Ficlatuzumab w/wo Cetuximab in Patients w/Cetuximab-Resistant, Recurrent or Metastatic Head/Neck Squamous Cell Carcinoma

Completed · Phase 2

Conditions studied: Head and Neck Basaloid Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma of Unknown Primary Origin, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage IV Oropharyngeal Squamous Cell Carcinoma, Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma, Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma, Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage IVA Oropharyngeal Squamous Cell Carcinoma, Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma, Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma, Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage IVB Oropharyngeal Squamous Cell Carcinoma, Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma, Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma, Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage IVC Oropharyngeal Squamous Cell Carcinoma, Head and Neck Cancer, Oropharyngeal Cancer, HNSCC, Stage IV Lip and Oral Cavity Squamous Cell Carcinoma

In brief

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.

Key facts

Study ID

NCT03422536

Run by

University of Arizona

People needed

78

Starts

2017-12-05

Expected to finish

2022-04-05

Last updated by the study team

2024-09-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Note: Prior cetuximab exposure may have occurred in any line of therapy (first line, second line, etc.) and is not required to be the most recent therapy received.
• Patients must be platinum-resistant or platinum-ineligible by fulfilling at least one of the three criteria defined below:
• Disease persistence or recurrence within 6 months of completing definitive radiotherapy for locally advanced disease, where platinum chemotherapy was administered as a component of induction and/or concurrent systemic treatment.
• Disease progression during, or within 6 months, of treatment with platinum chemotherapy (e.g., carboplatin or cisplatin) in the recurrent and/or metastatic setting.
• The patient is not an acceptable candidate for platinum chemotherapy due to medical comorbidities, in the judgment of the local investigator.
• Note: Prior platinum exposure may have occurred in any line of therapy (first line, second line, etc.) and is not required to be the most recent therapy received.
• Patients must have prior exposure to an anti-PD1 (programmed cell death protein 1) or anti-PDL1 (programmed cell death ligand 1) monoclonal antibody (mAb), if eligible for immunotherapy in the judgment of the local investigator.
• Note: Prior exposure to investigational immunotherapies, including anti-CTLA4 (cytotoxic T-lymphocyte-associated antigen 4), anti-OX40, anti-CD40 (cluster of differentiation 40), anti-CD27, anti-TNFR (tumor necrosis factor receptor) antibodies or other investigational immunotherapies, is acceptable.
• Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 at time of informed consent (see Appendix B).
• Patients must be age ≥ 18 years.

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,
• Hypomagnesemia (acceptable values detailed in the exclusion criteria below),
• Hypokalemia (acceptable values detailed in the exclusion criteria below), and
• The acceptable ANC and PLT inclusion criteria values above.
• 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.
• Myocardial infarction within 6 months prior to registration.
• Severe or unstable angina within 6 months prior to registration.
• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation).
• Cardiac arrhythmia requiring anti-arrhythmic medication(s). (Beta-blockers, calcium channel blockers, and digoxin administered for the purpose of rate control of supraventricular tachycardia, including atrial fibrillation and atrial flutter, are not classified as anti-arrhythmic medications for purposes of trial eligibility.)
• Significant thrombotic or embolic events within 28 days prior to registration. (Significant thrombotic or embolic events include but are not limited to stroke or transient ischemic attack (TIA). Catheter-related thrombosis is not a cause for exclusion. Diagnosis of deep vein thrombosis or pulmonary embolism is allowed if it occurred > 28 days prior to registration and the patient is asymptomatic and stable on anti-coagulation therapy.)
• Any other medical condition (e.g., alcohol abuse) or psychiatric condition that, in the opinion of the local Investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results.
• History of second malignancy within 2 years prior to registration except:

Where it is running

• The University of Arizona Cancer Center — Tucson, Arizona, United States
• Yale Cancer Center — New Haven, Connecticut, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Winship Cancer Institute of Emory University — Atlanta, Georgia, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States

Full record on ClinicalTrials.gov

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