Trial Outcomes & Findings for Study of Dovitinib (TKI258) in Adenoid Cystic Carcinoma (NCT NCT01524692)

Last Updated: 2018-11-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

From enrollment up to 36months

Results posted on

2018-11-09

Participant Flow

Participant milestones

Participant milestones
Measure	Single ARM Dovitinib Treatment Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Overall Study STARTED	35
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Single ARM Dovitinib Treatment Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Study of Dovitinib (TKI258) in Adenoid Cystic Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single ARM Dovitinib Treatment n=35 Participants Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Age, Continuous	56 years n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
ECOG Performance Status	1 units on a scale n=5 Participants

PRIMARY outcome

Timeframe: From enrollment up to 36months

Population: 1 patient was not evaluable for response evaluation due to withdrawal prior to first interval scan.

Outcome measures

Outcome measures
Measure	Single ARM Dovitinib Treatment n=34 Participants Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Determine the Objective Tumor Response Rate Following Treatment With TKI258 Partial Response	2 Participants
Determine the Objective Tumor Response Rate Following Treatment With TKI258 Stable Disease	22 Participants
Determine the Objective Tumor Response Rate Following Treatment With TKI258 Progressive Disease	10 Participants

SECONDARY outcome

Timeframe: From enrollment up to first progression event

PFS is measured from enrollment up to first progression event (median= 8.2 months). 1 patient was not evaluable for response evaluation due to withdrawal prior to first interval scan.

Outcome measures

Outcome measures
Measure	Single ARM Dovitinib Treatment n=34 Participants Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Estimate the Progression-free Survival Following Treatment With TKI258.	8.2 Months Interval 7.3 to 11.0

SECONDARY outcome

Timeframe: From enrollment up to 36months

Adverse events were collected per CTCAE v3.

Outcome measures

Outcome measures
Measure	Single ARM Dovitinib Treatment n=35 Participants Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
The Adverse Event Profile of TKI258 in Subjects Who Have ACC.	35 Participants

SECONDARY outcome

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

Population: All participants filled out quality of life questionnaires.

Participants were asked to fill out FACT-G (Functional Assessment of Chronic Illness Therapy) quality of life questionnaires at baseline and off-treatment visit (average 8.2 months). This scale measures physical well-being, social/family well-being, emotional well-being, and functional well-being on a 5 point Likert scale. Scores range from 0 to 4 on a Likert scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). The raw score range for each subscale is 0-28 points and the total score range is 0-108. Higher values represent higher well-being in each functional subscale. The mean difference from baseline to off-study assessment are presented with range from minimum to maximum.

Outcome measures

Outcome measures
Measure	Single ARM Dovitinib Treatment n=35 Participants Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Quality of Life Measurements During TKI258 Treatment. Emotional Well-being mean Difference	-3 units on a scale Interval -12.0 to 11.0
Quality of Life Measurements During TKI258 Treatment. Functional Well-being subscale mean difference	-4 units on a scale Interval -12.0 to -1.0
Quality of Life Measurements During TKI258 Treatment. Physical Well-being subscale mean difference	-6 units on a scale Interval -18.0 to 7.0
Quality of Life Measurements During TKI258 Treatment. Social Well-being mean Difference	-1 units on a scale Interval -10.0 to 28.0
Quality of Life Measurements During TKI258 Treatment. Overall FACT-G mean difference	-13 units on a scale Interval -44.0 to 20.0

SECONDARY outcome

Timeframe: 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.

Population: All treated patients were required to submit pre-study cross sectional imaging from preceeding 6months in order to establish pre-study tumor growth rates. On-study scans were performed at time 0, 2, 4 months, 8, months, 12 months, 16 months.

Collect descriptive data about the change in tumor growth rates as measured by the change point method. Tumor growth rate is defined as the estimated slope (slope is then defined as Y1-Y0 divided by X1-X0) from tumor measurements taken prior to treatment (TG0). TG0 is compared with TG1 (tumor growth rate) as defined by the estimated slope after treatment (comparing time 0 to 4mo). Each patient's tumor growth profile is allowed one slope measured from pre-study (-6 months to time 0), and the other slope (time 0 to time 4 months). Change between those 2 slopes is reported. Slope is measured on a plot of time on the x axis and sum of longest diameters of RECIST target lesions on the y axis. The slope of the tumor growth curve (plotted as sum of longest diameters vs month since starting dovitinib) is measured at time points -6mo, 0, and 4 months. Pre-study scans (-6mo) were required of all patients and on-study scans were at times, 0, 2, 4months, 8months, 12mo, 16mo.

Outcome measures

Outcome measures
Measure	Single ARM Dovitinib Treatment n=35 Participants Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Feasibility of Measuring and Analyzing TKI258 Induced Changes in the Growth Rate of Adenoid Cystic Carcinomas. Slope of Tumor growth rate from -6mo to time 0	1.95 cm/month Standard Error 0.29
Feasibility of Measuring and Analyzing TKI258 Induced Changes in the Growth Rate of Adenoid Cystic Carcinomas. Slope of tumor growth rate from 0 to 4 months	0.63 cm/month Standard Error 0.18

SECONDARY outcome

Timeframe: Anticipated Reporting Date 2020

Assess archival tumor samples for the expression of MYB protein and chromosomal rearrangements of the MYB locus.

Outcome measures

Outcome data not reported

Adverse Events

Single ARM Dovitinib Treatment

Serious events: 22 serious events

Other events: 31 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	Single ARM Dovitinib Treatment n=35 participants at risk Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Blood and lymphatic system disorders Anemia	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Constipation	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Diarrhea	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Mucositis	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Nausea/Vomiting	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Stomach Pain	5.7% 2/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
General disorders Fatigue	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Renal and urinary disorders Urinary Tract Infection	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Hepatobiliary disorders Transaminitis	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Hepatobiliary disorders GGT Elevation	11.4% 4/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
General disorders Dehydration	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Blood and lymphatic system disorders Neutropenia	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Hepatobiliary disorders Hypertriglyceridemia	25.7% 9/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Psychiatric disorders Anxiety	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Blood and lymphatic system disorders Thromboembolic Event	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Cardiac disorders Hypertension	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
General disorders Pain	5.7% 2/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Skin and subcutaneous tissue disorders Acneiform Rash	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03

Other adverse events

Other adverse events
Measure	Single ARM Dovitinib Treatment n=35 participants at risk Single ARM Dovitinib treatment Dovitinib (TKI258): 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.
Blood and lymphatic system disorders Anemia	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Constipation	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Diarrhea	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Mucositis	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Nausea/Vomiting	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Gastrointestinal disorders Stomach Pain	5.7% 2/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
General disorders Fatigue	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Renal and urinary disorders Urinary Tract Infection	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Hepatobiliary disorders Transaminitis	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Hepatobiliary disorders GGT Elevation	11.4% 4/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
General disorders Dehydration	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Blood and lymphatic system disorders Neutropenia	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Metabolism and nutrition disorders Hypertriglyceridemia	25.7% 9/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Psychiatric disorders Anxiety	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Blood and lymphatic system disorders Thromboembolic Event	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Cardiac disorders Hypertension	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
General disorders Pain	5.7% 2/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03
Skin and subcutaneous tissue disorders Acneiform Rash	2.9% 1/35 • AE's and SAE's were collected from date of consent until off study date (which ranged from 0-20 months). Overall survival was collected from time of consent to June 2015 (40 months.) AE reporting was completed using CTCAE 4.03

Additional Information

Dr. Patrick Dillon

University of Virginia

Phone: 4349821495

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place