Ignite Creation Date:
2024-05-06 @ 3:22 AM
Last Modification Date:
2024-10-26 @ 11:33 AM
Study NCT ID:
NCT02277197
Status:
COMPLETED
Last Update Posted:
2019-04-18
First Post:
2014-10-25
Brief Title:
Ficlatuzumab and Cetuximab in RecurrentMetastatic Head and Neck Squamous Cell Carcinoma HNSCC
Sponsor:
James J Lee
Organization:
University of Pittsburgh
Study Overview
Official Title:
A Phase 1b Study of Ficlatuzumab and Cetuximab in RecurrentMetastatic Head and Neck Squamous Cell Carcinoma With Biomarker Correlatives
Status:
COMPLETED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The epidermal growth factor receptor EGFR is both oncogene and prognostic biomarker in head and neck squamous cell carcinoma HNSCC EGFRs functional importance in HNSCC resulted in development of the first molecularly targeted strategy the anti-EGFR monoclonal antibody cetuximab Given the lack of therapeutic options for patients with recurrentmetastatic HNSCC after failure of cetuximab there is strong scientific interest in understanding resistance in order to identify new therapies for this population A possible resistance mechanism to anti-EGFR therapy in HNSCC is primary or compensatory activation of alternate growth factor receptors including c-Met The MET oncogene encodes c-Met an RTK bound exclusively by the ligand hepatocyte growth factor HGF The HGFc-Met signaling pathway converges with the EGFR network at both the PI3KAkt and MAPK nodes Laboratory data suggest the ability for reciprocal compensation between EGFR and c-Met We hypothesize that HGFc-Met pathway inhibition may overcome resistance to cetuximab in patients with HNSCC such as those with clinical cetuximab resistance
Ficlatuzumab AV-299 is a humanized HGF-inhibitory immunoglobulin G1 IgG1 monoclonal antibody The primary objective of this phase 1b study is to find the recommended phase II dose RP2D of the combination of ficlatuzumab and cetuximab in patients with recurrentmetastaticHNSCC The dose-finding study design will follow a Narayana k-in-a-row design with k set to 2 to target a 33 rate of dose-limiting toxicity DLT In the dose-finding phase a total of 8 patients will be treated if no DLTs are observed or 14 patients if at least one DLT occurs An expansion cohort will then proceed at RP2D until 12 patients have been treated at that dose level with the combination of ficlatuzumab and cetuximab We will evaluate biomarkers of HGFcMet pathway activation in baseline tissue plasma and immune cells for a preliminary relationship with clinical activity
Ficlatuzumab AV-299 is a humanized HGF-inhibitory immunoglobulin G1 IgG1 monoclonal antibody The primary objective of this phase 1b study is to find the recommended phase II dose RP2D of the combination of ficlatuzumab and cetuximab in patients with recurrentmetastaticHNSCC The dose-finding study design will follow a Narayana k-in-a-row design with k set to 2 to target a 33 rate of dose-limiting toxicity DLT In the dose-finding phase a total of 8 patients will be treated if no DLTs are observed or 14 patients if at least one DLT occurs An expansion cohort will then proceed at RP2D until 12 patients have been treated at that dose level with the combination of ficlatuzumab and cetuximab We will evaluate biomarkers of HGFcMet pathway activation in baseline tissue plasma and immune cells for a preliminary relationship with clinical activity
Detailed Description:
This is a phase 1b single arm open-labeled study of ficlatuzumab and cetuximab in recurrentmetastatic HNSCC with biomarker correlatives The primary objective of this study is to establish the recommended-for-phase II dose RP2D of the combination of ficlatuzumab and Cetuximab In the absence of treatment delays due to adverse events treatment may continue until disease progression or until one of the following criteria applies
Disease progression
Intercurrent illness that prevents further administration of treatment
Unacceptable adverse events
Patient decides to withdraw from the study or
General or specific changes in the patients condition render the patient unacceptable for further treatment in the judgment of the investigator
After progressive disease subjects will be followed for survival every 3 months for 2 years
Cetuximab and ficlatuzumab are administered every other week on day 1 and 15 of a 28-day cycle Ficlatuzumab will be administered as an IV infusion over 30-60 minutes10 mgkg every 2 weeks on the same day as the first dose of cetuximab Ficlatuzumab will be administered 30-60 minutes after the completion of the cetuximab infusion Cetuximab will be administered prior to ficlatuzumab as an IV infusion The first dose will be administered over 120 minutes 15 minutes Subsequent doses may be infused over 60 minutes 15 minutesThe starting dose of cetuximab dose tier 1 will be 500 mgm2 every 2 weeks
Subjects will be monitored for adverse events and toxicity during study treatment and for 30 days after last dose of ficlatuzumab Blood will be drawn for correlative studies at baseline and at the end of every even cycle Prior to initiation of protocol treatment patients will undergo a mandatory research biopsy
Disease progression
Intercurrent illness that prevents further administration of treatment
Unacceptable adverse events
Patient decides to withdraw from the study or
General or specific changes in the patients condition render the patient unacceptable for further treatment in the judgment of the investigator
After progressive disease subjects will be followed for survival every 3 months for 2 years
Cetuximab and ficlatuzumab are administered every other week on day 1 and 15 of a 28-day cycle Ficlatuzumab will be administered as an IV infusion over 30-60 minutes10 mgkg every 2 weeks on the same day as the first dose of cetuximab Ficlatuzumab will be administered 30-60 minutes after the completion of the cetuximab infusion Cetuximab will be administered prior to ficlatuzumab as an IV infusion The first dose will be administered over 120 minutes 15 minutes Subsequent doses may be infused over 60 minutes 15 minutesThe starting dose of cetuximab dose tier 1 will be 500 mgm2 every 2 weeks
Subjects will be monitored for adverse events and toxicity during study treatment and for 30 days after last dose of ficlatuzumab Blood will be drawn for correlative studies at baseline and at the end of every even cycle Prior to initiation of protocol treatment patients will undergo a mandatory research biopsy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None