to Treatment
Response of evaluable patients to treatment, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Progression-free Survival (PFS)
Overall Survival (OS)
From date of entry into the study until the date of death from any cause, assessed up to 60 months.

Full Information

First Posted
November 30, 2011
Last Updated
December 7, 2017
Sponsor
Julie E. Bauman, MD, MPH
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01488318
Brief Title
Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
PI leaving the institution
Study Start Date
September 2011 (Actual)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Julie E. Bauman, MD, MPH
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma Of The Head And Neck
Keywords
Cetuximab, Dasatinib, Squamous Cell, Head and Neck, After Cetuximab Containing Chemoradiotherapy, Recurrent, Metastatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CETUXIMAB AND DASATINIB
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Cetuximab 250 mg/m2 IV weekly after loading dose 400 mg/m2 on cycle 1, day 1
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Intervention Description
Dasatinib 150 mg po
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 36 months
Title
Response to Treatment
Description
Response of evaluable patients to treatment, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time Frame
Up to 36 months
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Time Frame
Up to 36 months
Title
Overall Survival (OS)
Description
From date of entry into the study until the date of death from any cause, assessed up to 60 months.
Time Frame
Up to 60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: absolute neutrophil count >1,200/µL platelets >100,000/µL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) < 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. 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie Bauman
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28559019
Citation
Stabile LP, Egloff AM, Gibson MK, Gooding WE, Ohr J, Zhou P, Rothenberger NJ, Wang L, Geiger JL, Flaherty JT, Grandis JR, Bauman JE. IL6 is associated with response to dasatinib and cetuximab: Phase II clinical trial with mechanistic correlatives in cetuximab-resistant head and neck cancer. Oral Oncol. 2017 Jun;69:38-45. doi: 10.1016/j.oraloncology.2017.03.011. Epub 2017 Apr 9.
Results Reference
derived
PubMed Identifier
24727329
Citation
Gross ND, Bauman JE, Gooding WE, Denq W, Thomas SM, Wang L, Chiosea S, Hood BL, Flint MS, Sun M, Conrads TP, Ferris RL, Johnson JT, Kim S, Argiris A, Wirth L, Nikiforova MN, Siegfried JM, Grandis JR. Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer. Clin Cancer Res. 2014 Jun 15;20(12):3289-98. doi: 10.1158/1078-0432.CCR-13-3360. Epub 2014 Apr 11.
Results Reference
derived

Learn more about this trial

Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma

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