Clinical trial NCT02538510 (phase 1/phase 2, status: active, not recruiting)
Conditions: head and neck squamous cell carcinoma, recurrent nasal cavity and paranasal sinus squamous cell carcinoma, recurrent nasopharynx carcinoma, recurrent salivary gland carcinoma, squamous cell carcinoma metastatic in the neck with occult primary, stage iii major salivary gland carcinoma, stage iii nasal cavity and paranasal sinus squamous cell carcinoma, stage iii nasopharyngeal carcinoma, stage iv nasopharyngeal carcinoma, stage iva major salivary gland carcinoma, stage iva nasal cavity and paranasal sinus squamous cell carcinoma, stage ivb major salivary gland carcinoma, stage ivb nasal cavity and paranasal sinus squamous cell carcinoma, stage ivc major salivary gland carcinoma, stage ivc nasal cavity and paranasal sinus squamous cell carcinoma
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, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: vorinostat
SMILES: ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Phase I run in: biopsy proven RMHNSCC with the following primary sites: nasopharynx,
             paranasal sinus, nasal cavity, skin/cutaneous sites; patients with unknown head and
             neck primary sites will be enrolled; patients with recurrent or metastatic squamous
             cell carcinomas of the head and neck (regardless of primary site) who are either
             unwilling to receive or have contraindications (deemed by treating physician) to
             standard systemic chemotherapy will also be eligible; patients with biopsy proven
             RMSGC be eligible as well

          -  Phase II expansion: biopsy proven RMHNSCC, of any primary site (including unknown
             primary) and RMSGC will be eligible

          -  Have evidence of disease progression by Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1 criteria within 3 months prior to study enrollment; if the patient was
             receiving a prior line of systemic therapy, he/she should have evidence of disease
             progression on that line of treatment prior to enrollment

          -  Have received any number lines of prior systemic therapy (including systemic therapy
             in the curative intent setting)

          -  Be willing and able to provide written informed consent for the trial and comply with
             the study visit requirements

          -  Have measurable disease based on RECIST 1.1

          -  Have provided tissue from an archival tissue sample or newly obtained core or
             excisional biopsy of a tumor lesion

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L

          -  Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated*
             creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 x
             institutional ULN (glomerular filtration rate [GFR] can also be used in place of
             creatinine or creatinine clearance [CrC])

               -  Creatinine clearance should be calculated per institutional standard

          -  Serum total bilirubin =< 1.5 x ULN

          -  Aspartate aminotransferase (AST) (glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
             time (PTT) is within therapeutic range of intended use of anticoagulants

          -  Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants

          -  Female subjects of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication; if
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy

          -  Patient is < 5 years free of another primary malignancy, except: a) if the other
             malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other
             primary malignancy is not considered clinically significant and is requiring no active
             intervention

          -  SECOND COURSE PHASE (RETREATMENT PERIOD FOR POST-COMPLETE RESPONSE RELAPSE ONLY)

          -  Subjects may be eligible to receive MK-3475 in the second course phase of this study
             if the study remains open and the subject meets the following conditions:

          -  Stopped initial treatment with MK-3475 after attaining an investigator-determined
             confirmed response according to RECIST1.1 response criteria

          -  Was treated for at least 24 weeks with MK-3475 before discontinuing therapy

          -  Received at least four treatments with MK-3475 beyond the date when the initial
             complete response (CR) was declared

          -  Experienced an investigator-determined confirmed cutaneous or radiographic disease
             progression after stopping their initial treatment with MK-3475

          -  Did not receive any anti-cancer treatment since the last dose of MK-3475

          -  Have a performance status of 0 or 1 on the ECOG performance scale

          -  Demonstrate adequate organ function as detailed above

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy test within 72 hours prior to receiving retreatment with study medication

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication; subjects of
             child bearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 2 year; male subjects should agree to use an adequate
             method of contraception starting with the first dose of study therapy through 120 days
             after the last dose of study therapy

          -  Does not have a history or current evidence of any condition, therapy, or laboratory
             abnormality that might interfere with the subject's participation for the full
             duration of the trial or is not in the best interest of the subject to participate, in
             the opinion of the treating investigator

        Exclusion Criteria:

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of treatment

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment

          -  Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not
             recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at
             baseline) from adverse events due to a previously administered agent

               -  Note: subjects with =< grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study

               -  Note: if subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting therapy

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment

          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents; subjects with vitiligo or
             resolved childhood asthma/atopy would be an exception to this rule; subjects that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study; subjects with hypothyroidism stable on hormone replacement or
             Sjogren's syndrome will not be excluded from the study

          -  Has evidence of interstitial lung disease or active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment

          -  Has received prior therapy with an anti-programmed cell death 1 (PD-1), PD-L1,
             anti-programmed cell death ligand 2 (PD-L2), anti-cluster of differentiation (CD)137,
             or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways); patients who have previously received MK-3475 or participated
             in an MK-3475 clinical trial will be ineligible

          -  Has received prior therapy with vorinostat or other epigenetic agent

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
             reactive) or hepatitis C (HCV) (e.g., HCV RNA [ribonucleic acid] qualitative is
             detected)

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment

          -  Requires total parenteral nutrition and is unable to swallow pills or unable to take a
             suspension through a gastrostomy tube