Status:

COMPLETED

Pilot Study of Cetuximab and the Hedgehog Inhibitor IPI-926 in Recurrent Head and Neck Cancer

Lead Sponsor:

University of Colorado, Denver

Conditions:

Recurrent Head and Neck Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

This study will evaluate the clinical activity of the combination of ipilimumab (IPI) -926 in combination with cetuximab in patients with advanced head and neck cancer.

Detailed Description

The purpose of this study is to determine the dose-limiting toxicities and the recommended dose for phase 2 evaluation of the combination of IPI-926 and cetuximab in patients with advanced head and ne...

Eligibility Criteria

Inclusion

  • histologically or cytologically confirmed advanced or metastatic head and neck squamous cell (HNSCC) cancer not amenable to potentially curative resection.
  • Tumor must be amenable to sequential biopsies, and patients must be willing to undergo 3 sequential tumor biopsies.
  • evidence of progression after first-line chemotherapy for locally advanced or recurrent disease. There has to be at least a 4-week period since the last administration of prior therapy and initiation of the current study drugs.
  • Cetuximab is indicated. However, prior therapy with cetuximab (particularly if in the primary setting) is allowed.
  • Presence of measurable target on a CT-scan available for external review, with at least one diameter \>/= 2cm (\>/= 1cm if spiral CT-scan is used for assessment and follow-up).
  • Age \>/= 18 years.
  • The Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>60%, see Appendix A).
  • Life expectancy greater than 12 weeks.
  • Patients must have normal organ and marrow function as defined below:
  • leukocytes \>3,000/μl
  • absolute neutrophil count \>1,500/μl
  • platelets \>100,000/μl
  • total bilirubin \<1.5x Upper limit normal (ULN)
  • Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) \<2.5 X institutional upper limit of normal
  • creatinine \<1.5x ULN OR
  • creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine above ULN.
  • All women of child-bearing potential (WCBP),all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study. Women of child-bearing potential (defined as being less than 1 year post-menopausal) must have a negative serum or urine β human chorionic gonadotropin (βhCG) pregnancy test; and men and women of reproductive potential must agree to practice an effective method of avoiding pregnancy while receiving study drug and for 30 days after the final dose of study drug.

Exclusion

  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Patients receiving any other investigational agents.
  • Patients with known brain metastases.
  • History of allergic reactions attributed to cetuximab or compounds of similar chemical or biologic composition to IPI-926.
  • Patients taking rifampin, St. John's wort, carbamazepine, phenytoin, and phenobarbital are excluded from this trial.
  • Uncontrolled illness including, hypertension, ongoing or active infection, bleeding diathesis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Baseline Fridericia's formula (QTcF) \>450 msec in men or \>470 msec in women.
  • Concurrent treatment with any agent known to prolong the Corrected QT (QTc) interval
  • Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation and meet any of the following criteria are excluded:
  • Have been on a stable dose of anticoagulation for \<1 month
  • Have had a Grade 2, 3 or 4 hemorrhage in the past month
  • Are experiencing continued symptoms from their venous thromboembolic event Patients who have had a venous thromboembolic event but do not meet any of the above three criteria are eligible for participation.
  • History of a seizure within the last 10 years or seizure disorder requiring anti-epileptic medications.
  • Known HIV-positive patients.
  • Therefore, patients taking potent inhibitors or inducers of Cytochrome P450 3A4 (CYP 3A4) should not be enrolled on this study.
  • active infection or systemic use of antibiotic within 72 hours of treatment
  • Cirrhotic liver disease, ongoing alcohol abuse, or chronic active or acute hepatitis

Key Trial Info

Start Date :

April 1 2011

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

December 1 2013

Estimated Enrollment :

9 Patients enrolled

Trial Details

Trial ID

NCT01255800

Start Date

April 1 2011

End Date

December 1 2013

Last Update

January 31 2014

Active Locations (1)

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1

University of Colorado Denver

Denver, Colorado, United States, 80045