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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Ontario Clinical Oncology Group (OCOG)
ClinicalTrials.gov Identifier:
NCT01678105
First received: August 23, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Adenoid Cystic Carcinoma of the Salivary Glands
Metastatic Adenoid Cystic Carcinoma of the Salivary Glands
Salivary Gland Cancers
ACC
Drug: Dovitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of DOVitinib in REcurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands (DOVE)

Resource links provided by NLM:


Further study details as provided by Ontario Clinical Oncology Group (OCOG):

Primary Outcome Measures:
  • Clinical Benefit Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 20
Study Start Date: November 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678105

Locations
Canada, Ontario
Tom Baker Cancer Centre
Calgary, Ontario, Canada, T2N 4N2
Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, Canada, K1H 8L6
Sponsors and Collaborators
Ontario Clinical Oncology Group (OCOG)
Novartis Pharmaceuticals
Investigators
Principal Investigator: Sebastien Hotte, MD Juravinski Cancer Centre
Study Director: Mark Levine, MD Ontario Clinical Oncology Group (OCOG)
Principal Investigator: Greg Pond, PhD Ontario Clinical Oncology Group (OCOG)
  More Information

No publications provided

Responsible Party: Ontario Clinical Oncology Group (OCOG)
ClinicalTrials.gov Identifier: NCT01678105     History of Changes
Other Study ID Numbers: OCOG-2012-DOVE
Study First Received: August 23, 2012
Last Updated: April 14, 2014
Health Authority: Canada: Health Canada

Keywords provided by Ontario Clinical Oncology Group (OCOG):
Recurrent Adenoid Cystic Carcinoma of the Salivary Glands
Metastatic Adenoid Cystic Carcinoma of the Salivary Glands
Salivary Gland Cancers
ACC
Dovitinib
TKI258
RTK Inhibitor

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Adenoid Cystic
Salivary Gland Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases

ClinicalTrials.gov processed this record on August 26, 2014