Trial Outcomes & Findings for Sunitinib in Treating Patients With Recurrent Malignant Gliomas (NCT NCT00499473)

NCT ID: NCT00499473

Last Updated: 2016-02-29

Results Overview

Number of patients with Progression-free Survival at 6 months for Stratum 1

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

From time to registration to up to 6 months

Results posted on

2016-02-29

Participant Flow

Participant milestones

Participant milestones
Measure	Stratum I: Non-EIAC Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib.	Stratum 2: EIAC The first six patients enrolled on stratum 2 will be dosed identical to those patients on stratum 1.The dosage of the next 6-patient cohort in stratum 2 will be adjusted to that predicted by pharmacokinetic modeling to provide the same concentrations seen in first six non-enzyme inducing patients.
Overall Study STARTED	27	4
Overall Study COMPLETED	21	4
Overall Study NOT COMPLETED	6	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sunitinib in Treating Patients With Recurrent Malignant Gliomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stratum I: Patients Not on EIAC n=27 Participants Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib.	Stratum 2: Patients on EIAC n=4 Participants The first six patients enrolled on stratum 2 will be dosed identical to those patients on stratum 1.The dosage of the next 6-patient cohort in stratum 2 will be adjusted to that predicted by pharmacokinetic modeling to provide the same concentrations seen in first six non-enzyme inducing patients.	Total n=31 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	21 Participants n=5 Participants	4 Participants n=7 Participants	25 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	4 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	4 participants n=7 Participants	31 participants n=5 Participants

PRIMARY outcome

Timeframe: From time to registration to up to 6 months

Population: Only 21 patients were evaluable for PFS

Number of patients with Progression-free Survival at 6 months for Stratum 1

Outcome measures

Outcome measures
Measure	Stratum I: Non-EIAC n=21 Participants Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib.	Stratum 2: EIAC The first six patients enrolled on stratum 2 will be dosed identical to those patients on stratum 1.The dosage of the next 6-patient cohort in stratum 2 will be adjusted to that predicted by pharmacokinetic modeling to provide the same concentrations seen in first six non-enzyme inducing patients.
Progression-free Survival at 6 Months (Stratum 1)	1 patients	—

PRIMARY outcome

Timeframe: From the time of first treatment with sunitinib until completion of treatment, assessed up to 30 days

Population: MTD in Stratum 2 not determined due to lack of efficacy in Stratum 1

Maximum tolerable dose of sunitinib in patients receiving treatment with EIAC agents using dose escalation based on the steady-state trough sunitinib + SU12662 plasma concentrations on day 14 observed in patients treated in stratum 1. Six patients will be treated in each dose cohort with up to 12 patients being treated at the maximum tolerable dose for a total of 18-24 patients with gliomas receiving EIAC.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: At baseline (day 8) and days 15, 22, and 23

Population: Not determined due to early termination of the study due to lack of efficacy

Average of pre-dose values of sunitinib + SU12662 plasma concentrations equivalent to that observed in patients not receiving EIAC based on pharmacokinetic modeling.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 12 weeks

Population: Only 21 patients were evaluable for response

Confirmatory scans should also be obtained within 4 to 6 weeks following initial documentation of objective response. Confidence intervals for the true proportion will be calculated using the exact binomial method. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: 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.

Outcome measures

Outcome measures
Measure	Stratum I: Non-EIAC n=21 Participants Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib.	Stratum 2: EIAC n=4 Participants The first six patients enrolled on stratum 2 will be dosed identical to those patients on stratum 1.The dosage of the next 6-patient cohort in stratum 2 will be adjusted to that predicted by pharmacokinetic modeling to provide the same concentrations seen in first six non-enzyme inducing patients.
Confirmed Objective Response (Complete Response[CR] or Partial Response [PR]) Complete Response Rate	0 patients	0 patients
Confirmed Objective Response (Complete Response[CR] or Partial Response [PR]) Partial Response Rate	0 patients	0 patients

SECONDARY outcome

Timeframe: At 12 months after the start of treatment

Outcome measures

Outcome measures
Measure	Stratum I: Non-EIAC n=21 Participants Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib.	Stratum 2: EIAC n=4 Participants The first six patients enrolled on stratum 2 will be dosed identical to those patients on stratum 1.The dosage of the next 6-patient cohort in stratum 2 will be adjusted to that predicted by pharmacokinetic modeling to provide the same concentrations seen in first six non-enzyme inducing patients.
Percentage of Patients Progression Free at 12 Months	0 percent of patients	0 percent of patients

SECONDARY outcome

Timeframe: up to 12 months

Outcome measures

Outcome measures
Measure	Stratum I: Non-EIAC n=27 Participants Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib.	Stratum 2: EIAC n=4 Participants The first six patients enrolled on stratum 2 will be dosed identical to those patients on stratum 1.The dosage of the next 6-patient cohort in stratum 2 will be adjusted to that predicted by pharmacokinetic modeling to provide the same concentrations seen in first six non-enzyme inducing patients.
Overall Survival	5.7 months Interval 2.9 to 29.9	12.3 months Interval 3.3 to 15.6

Adverse Events

Stratum I: Non-EIAC

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Stratum 2: EIAC

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Robert Cavaliere, MD

The Ohio State University Comprehensive Cancer Center

Phone: 614-293-4968

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Stratum I: Non-EIAC n=27 participants at risk Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib.	Stratum 2: EIAC n=4 participants at risk Patients will take one 50-mg capsule of sunitinib orally once daily for 4 consecutive weeks followed by 2 weeks of rest (drug holiday) with no sunitinib. In addition to EIAC (Enzyme-inducing anticonvulsant)
Investigations Alanine aminotransferase increased	18.5% 5/27 • Number of events 6 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Blood and lymphatic system disorders Anemia	7.4% 2/27 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Anorexia	3.7% 1/27 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Investigations Aspartate aminotransferase increased	14.8% 4/27 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Eye disorders Blurred vision	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Psychiatric disorders Confusion	11.1% 3/27 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Constipation	11.1% 3/27 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Diarrhea	33.3% 9/27 • Number of events 10 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Nervous system disorders Dizziness	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	50.0% 2/4 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Dyspepsia	25.9% 7/27 • Number of events 11 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	50.0% 2/4 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 3/27 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Fatigue	40.7% 11/27 • Number of events 14 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	50.0% 2/4 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Flatulence	3.7% 1/27 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
General disorders Gait disturbance	7.4% 2/27 • Number of events 6 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Nervous system disorders Headache	18.5% 5/27 • Number of events 5 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	75.0% 3/4 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Vascular disorders Hypertension	14.8% 4/27 • Number of events 5 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Metabolism and nutrition disorders Hypoalbuminemia	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Metabolism and nutrition disorders Hypokalemia	3.7% 1/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Psychiatric disorders Insomnia	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Infections and infestations Lung infection	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Mucositis oral	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Musculoskeletal and connective tissue disorders Muscle weakness	11.1% 3/27 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Nausea	14.8% 4/27 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Nervous system disorders Nervous system disorder	11.1% 3/27 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Investigations Neutrophil count decreased	18.5% 5/27 • Number of events 5 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Musculoskeletal and connective tissue disorders Pain in extremity	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Nervous system disorders Neuropathy	14.8% 4/27 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Blood and lymphatic system disorders Platelet count decreased	11.1% 3/27 • Number of events 5 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	50.0% 2/4 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Nervous system disorders Pyramidal tract syndrome	7.4% 2/27 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Skin and subcutaneous tissue disorders Rash	11.1% 3/27 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Nervous system disorders Seizure	3.7% 1/27 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	50.0% 2/4 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorder	0.00% 0/27 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Renal and urinary disorders Urinary retention	3.7% 1/27 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Vascular disorders Vascular disorder	0.00% 0/27 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	50.0% 2/4 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Gastrointestinal disorders Vomiting	11.1% 3/27 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	0.00% 0/4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.
Investigations White blood cell decreased	18.5% 5/27 • Number of events 7 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.	25.0% 1/4 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for Adverse event reporting.