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

NCT01255800 | Completed Phase 1 DMC

• 1 other identifier: 11-0109.cc
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities and the recommended dose for phase 2 evaluation of the combination of IPI-926 and cetuximab

  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.

  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.

Secondary Outcomes (1)

• Evaluate the clinical activity of the combination of IPI-926 with cetuximab

  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.

Study Arms (1)

IPI-926 and Cetuximab

EXPERIMENTAL

* 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

Interventions

IPI-926 and Cetuximab DRUG

* Patients will receive Cetuximab IV every week. * Starting on Day 15 of the first cycle, Patients will take IPI-926by mouth every day.

Also known as: brand name: ERBITUX

IPI-926 and Cetuximab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

IPI-926; Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Antonio Jimeno, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2010
• First Posted: December 7, 2010
• Study Start: April 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 31, 2014

Record last verified: 2014-01

Locations

US (1)