Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma

NCT01488318 | Terminated Phase 2 Results DMC

• 2 other identifiers: 08-034CA180264
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Squamous Cell Carcinoma Of The Head And Neck

Keywords

Cetuximab; Dasatinib; Squamous Cell; Head and Neck; After Cetuximab Containing Chemoradiotherapy; Recurrent; Metastatic

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 36 months

• Response to Treatment

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

  Up to 36 months

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  Up to 36 months

• Overall Survival (OS)

  Up to 60 months

Study Arms (1)

CETUXIMAB AND DASATINIB

EXPERIMENTAL

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; Drug: Dasatinib

Interventions

Cetuximab DRUG

Cetuximab 250 mg/m2 IV weekly after loading dose 400 mg/m2 on cycle 1, day 1

Also known as: Erbitux

CETUXIMAB AND DASATINIB

Dasatinib DRUG

Dasatinib 150 mg po

CETUXIMAB AND DASATINIB

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Julie E. Bauman, MD, MPH: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (2)

• 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.

  PMID: 28559019 DERIVED

• 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.

  PMID: 24727329 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Recurrence; Neoplasm Metastasis

Interventions

Cetuximab; Dasatinib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Barbara Stadterman, Regulatory Supervisor
• Organization: University of Pittsburgh Cancer Institute

stadtermanbm@upmc.edu

414-647-5554

Study Officials

• Julie Bauman

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 30, 2011
• First Posted: December 8, 2011
• Study Start: September 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: August 1, 2016
• Last Updated: January 5, 2018
• Results First Posted: January 5, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)