Trial Outcomes & Findings for Ph. 2 Sorafenib + Protracted Temozolomide in Recurrent GBM (NCT NCT00597493)

Last Updated: 2013-06-24

Results Overview

Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

6 months

Results posted on

2013-06-24

Participant Flow

Participant milestones

Participant milestones
Measure	Sorafenib + Temozolomide Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure
Overall Study STARTED	32
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ph. 2 Sorafenib + Protracted Temozolomide in Recurrent GBM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sorafenib + Temozolomide n=32 Participants Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure
Age Continuous	53.6 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Sorafenib + Temozolomide n=32 Participants Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure	EIAEDs-Day 28 Blood samples taken on day 28 of cycle 1 from patients currently taking EIAEDs.	Non-EIAEDs-Day 1 Blood samples taken on day 1 of cycle 1 from patients not currently taking EIAEDs.	Non-EIAEDs-Day 28 Blood samples taken on day 28 of cycle 1 from patients not currently taking EIAEDs.
6 Month Progression Free Survival (PFS)	9.4 percentage of patients Interval 2.4 to 22.3	—	—	—

SECONDARY outcome

Timeframe: 16 months

Number of participants experiencing a toxicity of at least grade 3 that was deemed possibly, probably, or definitely related to the treatment.

Outcome measures

Outcome measures
Measure	Sorafenib + Temozolomide n=32 Participants Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure	EIAEDs-Day 28 Blood samples taken on day 28 of cycle 1 from patients currently taking EIAEDs.	Non-EIAEDs-Day 1 Blood samples taken on day 1 of cycle 1 from patients not currently taking EIAEDs.	Non-EIAEDs-Day 28 Blood samples taken on day 28 of cycle 1 from patients not currently taking EIAEDs.
Safety and Toxicity of Combination	19 participants	—	—	—

SECONDARY outcome

Timeframe: 13 months

Population: 9 participants who were on EIAEDs had 24 hour sorafenib concentration versus time profiles from both day 1 and day 28 of cycle 1. 14 participants who were not on EIAEDs underwent similar assessment for day 1 but only 10 of these participants had samples available for day 28 measurements.

Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. C-max refers to maximum plasma concentration. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAED) and those who were not were analyzed separately.

Outcome measures

Outcome measures
Measure	Sorafenib + Temozolomide n=9 Participants Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure	EIAEDs-Day 28 n=9 Participants Blood samples taken on day 28 of cycle 1 from patients currently taking EIAEDs.	Non-EIAEDs-Day 1 n=14 Participants Blood samples taken on day 1 of cycle 1 from patients not currently taking EIAEDs.	Non-EIAEDs-Day 28 n=10 Participants Blood samples taken on day 28 of cycle 1 from patients not currently taking EIAEDs.
Pharmacokinetics: C-max	3397.3 ug/L Geometric Coefficient of Variation 66.8	3813.9 ug/L Geometric Coefficient of Variation 40.7	3155.1 ug/L Geometric Coefficient of Variation 41.7	8118.8 ug/L Geometric Coefficient of Variation 60.8

SECONDARY outcome

Timeframe: 13 months

Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. T-max refers to time to maximum concentration. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAED) and those who were not were analyzed separately.

Outcome measures

Outcome measures
Measure	Sorafenib + Temozolomide n=9 Participants Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure	EIAEDs-Day 28 n=9 Participants Blood samples taken on day 28 of cycle 1 from patients currently taking EIAEDs.	Non-EIAEDs-Day 1 n=14 Participants Blood samples taken on day 1 of cycle 1 from patients not currently taking EIAEDs.	Non-EIAEDs-Day 28 n=10 Participants Blood samples taken on day 28 of cycle 1 from patients not currently taking EIAEDs.
Pharmacokinetics: T-max	8.2 hours Interval 2.0 to 24.7	2.1 hours Interval 0.0 to 2.3	24.0 hours Interval 2.0 to 25.5	4.2 hours Interval 0.0 to 8.2

SECONDARY outcome

Timeframe: 13 months

Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. AUC-24 refers to area under the plasma concentration-time curve from 0 to 24 hours. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAEDs) and those who were not were analyzed separately.

Outcome measures

Outcome measures
Measure	Sorafenib + Temozolomide n=9 Participants Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure	EIAEDs-Day 28 n=9 Participants Blood samples taken on day 28 of cycle 1 from patients currently taking EIAEDs.	Non-EIAEDs-Day 1 n=14 Participants Blood samples taken on day 1 of cycle 1 from patients not currently taking EIAEDs.	Non-EIAEDs-Day 28 n=10 Participants Blood samples taken on day 28 of cycle 1 from patients not currently taking EIAEDs.
Pharmacokinetics: AUC-24	45309.7 ug*H/L Geometric Coefficient of Variation 61.8	47148.2 ug*H/L Geometric Coefficient of Variation 65.7	45238.7 ug*H/L Geometric Coefficient of Variation 44.1	128820.8 ug*H/L Geometric Coefficient of Variation 73.2

Adverse Events

Sorafenib + Temozolomide

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sorafenib + Temozolomide n=32 participants at risk Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure
Gastrointestinal disorders Pancreatitis	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Infections and infestations Lung infection	3.1% 1/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Alanine aminotransferase increased	3.1% 1/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Alkaline phosphatase increased	3.1% 1/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Aspartate aminotransferase increased	3.1% 1/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Blood bilirubin increased	3.1% 1/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Lipase increased	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Serum amylase increased	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Seizure	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Psychiatric disorders Confusion	3.1% 1/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov

Other adverse events

Other adverse events
Measure	Sorafenib + Temozolomide n=32 participants at risk Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changs in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure
Blood and lymphatic system disorders Anemia	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Eye disorders Blurred vision	15.6% 5/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Gastrointestinal disorders Constipation	21.9% 7/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Gastrointestinal disorders Diarrhea	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Gastrointestinal disorders Mucositis oral	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Gastrointestinal disorders Nausea	12.5% 4/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
General disorders Fatigue	21.9% 7/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Infections and infestations Lung infection	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Infections and infestations Sinusitis	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Alanine aminotransferase increased	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Aspartate aminotransferase increased	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Lipase increased	25.0% 8/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Neutrophil count decreased	15.6% 5/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Platelet count decreased	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations Serum amylase increased	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Investigations White blood cell decreased	28.1% 9/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Metabolism and nutrition disorders Anorexia	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Metabolism and nutrition disorders Hyperglycemia	18.8% 6/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Metabolism and nutrition disorders Hypoalbuminemia	12.5% 4/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Metabolism and nutrition disorders Hypocalcemia	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Metabolism and nutrition disorders Hypoglycemia	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Metabolism and nutrition disorders Hypokalemia	12.5% 4/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Metabolism and nutrition disorders Hypophosphatemia	15.6% 5/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Ataxia	15.6% 5/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Cognitive disturbance	18.8% 6/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Depressed level of consciousness	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Dizziness	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Dysphasia	9.4% 3/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Headache	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Memory impairment	18.8% 6/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Peripheral motor neuropathy	18.8% 6/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Peripheral sensory neuropathy	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Nervous system disorders Tremor	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Psychiatric disorders Confusion	12.5% 4/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Psychiatric disorders Depression	12.5% 4/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Psychiatric disorders Insomnia	12.5% 4/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Sexual Dysfunction	12.5% 4/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Respiratory, thoracic and mediastinal disorders Dyspnea	18.8% 6/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	21.9% 7/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Skin and subcutaneous tissue disorders Pruritus	6.2% 2/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
Skin and subcutaneous tissue disorders Rash maculo-papular	18.8% 6/32 • 16 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov

Additional Information

David Reardon, MD

Duke University Health System

Phone: 617-632-2166

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place