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

This study has been completed.
Sponsor:
Collaborator:
University of Colorado Hospital
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01255800
First received: December 6, 2010
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Head and Neck Cancer
Drug: IPI-926 and Cetuximab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Cetuximab and the Hedgehog Inhibitor IPI-926 in Recurrent Head and Neck Cancer: a Rational Anti-Cancer Stem Cell Combination.

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Dose-limiting toxicities and the recommended dose for phase 2 evaluation of the combination of IPI-926 and cetuximab [ Time Frame: The first 3 patients enrolled will receive the first dose level. A full safety evaluation will be conducted after 6 weeks of therapy. This will continue until a MTD is determined. ] [ Designated as safety issue: Yes ]
    Cohorts of 3. The first cohort will receive dose level 1. A full safety evaluation will be conducted after 6 weeks. If 0/3 have a Dose limiting toxicity (DLT), then a new cohort will receive the next dose level. If 1/3 have DLT then 3 more patients will be treated at this dose level. If none has DLT then the next dose level will be administered to the next cohort; otherwise the inferior dose level will be considered the maximum tolerated dose (MTD). If 2/3 have a DLT, then the inferior dose level will be considered the MTD. In the event that the initial dose level 1 is not tolerated, a level -1 has been defined for assessment.


Secondary Outcome Measures:
  • Evaluate the clinical activity of the combination of IPI-926 with cetuximab [ Time Frame: Patients will continue to receive treatment as long as there is evidence that their tumor is not growing and they are not experiencing any unacceptable side effects. ] [ Designated as safety issue: Yes ]
    Obtaining tumor biopsies at baseline, after 2 weeks of cetuximab, and after 3-4 weeks of dual therapy will enable testing our hypotheses. Patients will be assessed by standard criteria. CTs will also be conducted at the end of first cycle to assess disease progression. Confirmatory scans will also be obtained 4 weeks following initial documentation of an objective response. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [The Journal of the National Cancer Institute (JNCI) 92(3):205-216, 2000].


Enrollment: 9
Study Start Date: April 2011
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPI-926 and Cetuximab
  • Patients will receive Cetuximab IV every week.
  • Starting on Day 15 of the first cycle, Patients will take the study drug by mouth every day.
Drug: IPI-926 and Cetuximab
  • Patients will receive Cetuximab IV every week.
  • Starting on Day 15 of the first cycle, Patients will take IPI-926by mouth every day.
Other Name: brand name: ERBITUX

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 neck cancer.

  Eligibility

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

Inclusion Criteria:

  • 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 Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01255800

Locations
United States, Colorado
University of Colorado Denver
Denver, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
University of Colorado Hospital
Investigators
Principal Investigator: Antonio Jimeno, MD, PhD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01255800     History of Changes
Other Study ID Numbers: 11-0109.cc
Study First Received: December 6, 2010
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014