Ficlatuzumab with or without Cetuximab in Treating Patients with Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
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.
- 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); this includes: * 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
- 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; patients who decline radical surgery are eligible
- For patients with oropharyngeal primary site or unknown primary site only: tumoral human papillomavirus (HPV) status (p16) must be known; 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 deoxyribonucleic acid (DNA)
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at time of informed consent
- 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
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1
- Absolute neutrophil count (ANC) >= 1500/mm^3 (within 28 days of registration)
- Platelet count (PLT) >= 75,000/mm^3 (within 28 days of registration)
- Creatinine clearance >= 40 ml/min per estimated by the Cockcroft-Gault formula (within 28 days of registration)
- Total bilirubin =< 1.5 times upper-limit of normal (ULN) (within 28 days of registration)
- AST (aspartate aminotransferase) and ALT (alanine aminotransferase) =< 3 times ULN (within 28 days of registration)
- Magnesium >= 1.2 mg/dL or 0.5 mmol/L (within 28 days of registration) * Note: Patients may be supplemented to achieve acceptable electrolyte values
- Corrected calcium >= 8.0 mg/dL or 2.0 mmol/L (within 28 days of registration) * Note: Patients may be supplemented to achieve acceptable electrolyte values
- Potassium >= 3.0 mmol/L (within 28 days of registration) * Note: Patients may be supplemented to achieve acceptable electrolyte values
- Serum albumin >= 30 g/L (>= 3 g/dL) (within 28 days of registration)
- No prior severe infusion reaction to cetuximab or a monoclonal antibody
- Written informed consent must be obtained from all patients prior to beginning study screening procedures; patients should have the ability to understand and the willingness to sign a written informed consent document
- Documentation of negative pregnancy test within 14 days prior to registration for women of childbearing potential; (a negative urine pregnancy test must also be confirmed within 3 days of the first dose of ficlatuzumab)
- Sexually active women of childbearing potential (and their partners) must agree to use highly effective contraceptive measures, while on study and for 60 days after the last dose of study drug; 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)
- 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 hepatocyte growth factor (HGF)/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or ARQ197
- Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed; 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
- Cetuximab within the prior 2 weeks of start of study drug administration; a washout period of 2 weeks from prior cetuximab is required if applicable
- Cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug within the prior 3 weeks of start of study drug administration; a washout period of 3 weeks from any prior cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug is required, if applicable
- Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis
- Peripheral edema >= grade 2 per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Significant cardiovascular disease, including: * Cardiac failure New York Heart Association (NYHA) class III or IV * Myocardial infarction, 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 4 weeks 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 > 4 weeks 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
- Major surgery within 6 weeks prior to registration (subjects must have completely recovered from any previous surgery prior to registration)
- Active infection requiring systemic antibiotics or antifungals within 7 days prior to first dose of study drug; exception: tetracycline family antibiotics (tetracycline, doxycycline, minocycline) administered for the management of cetuximab-related rash may be continued per the investigator’s judgment
- Patients 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
Locations & Contacts
Contact: Panayiotis (Panos) Savvides
Contact: Julie E. Bauman
Contact: Christine H. Chung
Contact: Nabil F. Saba
Contact: Nabil F. Saba
Contact: Yanis Boumber
Trial Objectives and Outline
I. To assess the efficacy of ficlatuzumab, with or without concurrent cetuximab, in patients with cetuximab-resistant, recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) as measured by progression-free survival (PFS).
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.
Trial Phase & Type
Banner University Medical Center - Tucson
Julie E. Bauman
Secondary IDs NCI-2017-02209, AVEO, AV-299-17-117i
Clinicaltrials.gov ID NCT03422536