A Phase II Study of DOVitinib in REcurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands (DOVE)
- Histologically or cytologically confirmed ACC of major or minor salivary glands.
- Recurrent and/or metastatic disease deemed progressive that is not amenable to
surgery or curative radiotherapy.
- Measurable disease according to the Response Evaluation Criteria in Solid Tumors
(RECIST, version 1.1), defined as at least one lesion that can be accurately measured
in at least one dimension (longest diameter in the plane of measurement is to be
recorded) with a minimum size of:
- > 10 mm by CT scan (CT scan slice thickness no greater than 5 mm).
- > 10 mm caliper measurement by clinical exam (lesion which cannot be accurately
measured with calipers should be recorded as non-measurable).
- > 20 mm by chest X-ray Malignant lymph nodes: To be considered pathologically
enlarged and measurable, a lymph node must be >15mm in short axis when assessed
by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).
- Progressive disease, defined as one of the following occurring within 12 months of
i) at least a 10% increase in radiologically or clinically measurable disease; ii)
appearance of one or more new lesions, or iii) deterioration in clinical status.
- Less than 18 years of age.
- Life expectancy < 12 weeks.
- ECOG performance status > 2.
- Known brain metastases.
- Treatment with chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas
or mitomycin C) prior to entering the study or those who have not recovered from
adverse events due to agents administered more than 4 weeks earlier.
- Major surgery within 4 weeks prior to entering the study.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dovitinib.
- Taking medications that are potent CYP3A4 inducers or inhibitors (dovitinib is
metabolized primarily by the CYP3A4 liver enzyme, every effort should be made to
switch patients taking such agents or substances to other medications).
- History of cardiac dysfunction with an ECHO or MUGA scan outside the institutional
range of normal.
- QTc prolongation (defined as a QTc interval > 500 msec) or other significant ECG
- Poorly controlled hypertension (systolic blood pressure of ≥ 140 mmHg or diastolic
blood pressure of ≥ 90 mmHg).
- Any abnormal organ and marrow function as defined below:
- Leukocytes <3,000/microL
- Absolute neutrophil count <1,500/microL
- Platelets <100,000/microL
- Total bilirubin >1.5X institutional upper limit of normal (ULN)
- AST(SGOT) / ALT(SGPT) >2.5X institutional ULN
- Amylase/lipase outside normal institutional limits
- Serum creatinine >1.5X ULN
- Creatinine clearance <60mL/min/1.73 m2 for patients with creatinine levels above
- Required use of therapeutic doses of coumarin-derivative anticoagulants such as
warfarin, although doses of up to 2mg daily are permitted for prophylaxis of
thrombosis. Note: Low molecular weight heparin is permitted provided the patient's PT
INR is ≤ 1.5.
- Pre-existing condition (e.g., gastrointestinal tract disease), resulting in an
inability to take oral medication or a requirement for IV alimentation, prior
surgical procedures affecting absorption, or active peptic ulcer disease that impairs
their ability to swallow and retain dovitinib tablets.
- Pre-existing thyroid abnormality with an inability to maintain thyroid function in
the normal range with medication.
- Any of the following conditions:
- Serious or non-healing wound, ulcer, or bone fracture,
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 28 days of treatment,
- History of cerebrovascular accident (CVA) or transient ischemic attack (TIA)
within 12 months prior to study entry,
- History of pulmonary embolism within the past 12 months,
- History of myocardial infarction, cardiac arrhythmia, stable/unstable angina,
symptomatic congestive heart failure, or coronary/peripheral artery bypass graft
or stenting within 12 months prior to study entry,
- NYHA Class III or IV heart failure as defined by the NYHA functional
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infections, HIV-positive patients on combination antiretroviral therapy.
- Pregnant or lactating women.
- Psychiatric illness/social situations that would limit compliance with study
- Receiving any other investigational agent(s).
- Inability to understand or unable to provide written informed consent.