Symptoms and General Pathology

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Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

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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

Disease Attributes

Neoplasms, Squamous Cell

Otorhinolaryngologic Neoplasms

Otorhinolaryngologic Diseases

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Pharyngeal Diseases

Stomatognathic Diseases

Oral Squamous Cell Carcinoma

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Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Cetuximab

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

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.

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.

Ficlatuzumab

Julie E. Bauman, MD, MPH

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.

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. 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.

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

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

Will be assessed by Foundation for the Accreditation of Cellular Therapy Head and Neck Questionnaire.

Will evaluate the relationship between clinical outcomes (progression free survival, response rate) and candidate tumoral biomarkers: Tumor HGF and cMET expression. The relationship with clinical response will be assessed.

To evaluate the relationship between clinical outcomes (Progression-Free Survival and Response Rate) and candidate genomic biomarkers: mutations in PIK3CA, PTEN, and HRAS

Will evaluate the relationship between clinical outcomes (progression free survival, response rate) and candidate peripheral biomarkers: peripheral serum biomarkers including HGF, soluble HGF, and IL6; peripheral lymphocyte populations. The relationship with clinical response will be assessed.

Will evaluate the relationship between clinical outcomes (progression free survival, response rate) and candidate immune biomarkers: archived and baseline immune filtrate; tumor HPV status. The relationship with clinical response will be assessed.

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

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.

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.

National Cancer Institute (NCI)

University of Arizona

Only AEs meeting one of the below criteria were collected:

* Any AE that is Grade 3 or \>
* Any AE that results in submission of a serious adverse event(SAE)
* Any intolerable Grade 2 AE
* Any Grade AE resulting in a dose reduction of study drugs
* Any Grade 2 laboratory or vital sign values that are deemed clinically significant by the treating investigator
* Any Grade AE in the following categories:

  * Rash
  * Diarrhea
  * Edema, peripheral
  * Edema, head, face and neck
  * Hypoalbuminemia

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.

Ficlatuzumab: Given IV

Arm I (Ficlatuzumab)

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.

Cetuximab: Given IV

Ficlatuzumab: Given IV

Arm II (Ficlatuzumab, Cetuximab)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Oral Cavity

Oropharynx

Larynx

Nasopharynx

Paranasal sinus

External auditory canal

Unknown primary

Primary Site

Positive

Negative

HPV status

Median months since last cetuximab treatment

History of platinum

History of anti-PD-1 (checkpoint protein) monoclonal antibody (mAb) treatment

Asymptomatic (0) - Fully active, able to carry on all pre-disease performance without restriction

Symptomatic (1) - restricted in physically strenuous activity but able to carry out light work

Eastern Cooperative Oncology Group Performance Status (ECOG- PS)

Rachel Jarrett

Progression Free Survival (PFS)

hypoalbuminemia

Edema

Acneiform rash

Pneumonitis

Percentage of Participants With Dose Limiting Toxicities or Adverse Events

Overall Survival (OS)

Overall Response Rate (ORR)

Change in Quality of Life

c-Met positivity was compared across groups: HPV+ vs HPV-

Post-hoc comparison of progression free survival (PFS) in cMet positive vs. c-Met negative patients.

Post hoc comparison of PFS in the combination arm by HPV subgroup, adjusted for prognostic factors marginally associated with HPV status (P , .10), was assessed using Cox proportional hazards models. Here we are looking at cMet positivity in HPV- patients in the combination arm.

Post hoc comparison of PFS in the combination arm by HPV subgroup, adjusted for prognostic factors marginally associated with HPV status (P , .10), was assessed using Cox proportional hazards models. Here we are looking at cMet positivity in HPV+ patients in the combination arm.

Post-hoc comparison of progression free survival (PFS) in HGF positive vs. HGF negative patients.

Post hoc comparison of PFS in the combination arm by HPV subgroup, adjusted for prognostic factors marginally associated with HPV status (P , .10), was assessed using Cox proportional hazards models. Here we are looking at HGF expression in HPV- patients in the combination arm.

Post hoc comparison of PFS in the combination arm by HPV subgroup, adjusted for prognostic factors marginally associated with HPV status (P \< .10), was assessed using Cox proportional hazards models. Here we are looking at HGF expression in HPV+ patients in the combination arm.

HPV-negative patients

HPV-positive patients

HGF - HPV-positive

HGF - HPV-negative

C-met positive in HPV-negative patients

C-met positive in HPV-positive patients

Exploratory biomarker analysis was only conducted for the combination arm. The monotherapy arm closed for futility. It would be costly and would not add value to study biomarkers in the setting of an inactive agent to perform analyses for the monotherapy arm thus the limited funds available for correlatives were allocated to the combination arm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ficlatuzumab w/wo Cetuximab in Patients w/Cetuximab-Resistant, Recurrent or Metastatic Head/Neck Squamous Cell Carcinoma	NCT03422536	Head and Neck B... Recurrent Head ... Recurrent Oroph... Squamous Cell C... Stage IV Squamo... Stage IV Squamo... Stage IV Nasoph... Stage IV Oropha... Stage IVA Lip a... Stage IVA Nasal... Stage IVA Nasop... Stage IVA Oroph... Stage IVB Lip a... Stage IVB Nasal... Stage IVB Nasop... Stage IVB Oroph... Stage IVC Lip a... Stage IVC Nasal... Stage IVC Nasop... Stage IVC Oroph... Head and Neck C... Oropharyngeal C... HNSCC Stage IV Lip an...	Cetuximab Ficlatuzumab	18 Years -	University of Arizona
Ficlatuzumab w/wo Cetuximab in Patients w/Cetuximab-Resistant, Recurrent or Metastatic Head/Neck Squamous Cell Carcinoma	NCT03422536	Head and Neck B... Recurrent Head ... Recurrent Oroph... Squamous Cell C... Stage IV Squamo... Stage IV Squamo... Stage IV Nasoph... Stage IV Oropha... Stage IVA Lip a... Stage IVA Nasal... Stage IVA Nasop... Stage IVA Oroph... Stage IVB Lip a... Stage IVB Nasal... Stage IVB Nasop... Stage IVB Oroph... Stage IVC Lip a... Stage IVC Nasal... Stage IVC Nasop... Stage IVC Oroph... Head and Neck C... Oropharyngeal C... HNSCC Stage IV Lip an...	Cetuximab Ficlatuzumab	18 Years -	University of Arizona

Spots Global Cancer Trial Database for stage iva nasopharyngeal keratinizing squamous cell carcinoma