AzTrials
AzTrials

Head and Neck Basaloid CarcinomaPhase 2NCT03422536

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

A Phase 2 study testing Cetuximab and Ficlatuzumab in people with Head and Neck Basaloid Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by University of Arizona at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab and Ficlatuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
6 sitesUnited States
Study dates
5 Dec 2017to 5 Apr 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 43Show fewer
  • 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.
  • Patients must consent to a research biopsy of tumor tissue at baseline, for conduct of correlative studies. In cases where a fresh biopsy is not feasible (i.e., if an accessible tumor site cannot be biopsied with acceptable clinical risk), archival tissue may be submitted instead, after discussion with and approval by the Sponsor-Investigator.
  • Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1 (see section 6) per scan within 28 days prior to registration.
  • Patients must have adequate electrolytes, liver, renal, and hematology function as defined below within 28 days of registration:
  • Absolute neutrophil count (ANC) ≥ 1500/mm3
  • Platelet count (PLT) ≥ 75,000/mm3
  • Creatinine clearance ≥ 30 mL/min per estimated by the Cockraft-Gault formula:
  • Calculated Creatinine Clearance = [(140-age) X (actual body weight in kg) X (0.85 if female)]/(72 X serum creatinine)
  • Total bilirubin ≤ 1.5 times upper-limit of normal (ULN)
  • AST (aspartate aminotransferase) ≤ 3 times ULN
  • ALT (alanine aminotransferase) ≤ 3 times ULN
  • Magnesium ≥ 1.2 mg/dL or 0.5 mmol/L
  • Corrected Calcium ≥ 8.0 mg/dL or 2.0 mmol/L
  • Potassium ≥ 3.0 mmol/L (Note: Patients may be supplemented to achieve acceptable electrolyte values.)
  • Serum albumin ≥ 25 g/L (≥ 2.5 g/dL)
  • Patients must sign written informed consent prior to beginning study screening procedures. Patients must have the ability to understand and the willingness to sign a written informed consent document.
  • Women of child-bearing potential (WOCBP) must agree to have a pregnancy test within 14 days prior to registration and a repeated test within 3 days of the first dose of ficlatuzumab.
  • Patients must agree to use highly effective contraceptive measures while on study and for 60 days after the last dose of study drug. This includes: Men of reproductive potential AND women of childbearing potential.
  • Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).

Who cannot join

  • 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:
Show all 37Show fewer
  • 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:
  • Excised and cured non-melanoma skin cancer,
  • Carcinoma in situ of breast or cervix,
  • Superficial bladder cancer,
  • Stage I differentiated thyroid cancer that is resected or observed,
  • pT1a /pT1b prostate cancer comprising < 5% of resected tissue with normal prostate specific antigen (PSA) since resection, or
  • cT1a/cT1b prostate cancer treated with brachytherapy or external beam radiation therapy with normal PSA since radiation.
  • Not completely recovered from any previous surgery. Note: Complete recovery is in the opinion of the treating investigator. Consult the Sponsor-Investigator, if needed.
  • Active systemic infection requiring systemic antibiotics or antifungals within 7 days prior to first dose of study drug, except tetracycline family antibiotics (tetracycline, doxycycline, minocycline) administered for the management of cetuximab-related rash may be continued per the Investigator's judgment.
  • Note: Active topical infections (for example oral thrush) do not exclude a subject even if treated with systemic antibiotics or systemic antifungals.
  • History of severe infusion reaction to cetuximab or a monoclonal antibody.
  • Known to be Human immunodeficiency virus (HIV) positive. Note: HIV testing is not required for entry into this protocol.
  • Women who are pregnant or breastfeeding. (A negative urine pregnancy test must be confirmed within 14 days of registration and repeated within 3 days of the first dose of study drug.)

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Yale Cancer Center

    New Haven, Connecticut, 06520

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85719

Other trials in United States

About this study

Official title: A Randomized, Phase II Study of Ficlatuzumab With or Without Cetuximab in Patients With Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the efficacy of ficlatuzumab, with or without concurrent cetuximab, in patients with cetuximab-resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) as measured by progression-free survival (PFS).

SECONDARY OBJECTIVES:

  1. To describe toxicity. II. To evaluate response rate and overall survival in both treatment arms.

EXPLORATORY OBJECTIVES I. To describe patient reported quality of life

II. To evaluate the relationship between clinical outcomes (Progression-Free Survival and Response Rate) and candidate tumoral, genomic, peripheral, and immune biomarkers, potentially including but not limited to:

  • Tumor Hepatocyte Growth Factor (HGF) and tyrosine-protein kinase Met (cMet) expression
  • mutations in PIK3CA, phosphatase and tensin homolog (PTEN), and HumanRAS proto-oncogene (HRAS);
  • peripheral serum biomarkers including HGF, soluble HGF, and interleukin 6 (IL6);
  • peripheral lymphocyte populations;
  • archived and baseline immune infiltrate;
  • tumor Human Papilloma Virus (HPV) status.

OUTLINE: Patients are randomized into 1 of 2 arms.

Arm I: Patients receive ficlatuzumab intravenously (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.

Arm II: 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.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Being tested
Cetuximab, Ficlatuzumab
Keywords
Head and Neck Cancer, Oropharyngeal Cancer, Squamous Cell Carcinoma, lip carcinoma, oral cavity carcinoma, HNSCC, Head and Neck Squamous Cell Carcinoma, AVEO
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Lymphoid Interstitial Pneumonia, Head and Neck Neoplasms, Oropharyngeal Neoplasms, Carcinoma, Squamous Cell, Lip Neoplasms, Mouth Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabBiological

    Also called Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux

    Given IV

  • FiclatuzumabDrug

    Also called Anti-HGF Monoclonal Antibody SCH900105, AV-299, SCH 900105

    Given IV

Study groups in NCT03422536
Study groupRoleWhat they receive
Arm I (ficlatuzumab)ExperimentalPatients 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.
Receives: Drug: Ficlatuzumab
Arm II (ficlatuzumab, cetuximab)ExperimentalPatients 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.
Receives: Biological: Cetuximab; Drug: Ficlatuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

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

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

Secondary outcomes (3)

  1. Percentage of Participants With Dose Limiting Toxicities or Adverse Events

    The percentage of participants with dose limiting toxicities in each dosing cohort will be reported, as will the percentage of participants with adverse events in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events version 4 grading criteria. Will be tabulated and reported with 95% exact confidence intervals.

    Measured: Up to 2 years

  2. Overall Survival (OS)

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

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

  3. Overall Response Rate (ORR)

    Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST v1.1) for target lesions and assessed by CT/MRI w/ contrast: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), the regression of all Target lesions (the sum) by 30% with no progression of Non-targets or presence of new lesion; Overall Response (OR) = CR + PR. Will be tabulated and reported with 95% exact confidence intervals.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2018
  2. Study start5 Dec 2017
  3. Primary completion29 Mar 2022
  4. Study completion5 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03422536
Sponsor's protocol ID
1710965268
Other IDs
NCI-2017-02209, AV-299-17-117i, 1710965268, P30CA023074
Status last verified
Aug 2024
First submitted
19 Jan 2018
Last updated
4 Sep 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36977289

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cetuximab and Ficlatuzumab in people with Head and Neck Basaloid Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by University of Arizona at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 43 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: From the date of randomization until the date of progression or death, assessed up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03422536, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in