Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 6 of 10 for:    Ficlatuzumab

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03422536
Recruitment Status : Recruiting
First Posted : February 5, 2018
Last Update Posted : May 18, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Arizona

Brief Summary:
This randomized phase II trial studies how well ficlatuzumab with or without cetuximab work 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.

Condition or disease Intervention/treatment Phase
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 Biological: Cetuximab Drug: Ficlatuzumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. To describe toxicity and patient-reported quality of life. II. To evaluate response rate and overall survival in both treatment arms. III. To evaluate the relationship between clinical outcomes (PFS, response rate [RR]) and candidate tumoral, genomic, peripheral, and immune biomarkers, including: HGF/cMet, EGFR/EGFR, and EGFR/HER2 dimers; mutations in PIK3CA, PTEN, and HRAS; peripheral serum biomarkers including VeriStrat, HGF, soluble HGF, and IL6; peripheral lymphocyte populations; archived and baseline immune infiltrate.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 5, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Experimental: Arm I (ficlatuzumab)
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
Given IV
Other Names:
  • Anti-HGF Monoclonal Antibody SCH900105
  • AV-299
  • SCH 900105

Experimental: Arm II (ficlatuzumab, cetuximab)
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: Cetuximab
Given IV
Other Names:
  • Chimeric Anti-EGFR Monoclonal Antibody
  • Chimeric MoAb C225
  • Chimeric Monoclonal Antibody C225
  • Erbitux
  • IMC-C225

Drug: Ficlatuzumab
Given IV
Other Names:
  • Anti-HGF Monoclonal Antibody SCH900105
  • AV-299
  • SCH 900105




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: From the date of randomization until the date of progression or death, assessed up to 2 years ]
    Will be estimated for each arm using a Kaplan-Meier curve.


Secondary Outcome Measures :
  1. Biomarker analysis [ Time Frame: Up to 2 years ]
    Will evaluate the relationship between clinical outcomes (progression free survival, response rate) and candidate tumoral, genomic, peripheral, and immune biomarkers, including: HGF/cMet, EGFR/EGFR, and EGFR/HER2 dimers; mutations in PIK3CA, PTEN, and HRAS; peripheral serum biomarkers including VeriStrat, HGF, soluble HGF, and IL6; peripheral lymphocyte populations; archived and baseline immune infiltrate. The relationship between progression-free survival and the candidate biomarkers will be assessed using Cox proportional hazards models. The relationship with clinical response will be assess

  2. Change in quality of life [ Time Frame: Pre-study (within 4 weeks of study registration) and Week 4, Cycle 2 of Intervention ]
    Will be assessed by Foundation for the Accreditation of Cellular Therapy Head and Neck Questionnaire.

  3. Incidence of adverse events [ Time Frame: Up to 2 years ]
    The proportion of dose limiting toxicities in each dosing cohort will be reported, as will the proportion of 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.

  4. Overall survival [ Time Frame: From the date of randomization until the date of death, assessed up to 2 years ]
    Will be estimated for each arm using a Kaplan-Meier curve.

  5. Response rate [ Time Frame: Up to 2 years ]
    Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be tabulated and reported with 95% exact confidence intervals.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Patients must have histologically confirmed HNSCC from any primary site, except nasopharyngeal if WHO Type III (non-keratinizing and 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 or anti-PDL1 mAb, if eligible for immunotherapy in the judgment of the local investigator.

Note: Prior exposure to investigational immunotherapies, including anti-CTLA4, anti-OX40, anti-CD40, anti-CD27, anti-TNFR 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 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).

Exclusion Criteria

  • 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 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:
  • 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 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.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03422536


Contacts
Layout table for location contacts
Contact: Obara Lexi, MS, CIP 520-626-5379 stefanie@email.arizona.edu

Locations
Layout table for location information
United States, Arizona
The University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85719
Contact: Julie E. Bauman, MD, MPH       jebauman@email.arizona.edu   
Contact: Kiley Raica, BS    520-694-9056    kileyraica@email.arizona.edu   
Principal Investigator: Julie E. Bauman, MD, MPH         
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Contact: Elzbieta Nowacki    203-737-7981      
Contact: Elzbieta.nowacki@yale.edu         
Principal Investigator: Aarti Bhatia, MD, MPH         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Alaa Taha    813-745-7025    alaa.taha@moffitt.org   
Principal Investigator: Christine Chung, MD         
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Swathi Chinaranagari    404-686-0239    swathi.chinaranagari@emory.edu   
Principal Investigator: Nabil Saba, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Holly Kilpatrick, RN, BSN    215-728-3511    Holly.Kilpatrick@fccc.edu   
Principal Investigator: Yanis Boumber, MD, PhD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Kristina Godwin, MHA, CCRP    843-792-8876    woodrufk@musc.edu   
Principal Investigator: John Kaczmar, MD         
Sponsors and Collaborators
University of Arizona
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Julie E. Bauman, MD, MPH The University of Arizona
Layout table for additonal information
Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT03422536    
Other Study ID Numbers: 1710965268
NCI-2017-02209 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AV-299-17-117i ( Other Identifier: Aveo Oncology and Biodesix )
1710965268 ( Other Identifier: The University of Arizona Medical Center-University Campus )
P30CA023074 ( U.S. NIH Grant/Contract )
First Posted: February 5, 2018    Key Record Dates
Last Update Posted: May 18, 2020
Last Verified: May 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Arizona:
Head and Neck Cancer
Oropharyngeal Cancer
Squamous Cell Carcinoma
lip carcinoma
oral cavity carcinoma
HNSCC
Head and Neck Squamous Cell Carcinoma
AVEO
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Otorhinolaryngologic Neoplasms
Otorhinolaryngologic Diseases
Pharyngeal Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Antineoplastic Agents, Immunological
Cetuximab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents