A Phase II Study of Dovitinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands (DOVE)

A Phase II Study of DOVitinib in REcurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands (DOVE)

This is a non-randomized, phase II, open label study of dovitinib in patients with progressive, recurrent and/or metastatic adenoid cystic carcinoma (ACC). The primary purpose of this study is to assess the anti-cancer effects of dovitinib in this population in order to evaluate whether dovitinib is worthy of further study in patients with progressive ACC.

Study Overview

• Status: Completed
• Conditions: Recurrent Adenoid Cystic Carcinoma of the Salivary Glands; Metastatic Adenoid Cystic Carcinoma of the Salivary Glands; Salivary Gland Cancers; ACC
• Intervention / Treatment: Drug: Dovitinib

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Calgary, Ontario, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Regional Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 study entry:

  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.

Exclusion Criteria:

• 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 abnormalities.
• 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 institutional normal
• 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 classification system.
• 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 requirements.
• Receiving any other investigational agent(s).
• Inability to understand or unable to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dovitinib; Dovitinib 500 mg PO OD (5 days on, 2 days off); Each cycle = 28 days	Drug: Dovitinib; Treatment continued until Disease Progression, Toxicity, or patient withdrawal; Other Names: TKI258; RTK Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate	The primary outcome measure is the clinical benefit rate, defined as an objective response (complete [CR] or partial [PR]) or stable disease [SD] of ≥6 months duration according to the RECIST version 1.1 criteria.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival		From the date the patient first receives study medication to the date of death or date of progression according to RECIST or symptomatic deterioration; estimated to be after 12 weeks of treatment
Overall Survival		From the date the patient first receives study medication to the date of death; patients will be followed up for survival for up to 2 years after disease progression
Safety and tolerability	Patients will be evaluated for toxicity. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occuring, serious and severe events of interest.	From the date the patient first receives study medication to the date the patient completes the study; patients will be followed up for survival for up to 2 years after disease progression

Collaborators and Investigators

• Sponsor: Ontario Clinical Oncology Group (OCOG)
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Sebastien Hotte, MD, Juravinski Cancer Centre; Principal Investigator: Greg Pond, PhD, Ontario Clinical Oncology Group (OCOG)

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 23, 2012
• First Submitted That Met QC Criteria: August 29, 2012
• First Posted (Estimate): September 3, 2012

Study Record Updates

• Last Update Posted (Estimate): September 17, 2015
• Last Update Submitted That Met QC Criteria: September 16, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: TKI258; Dovitinib; ACC; Recurrent Adenoid Cystic Carcinoma of the Salivary Glands; Metastatic Adenoid Cystic Carcinoma of the Salivary Glands; Salivary Gland Cancers; RTK Inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Mouth Neoplasms; Carcinoma; Recurrence; Carcinoma, Adenoid Cystic; Salivary Gland Neoplasms
• Other Study ID Numbers: OCOG-2012-DOVE