Trial Outcomes & Findings for A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma (NCT NCT01349036)

Last Updated: 2020-03-03

Results Overview

Response to treatment was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. All participants were evaluated for progression free survival (PFS), and overall survival (OS). The six-month PFS rate was defined as the number of subjects with PFS of at least 6-month duration, with PFS measured from the first day of treatment (Cycle 1, Day 1) to the date of the first documented disease progression or date of death, whichever occurs first, over a 6-month period and evaluated using the Kaplan Meier method. The rate of OS was defined as the number of subjects that survived until study exit.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

6 months post dose

Results posted on

2020-03-03

Participant Flow

A total of 38 participants who met all inclusion and none of the exclusion criteria were enrolled and received the study drug.

Enrollment planned to include approximately 40 participants (10 in Cohort 1 and 30 in Cohort 2) recruited from approximately 6 clinic sites.

Participant milestones

Participant milestones
Measure	PLX3397 - Cohort 1 (Surgical) Participants with recurrent glioblastoma who required reoperation were treated with PLX3397 for 7 days prior to surgery.	PLX3397 - Cohort 2 (Non-surgical) Participants who received PLX3397 continuously on 28 day cycles.
Overall Study STARTED	14	24
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	14	24

Reasons for withdrawal

Reasons for withdrawal
Measure	PLX3397 - Cohort 1 (Surgical) Participants with recurrent glioblastoma who required reoperation were treated with PLX3397 for 7 days prior to surgery.	PLX3397 - Cohort 2 (Non-surgical) Participants who received PLX3397 continuously on 28 day cycles.
Overall Study Disease progression	13	22
Overall Study Other	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PLX3397 - Cohort 1 (Surgical) n=14 Participants Participants with recurrent glioblastoma who required reoperation were treated with PLX3397 for 7 days prior to surgery.	PLX3397 - Cohort 2 (Non-surgical) n=24 Participants Participants with recurrent glioblastoma who received PLX3397 continuously on 28 day cycles.	Total n=38 Participants Total of all reporting groups
Age, Continuous	56.1 years STANDARD_DEVIATION 8.6 • n=5 Participants	54.1 years STANDARD_DEVIATION 11.7 • n=7 Participants	54.8 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	17 Participants n=7 Participants	25 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	21 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	24 participants n=7 Participants	38 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months post dose

Population: Response rates were assessed in the modified intent-to-treat population.

Outcome measures

Outcome measures
Measure	Surgical Cohort 1 (N=14) n=13 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).	Non-Surgical Cohort 2 (N=24) n=22 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).
Summary of Response Rates in Participants on Treatment With PLX3397 Six-month PFS rate	1 Participants	2 Participants
Summary of Response Rates in Participants on Treatment With PLX3397 Overall survival	10 Participants	21 Participants
Summary of Response Rates in Participants on Treatment With PLX3397 Complete response rate	0 Participants	0 Participants
Summary of Response Rates in Participants on Treatment With PLX3397 Partial response rate	0 Participants	0 Participants
Summary of Response Rates in Participants on Treatment With PLX3397 Stable disease rate	3 Participants	4 Participants
Summary of Response Rates in Participants on Treatment With PLX3397 Progressive disease rate	10 Participants	18 Participants
Summary of Response Rates in Participants on Treatment With PLX3397 Not Evaluable	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Pre-dose and up to 6 post dose during cycle 1, Day 15

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters, include time to maximum concentration (Tmax) and will be calculated from the Cycle 1, Day 15 values.

Outcome measures

Outcome measures
Measure	Surgical Cohort 1 (N=14) n=11 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).	Non-Surgical Cohort 2 (N=24) n=21 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	2.09 hours Standard Deviation 1.04	1.71 hours Standard Deviation 0.90

PRIMARY outcome

Timeframe: Pre-dose and up to 6 post dose during cycle 1, Day 15

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters include maximum concentration (Cmax) and will be calculated from the Cycle 1, Day 15 values.

Outcome measures

Outcome measures
Measure	Surgical Cohort 1 (N=14) n=11 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).	Non-Surgical Cohort 2 (N=24) n=21 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	7760 ng/mL Standard Deviation 2330	8030 ng/mL Standard Deviation 2790

PRIMARY outcome

Timeframe: Pre-dose and up to 6 post dose during cycle 1, Day 15

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters include an assessment of area under the curve over 0-4 hours (AUC0-4), and will be calculated from the Cycle 1, Day 15 values.

Outcome measures

Outcome measures
Measure	Surgical Cohort 1 (N=14) n=11 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).	Non-Surgical Cohort 2 (N=24) n=21 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	24900 hr*ng/mL Standard Deviation 6700	26100 hr*ng/mL Standard Deviation 9260

PRIMARY outcome

Timeframe: Pre-dose and up to 6 post dose during cycle 1, Day 15

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters include an assessment of area under the curve over 0-6 hours (AUC0-6), and will be calculated from the Cycle 1, Day 15 values.

Outcome measures

Outcome measures
Measure	Surgical Cohort 1 (N=14) n=11 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).	Non-Surgical Cohort 2 (N=24) n=21 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	36100 hr*ng/mL Standard Deviation 10000	36900 hr*ng/mL Standard Deviation 12200

SECONDARY outcome

Timeframe: Up to 1 year post dose

Population: Safety events were assessed in the Safety Population.

Outcome measures

Outcome measures
Measure	Surgical Cohort 1 (N=14) n=14 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).	Non-Surgical Cohort 2 (N=24) n=24 Participants Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Any Event	12 Participants	22 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Fatigue	6 Participants	14 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Constipation	3 Participants	1 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Nausea	1 Participants	3 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Hair color changes	2 Participants	4 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Aspartate aminotransferase increased	3 Participants	3 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Alanine aminotransferase increased	2 Participants	3 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Decreased appetite	3 Participants	3 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Headache	1 Participants	3 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Pyrexia	2 Participants	1 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Dry Mouth	2 Participants	0 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Rash	2 Participants	1 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Neutropenia	0 Participants	3 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Lymphopenia	2 Participants	0 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Blood Lactate Dehydrogenase Increased	2 Participants	1 Participants
Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population) Hypertension	2 Participants	0 Participants

Adverse Events

PLX3397 - Cohort 1 (Surgical)

Serious events: 8 serious events

Other events: 14 other events

Deaths: 0 deaths

PLX3397 - Cohort 2 (Non-surgical)

Serious events: 11 serious events

Other events: 22 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Daiichi Sankyo Inc.

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	PLX3397 - Cohort 1 (Surgical) n=14 participants at risk Participants with recurrent glioblastoma who required reoperation were treated with PLX3397 for 7 days prior to surgery.	PLX3397 - Cohort 2 (Non-surgical) n=24 participants at risk Participants who received PLX3397 continuously on 28 day cycles.
Nervous system disorders Convulsion	21.4% 3/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	20.8% 5/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Nervous system disorders Cerebrovascular accident	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Nervous system disorders Dysarthria	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Nervous system disorders Headache	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Nervous system disorders Hydrocephalus	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Infections and infestations Pneumonia	14.3% 2/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Infections and infestations Meningitis	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Blood and lymphatic system disorders Anaemia	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Investigations ALT increased	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Investigations AST increased	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Investigations INR increased	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Investigations WBC count decreased	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Vascular disorders Hypertension	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Vascular disorders Thrombosis	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Gastrointestinal disorders Nausea	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
General disorders Oedema peripheral	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Metabolism and nutrition disorders Dehydration	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Musculoskeletal and connective tissue disorders Muscular weakness	7.1% 1/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	0.00% 0/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/14 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.	4.2% 1/24 • Adverse event data were collected from after the first dose to 28 days after the last dose. Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.