Trial Outcomes & Findings for Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma (NCT NCT01753713)

Last Updated: 2017-12-12

Results Overview

Number of anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM). The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6. Progression is defined using the Response Assessment in Neuro-Oncology (RANO) Criteria where CR = Total disappearance of lesions, PR = \>50% reduction in lesions and SD = \<25% reduction in lesions

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

6 months

Results posted on

2017-12-12

Participant Flow

Participant milestones

Participant milestones
Measure	Anti-angiogenic Therapy Patients Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Naive Patients Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Overall Study STARTED	14	19
Overall Study COMPLETED	14	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anti-angiogenic Therapy Naive Patients n=19 Participants Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 Participants Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Total n=33 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	13 Participants n=7 Participants	29 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	58 years n=5 Participants	51 years n=7 Participants	57 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	13 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	11 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	19 Participants n=5 Participants	14 Participants n=7 Participants	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Anti-angiogenic Therapy Naive Patients n=19 Participants Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 Participants Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Arm 1: Progression Free Survival (PFS)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From randomization to time of progression every 8 weeks (2 cycles of treatment) up to 32 weeks

Anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) patients with recurrent glioblastoma (GBM). Time to tumor progression (TTP), is defined as the time from randomization to time of progressive disease. So it is ongoing and will be assessed every 8 weeks …8, 16, 24, 32 …week. Progression is defined as \>25% increase in size of lesions or evidence of new lesions

Outcome measures

Outcome measures
Measure	Anti-angiogenic Therapy Naive Patients n=19 Participants Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 Participants Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Arm 2: Determine Median Time to Progression	1.8 Months Interval 1.3 to 2.8	1.8 Months Interval 0.7 to 1.8

SECONDARY outcome

Timeframe: Assessed until 30 days after treatment up to 32 weeks

Number of adverse events in patients in both populations (grade 1-5). Grade 1 are defined as mild events characterized as asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated. Grade 2 are moderate events with minimal, local or non invasive interventions indicated. Grade 3 are severe or medically significant events but not immediately life-threatening; hospitalization indicated. Grade 4 are life-threatening consequences with urgent intervention indicated. Grade 5 are deaths related to events

Outcome measures

Outcome measures
Measure	Anti-angiogenic Therapy Naive Patients n=19 Participants Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 Participants Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Toxicity Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1	217 Events	119 Events
Toxicity Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 2	109 Events	85 Events
Toxicity Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 3	55 Events	40 Events
Toxicity Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 4	2 Events	5 Events
Toxicity Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 5	1 Events	2 Events

SECONDARY outcome

Timeframe: Up to 30 days after treatment

Number of patients (both populations) with a complete response (CR-no measurable disease), partial response (PR \>50% reduction in measurable disease), minor response (MR \>25% reduction of measurable disease), stable disease (SD \<25% reduction) and progressive disease (PD \>25% measurable disease and new lesions).

Outcome measures

Outcome measures
Measure	Anti-angiogenic Therapy Naive Patients n=19 Participants Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 Participants Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Objective Response Rate Using Modified Revised Assessment in Neuro-Oncology (RANO) Criteria Complete Response	0 Participants	0 Participants
Objective Response Rate Using Modified Revised Assessment in Neuro-Oncology (RANO) Criteria Progressive Disease	8 Participants	8 Participants
Objective Response Rate Using Modified Revised Assessment in Neuro-Oncology (RANO) Criteria Stable Disease	3 Participants	2 Participants
Objective Response Rate Using Modified Revised Assessment in Neuro-Oncology (RANO) Criteria Unknown	6 Participants	4 Participants
Objective Response Rate Using Modified Revised Assessment in Neuro-Oncology (RANO) Criteria Partial Response	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months

The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6

Outcome measures

Outcome measures
Measure	Anti-angiogenic Therapy Naive Patients n=19 Participants Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 Participants Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Median Progression Free Survival	2.0 Months Interval 1.3 to 3.7	1.8 Months Interval 0.9 to 1.8

SECONDARY outcome

Timeframe: to death, approximately 2 years

The Kaplan-Meier method will be used. Overall survival is defined as the time from randomization to death.

Outcome measures

Outcome measures
Measure	Anti-angiogenic Therapy Naive Patients n=19 Participants Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 Participants Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Overall Survival	8.0 Months Interval 4.4 to 11.7	4.3 Months Interval 2.6 to 6.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 30 days after treatment

To assess the pharmacodynamic effect of dovitinib on potential plasma biomarkers that may include measuring concentrations of circulating, microparticles, PlGF, PDGF-AA, PDGF-AB, PDGF-BB, SDF-la, thrombospondin-l, Angl, and 11-6, IL-8 and FGF.

Outcome measures

Outcome data not reported

Adverse Events

Anti-angiogenic Therapy Naive Patients

Serious events: 10 serious events

Other events: 19 other events

Deaths: 1 deaths

Anti-angiogenic Therapy Patients

Serious events: 7 serious events

Other events: 14 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Manmeet Ahluwalia, MD

Case Comprehensive Cancer Center

Phone: 216-844-5060

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Anti-angiogenic Therapy Naive Patients n=19 participants at risk Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies	Anti-angiogenic Therapy Patients n=14 participants at risk Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. dovitinib: Given PO laboratory biomarker analysis: Correlative studies
Blood and lymphatic system disorders Anemia	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Gastrointestinal disorders Colitis	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
General disorders Death NOS	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	14.3% 2/14 • Number of events 2 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
General disorders Fever	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Infections and infestations Infections and infestations - Other, specify	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Infections and infestations Lung infection	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Infections and infestations Skin infection	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Investigations Platelet count decreased	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Investigations White blood cell decreased	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Cognitive disturbance	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Dizziness	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Dysarthria	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Dysphasia	5.3% 1/19 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Intracranial hemorrhage	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Nervous system disorders - Other, specify	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Nervous system disorders Seizure	10.5% 2/19 • Number of events 3 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Psychiatric disorders Confusion	15.8% 3/19 • Number of events 4 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Psychiatric disorders Delirium	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Renal and urinary disorders Acute kidney injury	10.5% 2/19 • Number of events 2 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	0.00% 0/14 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Vascular disorders Hypertension	0.00% 0/19 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	7.1% 1/14 • Number of events 1 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.
Vascular disorders Thromboembolic event	31.6% 6/19 • Number of events 6 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.	14.3% 2/14 • Number of events 2 • adverse events were monitored for at least 30 days following the last dose of treatment. For this study, the maximum time following a subject was 2 years.