Axitinib (AG-013736) in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma
Condition: Adenoid Cystic Carcinoma
MeSH terms: Carcinoma; Carcinoma, Adenoid Cystic
Intervention: AG-013736 (AXITINIB)
Intervention description: All eligible patients will receive a starting axitinib dose of 5 mg twice daily (BID) taken orally in 4-week (28-day) cycles. Patients who tolerate axitinib with no adverse events related to study drug above CTCAE v. 4.0 Grade 2 for a consecutive 2-week period may have their dose increased by one dose level according to the discretion of the treating physician (NOT allowed for patients with blood pressure (BP) > 150/90 mm Hg or who are receiving antihypertensive medication). This dose escalation is not mandatory. RECIST v1.1 tumor assessments will be made at baseline (CT or MRI) and then approximately every 2 cycles (or every 8 weeks (+/- 1 week)). After 10 months, imaging will be done every 3 cycles (or every 12 weeks (+/- 1 week)). Patients may remain on study until progression of disease or unacceptable toxicity.
Intervention MeSH terms: Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: axitinib (AG-013736); recurrent; metastatic; 12-004

Summary:

      The purpose of this study is to find out what effects, good and/or bad, a new treatment
      called axitinib has on the patient and adenoid cystic carcinoma. This type of cancer study is
      called a phase II study.

      Axitinib is an oral medication that can interfere with cancer cell growth and reduce the
      growth of blood vessels around tumors. This study will help find out if axitinib is a useful
      drug for treating patients with adenoid cystic carcinomas. Axitinib is an experimental drug
      that has not yet been approved by the Food and Drug Administration for use in adenoid cystic
      carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have MSKCC pathologically confirmed adenoid cystic carcinoma. Cancers
             arising from non-salivary gland primary sites are allowed.

          -  Patients must have locally advanced and/or recurrent and/or metastatic disease not
             amenable to potentially curative surgery or radiotherapy.

          -  At least 2 weeks must have elapsed since the end of prior systemic treatment (4 weeks
             for bevacizumab- containing regimens), radiotherapy, or surgical procedure with
             resolution of all treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤1 (or
             tolerable grade 2) or back to baseline except for alopecia or hypothyroidism.

          -  Patients must have RECIST v1.1 measurable disease, defined as at least one lesion that
             can be accurately measured in at least one dimension (longest diameter to be recorded
             for non-nodal lesions and short axis for nodal lesions) as > or = to 20 mm with
             conventional techniques or as > or = to 10 mm with spiral CT scan.

          -  Patients must have documentation of a new or progressive lesion on a radiologic
             imaging study performed within 6 months prior to study enrollment (progression of
             disease over any interval is allowed) and/or new/worsening disease related symptoms.
             Note: This assessment will be performed by the treating investigator. Evidence of
             progression by RECIST criteria is not required.

          -  Patients must have archival tissue from the primary tumor or metastases available for
             correlative studies. Either a paraffin block or twenty unstained slides containing 5μm
             sections are acceptable. If twenty slides are not available, a lesser amount may be
             acceptable after discussion with the study Principal Investigator, Dr. Alan L. Ho.

          -  Male or female, age > or = to 18 years.

          -  ECOG performance status < or = to 2 (Karnofsky > or = to 60%, see Appendix A).

          -  Life expectancy of ≥ 12 weeks.

        Adequate organ function as defined by the following criteria:

          -  absolute neutrophil count (ANC) > 1000 cells/mm3

          -  platelets > or = to 75,000 cells/mm3

          -  Hemoglobin > or = to 9.0 g/dL

          -  AST and ALT < or = to 2.5 x upper limit of normal (ULN), unless there are liver
             metastases in which case AST and ALT < 5.0 x ULN

          -  Total bilirubin < or = to 1.5 x ULN

          -  Serum creatinine < or = to 1.5 x ULN or calculated creatinine clearance > or = to 60
             ml/min

          -  Urinary protein < 2+ by urine dipstick. If dipstick is > or = to 2+ then a 24-hour
             urine collection can be done and the patient may enter only if urinary protein is < 2
             g per 24 hours.

          -  Women of child-bearing potential and men must agree to use adequate contraception
             prior to study entry, for the duration of study participation, and for 6 months after
             discontinuing study treatment.

        Exclusion Criteria:

          -  Major surgery < 2 weeks or radiation therapy < 2 weeks of starting the study
             treatment.

          -  Gastrointestinal abnormalities including:

               -  inability to take oral medication;

               -  malabsorption syndromes.

          -  Current use or anticipated need for treatment with drugs that are known potent CYP3A4
             inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,
             erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir,
             nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine)

          -  Current use or anticipated need for treatment with drugs that are known CYP3A4 or
             CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole,
             phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and
             St. John's wort)

          -  Requirement for anticoagulant therapy with oral vitamin K antagonists. Low-dose
             anticoagulants for maintenance of patency of central venous access devise or
             prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular
             weight heparin is allowed.

          -  Active seizure disorder or evidence of brain metastases, spinal cord compression, or
             carcinomatous meningitis.

          -  A serious uncontrolled medical disorder or active infection that would impair their
             ability to receive study treatment.

          -  Any of the following within the 12 months prior to study drug administration:
             myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft,
             symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
             attack and 6 months for deep vein thrombosis or pulmonary embolism.

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness.

          -  Dementia or significantly altered mental status that would prohibit the understanding
             or rendering of informed consent and compliance with the requirements of this
             protocol.

          -  Female patients who are pregnant or lactating.

          -  Other severe acute or chronic medical or psychiatric condition, or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the patient inappropriate for entry into
             this study.