NCT03422536

Brief Summary

This randomized phase II trial studies how well ficlatuzumab with or without cetuximab works in treating patients with head and neck squamous cell carcinoma that has come back or spread to other places in the body and resistant to cetuximab treatment. Monoclonal antibodies, such as ficlatuzumab and cetuximab, may block growth signals that lets a tumor cell survive and reproduce, and helps the immune system recognize and fight head and neck squamous cell carcinoma.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Dec 2017

Typical duration for phase_2

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 5, 2017

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 19, 2018

Completed
17 days until next milestone

First Posted

Study publicly available on registry

February 5, 2018

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 29, 2022

Completed
7 days until next milestone

Study Completion

Last participant's last visit for all outcomes

April 5, 2022

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

July 19, 2023

Completed
Last Updated

September 4, 2024

Status Verified

August 1, 2024

Enrollment Period

4.3 years

First QC Date

January 19, 2018

Results QC Date

April 6, 2023

Last Update Submit

August 15, 2024

Conditions

Keywords

Head and Neck CancerOropharyngeal CancerSquamous Cell Carcinomalip carcinomaoral cavity carcinomaHNSCCHead and Neck Squamous Cell CarcinomaAVEO

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival (PFS)

    Will be estimated for each arm using a Kaplan-Meier curve.

    From the date of randomization until the date of progression or death, assessed up to 2 years

Secondary Outcomes (3)

  • Percentage of Participants With Dose Limiting Toxicities or Adverse Events

    Up to 2 years

  • Overall Survival (OS)

    From the date of randomization until the date of death, assessed up to 2 years

  • Overall Response Rate (ORR)

    Up to 2 years

Other Outcomes (5)

  • Change in Quality of Life

    Pre-study (within 4 weeks of study registration) and Week 4, Cycle 2 of Intervention

  • Tumor Biomarker Analysis

    Up to 2 years

  • Genomic Biomarker Analysis

    Up to 2 years

  • +2 more other outcomes

Study Arms (2)

Arm I (ficlatuzumab)

EXPERIMENTAL

Patients receive ficlatuzumab IV over 30-60 minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Ficlatuzumab

Arm II (ficlatuzumab, cetuximab)

EXPERIMENTAL

Patients receive cetuximab IV over 60 -120 minutes and ficlatuzumab IV over 30-60 minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Biological: CetuximabDrug: Ficlatuzumab

Interventions

CetuximabBIOLOGICAL

Given IV

Also known as: Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225
Arm II (ficlatuzumab, cetuximab)

Given IV

Also known as: Anti-HGF Monoclonal Antibody SCH900105, AV-299, SCH 900105
Arm I (ficlatuzumab)Arm II (ficlatuzumab, cetuximab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- Patients must have histologically confirmed HNSCC from any primary site, except nasopharyngeal if World Health Organization (WHO) Type III (non-keratinizing and Epstein-Barr virus (EBV)-positive)).
  • Eligible histologies include:
  • Basaloid, poorly differentiated, and undifferentiated carcinoma histologies.
  • Nasopharyngeal carcinoma, WHO Type I and II (keratinizing, non-EBV positive).
  • Paranasal sinus, lip and external auditory canal sites.
  • Squamous cell carcinoma of unknown primary, clearly related to the head and neck.
  • Note: Documentation of primary site diagnosis must be submitted with the registration request.
  • Patients must have recurrent and/or metastatic disease, fulfilling at least one of the criteria defined below:
  • Incurable disease as assessed by surgical or radiation oncology;
  • Metastatic (M1) disease;
  • Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity. Note: Patients who decline radical surgery are eligible.
  • For patients with oropharyngeal primary site or unknown primary site only: Patients must have known tumoral HPV status (p16). (Acceptable standards include p16 immunohistochemistry (where a tumor is classified as p16-positive when showing diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells) and/or assessment of HPV DNA.) Note: For these subjects, documentation of p16 status must be submitted with the registration packet.
  • Patients must be cetuximab-resistant by fulfilling at least one of the two criteria defined below:
  • Disease persistence or recurrence within 6 months of completing definitive radiotherapy with concurrent cetuximab for locally advanced disease. Induction chemotherapy, if given, may or may not have included cetuximab.
  • Disease progression during, or within 6 months, of cetuximab treatment in the recurrent and/or metastatic setting.
  • +28 more criteria

You may not qualify if:

  • Nasopharyngeal primary site if WHO Type III (non-keratinizing and EBV-positive as established at the local site).
  • History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent.
  • Prior treatment with an HGF/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or tivantinib (ARQ197).
  • Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed.
  • Note: Subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 2 weeks (radiotherapy or surgery).
  • Failure to recover to Grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, immunotherapy, and/or experimental therapy, with the exception of:
  • Alopecia,
  • Grade ≤ 2 peripheral neuropathy,
  • Grade ≤ 2 cetuximab-related rash or other skin changes,
  • Treatment with cetuximab 2 weeks prior to the first dose of study drug. A washout period of 2 weeks from prior cetuximab is required if applicable.
  • Treatment with cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug 3 weeks prior to the first dose of study drug. A washout period of 3 weeks from any prior cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug is required, if applicable.
  • Significant underlying pulmonary disease, including pulmonary hypertension or interstitial pneumonitis.
  • Peripheral edema ≥ Grade 2 per NCI-CTCAE version 4.0.
  • Significant cardiovascular disease, including:
  • Cardiac failure New York Heart Association (NYHA) class III or IV.
  • +18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

  • Bauman JE, Saba NF, Roe D, Bauman JR, Kaczmar J, Bhatia A, Muzaffar J, Julian R, Wang S, Bearelly S, Baker A, Steuer C, Giri A, Burtness B, Centuori S, Caulin C, Klein R, Saboda K, Obara S, Chung CH. Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer. J Clin Oncol. 2023 Aug 1;41(22):3851-3862. doi: 10.1200/JCO.22.01994. Epub 2023 Mar 28.

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and NeckLymphoid Interstitial PneumoniaHead and Neck NeoplasmsOropharyngeal NeoplasmsCarcinoma, Squamous CellLip NeoplasmsMouth Neoplasms

Interventions

Cetuximabficlatuzumab

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms by SitePharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic DiseasesNeoplasms, Squamous CellLip DiseasesMouth Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Rachel Jarrett
Organization
University of Arizona Cancer Center

Study Officials

  • Julie E. Bauman, MD, MPH

    The University of Arizona

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 19, 2018

First Posted

February 5, 2018

Study Start

December 5, 2017

Primary Completion

March 29, 2022

Study Completion

April 5, 2022

Last Updated

September 4, 2024

Results First Posted

July 19, 2023

Record last verified: 2024-08

Locations