Study of Dovitinib (TKI258) in Adenoid Cystic Carcinoma

NCT01524692 | Completed Phase 2 Results DMC

• 1 other identifier: 15627
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to improve survival of patients with recurrent or metastatic Adenoid Cystic Carcinoma (ACC). This study will test the efficacy of the investigational drug, TKI258, in treating ACC.

Conditions

Adenoid Cystic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Determine the Objective Tumor Response Rate Following Treatment With TKI258

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by cross sectional imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  From enrollment up to 36months

Secondary Outcomes (5)

• Estimate the Progression-free Survival Following Treatment With TKI258.

  From enrollment up to first progression event

• The Adverse Event Profile of TKI258 in Subjects Who Have ACC.

  From enrollment up to 36months

• Quality of Life Measurements During TKI258 Treatment.

  Baseline FACT-G questionnaire and FACT-G questionnaire at time of off-treatment visit (average of 8.2 months)

• Feasibility of Measuring and Analyzing TKI258 Induced Changes in the Growth Rate of Adenoid Cystic Carcinomas.

  All patients provided pre-study scans with target lesions. The target lesions from pre-study scans were compared to the target lesions on the baseline scan at time 0. TG0 was measured from -6 months to time 0. TG1 is defined as time 0 to time 4 months.

• Expression of MYB Protein and Chromosomal Rearrangements of the MYB Locus

  Anticipated Reporting Date 2020

Study Arms (1)

Single ARM Dovitinib treatment

EXPERIMENTAL

Single ARM Dovitinib treatment

Drug: Dovitinib (TKI258)

Interventions

Dovitinib (TKI258) DRUG

500 mg orally on a 5-days on/2-days off schedule each week of a 4-week (28-day) cycle. Treatment will continue until progression as defined by RECIST, unacceptable adverse events, patient refusal to continue on study, or physician's decision to withdraw the patient.

Single ARM Dovitinib treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histology or cytology studies that confirm the diagnosis of adenoid cystic carcinoma. (Note: Subsequent central review of the pathology slides will be provided by Drs. Christopher Moskaluk or Henry Frierson, Department of Pathology at the University of Virginia Health Sciences Center).
• Patients must have recurrent and/or metastatic disease that is not amenable to potentially curative surgical resection or radiotherapy.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with spiral CT scan (or \>20 mm with conventional techniques). Pathologic lymph nodes are measured by shortest diameter as per RECIST.
• Patients must have serial imaging that allows measurement of tumor growth rates by change point analysis:
• \. The remote baseline study scan must be within six calendar months of the immediate pre-study scan.
• \. The remote baseline scan must have measurable disease ≥ 10 mm for non-pulmonary lesions or ≥ 4 mm for pulmonary metastases that show subsequent progression.
• \. Comparison of the remote baseline and subsequent studies must show progressive disease in 1-5 selected target lesions based on the following:
• Modified RECIST criteria (i.e. proportional increase of 1.2 or the appearance of new lesions) AND/OR
• Progression by change point analysis with an increase in the slope of the average tumor measurements of at least 0.22 b
• a = "remote baseline scan" refers to scan done prior to pre-study scan which is used to determine pre-treatment tumor growth rate.
• b = the estimated mean minus one standard deviation based on analysis of progressive tumors from untreated patients with ACC.
• \. Life expectancy \> 16 weeks.
• \. ECOG (WHO) performance status 0-2
• \. Age ≥ 18 years old
• \. Patients must have the following laboratory values:

You may not qualify if:

• Patients are ineligible for this study if he or she has any of the following:
• Patients with brain metastases
• Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, or skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer)
• Patients who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy and radiation) ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have received the last administration of nitrosurea or mitomycin-C ≤ 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have received targeted therapy (e.g. sunitinib, sorafenib, pazopanib) ≤ 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug or ≤ 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), if the measurable lesions are outside the radiation field. Also excluded would be those who have not recovered from toxicity radiotherapy.
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of serious uncontrolled ventricular arrhythmias
• Clinically significant resting bradycardia
• LVEF assessed by 2-D echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) \< 45%
• Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
• Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s)

Sponsors & Collaborators

• University of Virginia: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Dr. Patrick Dillon
• Organization: University of Virginia

pmd5b@virginia.edu

4349821495

Study Officials

• Patrick Dillon, MD

  University of Virginia Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: February 2, 2012
• Study Start: March 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: December 1, 2015
• Last Updated: November 9, 2018
• Results First Posted: May 7, 2018

Record last verified: 2018-10

Locations

US (1)