Clinical trial NCT02277197 (phase 1, status: completed)
Conditions: carcinoma, squamous cell of head and neck, squamous cell carcinoma of the head and neck, squamous cell carcinoma, head and neck
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8, C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: ficlatuzumab, cetuximab
SMILES: [H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

        Each patient must meet all of the following inclusion criteria to be enrolled in the study:

          -  Patients must have histologically confirmed HNSCC, from any primary site.
             Nasopharyngeal carcinoma, WHO Type I (keratinizing), will be included. Squamous cell
             carcinoma of unknown primary, clearly related to the head and neck, will be included.

          -  Recurrent/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.

          -  In the dose-finding phase, patients may be cetuximab-exposed or cetuximab-naïve. If
             the most recent line of therapy included cetuximab, a two-week washout period without
             cetuximab dosing is required.

          -  Patients must have previously received, not tolerated, or been judged clinically
             unsuitable for platinum-containing therapy.

          -  In the dose-expansion phase, patients must be cetuximab-resistant by fulfilling at
             least one of the criteria defined below:

               -  Disease recurrence within 6 months of completing definitive radiotherapy for
                  locally advanced disease. Radiation must have included concurrent cetuximab.
                  Induction chemotherapy, if given, may or may not have included cetuximab.

               -  Disease progression during, or within 6 months, of cetuximab treatment in the
                  recurrent/metastatic setting. Prior cetuximab exposure may have occurred in
                  first, second and/or third line.

               -  If the most recent line of therapy included cetuximab, a two-week washout period
                  without cetuximab dosing is required.

          -  Eastern Cooperative Oncology Group Performance Status 0-1 at time of informed consent
             (see Appendix B)

          -  Age ≥ 18 years

          -  Patients must consent to a research biopsy of tumor tissue at baseline, for conduct of
             correlative studies. Archived biopsy material may not be substituted.

          -  Measurable disease per RECIST criteria, version 1.1 (see section 6)

          -  Patients must have the following laboratory values measured within 28 days of
             registration:

               -  Absolute neutrophil count (ANC) ≥ 1500/mm3

               -  Platelet count (PLT) ≥ 100,000/mm3

               -  Creatinine clearance ≥ 40 ml/min as determined by 24-hour collection or 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)

               -  Serum bilirubin ≤ 1.5 times upper-limit of normal (ULN)

               -  AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 3 times ULN

          -  No prior severe infusion reaction to cetuximab or a monoclonal antibody

          -  Written informed consent must be obtained from all patients prior to beginning
             therapy. Patients should have the ability to understand and the willingness to sign a
             written informed consent document.

          -  If a woman of childbearing potential, documentation of negative pregnancy within 14
             days prior to first dose of ficlatuzumab. Sexually active women of childbearing
             potential must agree to use adequate contraceptive measures, while on study and for 30
             days after the last dose of study drug. All fertile female subjects (and their
             partners) must agree to use a highly effective method of contraception. 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:

        Patients meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          -  Nasopharyngeal primary site, if WHO Type II or III (non-keratinizing)

          -  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. Subjects with previously treated brain metastases will be
             allowed if the brain metastases have been stable without steroid treatment for at
             least 4 weeks following prior treatment (radiotherapy or surgery).

          -  Failure to recover to Grade 1 or baseline from all toxic effects of previous
             chemotherapy, radiation therapy, biologic therapy, 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 below), hypokalemia (acceptable values detailed below), and the acceptable
             hematologic values summarized above. A washout period of 2 weeks from prior cetuximab
             is required; a washout period of 3 weeks from any prior cytotoxic chemotherapy or
             investigational drug is required.

          -  Significant pulmonary disease, including pulmonary hypertension or interstitial
             pneumonitis.

          -  Decreased serum albumin < 30 g/L (< 3 g/dL)

          -  Peripheral edema ≥ Grade 2 per NCI-CTCAE version 4.0.

          -  Significant electrolyte imbalance prior to enrollment (note that patients may be
             supplemented to achieve acceptable electrolyte values):

               -  Hypomagnesemia <1.2 mg/dL or 0.5 mmol/L.

               -  Hypocalcemia < 8.0 mg/dL or 2.0 mmol/L.

               -  Hypokalemia < 3.0 mmol/L.

          -  Significant dermatological disease including, but not limited to, skin drying and
             fissuring, paronychial inflammation, infectious sequelae (eg, blepharitis, cheilitis,
             cellulitis, cyst). Exception: patients with Grade ≤ 2 cetuximab-related rash, xerosis,
             fissures or paronychial inflammation are eligible.

          -  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 Study
                  Day 1.

               -  History of serious arrhythmia (i.e., ventricular tachycardia, or ventricular
                  fibrillation).

               -  Cardiac arrhythmias requiring anti-arrhythmic medications.

          -  Significant thrombotic or embolic events within 4 weeks prior to Study Day 1.
             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 Study Day 1 and the patient is asymptomatic and stable on
             anti-coagulation therapy.

          -  Any other medical condition (eg, alcohol abuse) or psychiatric condition that, in the
             opinion of the 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 Study Day 1 (except for excised
             and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial
             bladder cancer, resected Stage I differentiated thyroid cancer, or T1a or T1b prostate
             cancer comprising < 5% of resected tissue with normal prostate specific antigen (PSA)
             since resection).

          -  Major surgery within 6 weeks prior to Study Day 1 (subjects must have completely
             recovered from any previous surgery prior to Study Day 1).

          -  Active infection requiring antibiotics or antifungals within 7 days prior to first
             dose of study drug.

          -  HIV-positive patients receiving combination anti-retroviral therapy are excluded from
             the study because of possible drug interactions with study drugs. Appropriate studies
             will be undertaken in patients receiving combination anti-retroviral therapy when
             indicated. Note: HIV testing is not required for entry into this protocol.

          -  Women must not be pregnant or breastfeeding because ficlatuzumab and/or cetuximab may
             be harmful to the fetus or the nursing infant. Pregnant women are excluded from this
             study because ficlatuzumab and/or cetuximab have the potential for teratogenic or
             abortifacient effects.