Trial Outcomes & Findings for BrUOG 329 Onivyde & Metronomic Temozolomide in Recurrent Glioblastoma (NCT NCT03119064)

NCT ID: NCT03119064

Last Updated: 2022-12-13

Results Overview

To evaluate the maximum tolerated dose of nanoliposomal irinotecan with continuous low-dose temozolomide for patients with recurrent glioblastoma.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Every two weeks for 4 weeks

Results posted on

2022-12-13

Participant Flow

Participant milestones

Participant milestones
Measure	Dose 1 Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 1 50mg/m2 IV every 2 weeks	Dose 2 Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks
Overall Study STARTED	9	3
Overall Study COMPLETED	9	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

BrUOG 329 Onivyde & Metronomic Temozolomide in Recurrent Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose 1 n=9 Participants Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 1 50mg/m2 IV every 2 weeks	Dose 2 n=3 Participants Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks	Total n=12 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	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	54 years n=5 Participants	64 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	2 Participants n=7 Participants	10 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	0 Participants n=7 Participants	0 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	9 participants n=5 Participants	3 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Every two weeks for 4 weeks

To evaluate the maximum tolerated dose of nanoliposomal irinotecan with continuous low-dose temozolomide for patients with recurrent glioblastoma.

Outcome measures

Outcome measures
Measure	All Participants n=12 Participants Temozolomide: until disease progression. Nanoliposomal irinotecan : IV every 2 weeks	Dose 2 Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks
Determination of Maximum Tolerated Dose (MTD)	50 mg/m^2	—

PRIMARY outcome

Timeframe: Every 2 months on study treatment then very 3 months once treatment has stopped, until progression of disease up to 2 years.

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	All Participants n=9 Participants Temozolomide: until disease progression. Nanoliposomal irinotecan : IV every 2 weeks	Dose 2 n=3 Participants Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks
Response Partial Response	1 participants	1 participants
Response Progressive Disease	8 participants	2 participants

PRIMARY outcome

Timeframe: Collected every 3 months once treatment has stopped, until progression of disease, up to 2 years.

Outcome measures

Outcome measures
Measure	All Participants n=9 Participants Temozolomide: until disease progression. Nanoliposomal irinotecan : IV every 2 weeks	Dose 2 n=3 Participants Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks
Survival Status of Participants Treated With Nanaliposomal Irinotecan With Continuous Low-dose Temozolomide in Patients With Recurrent Glioblastoma. Deceased	8 Participants	2 Participants
Survival Status of Participants Treated With Nanaliposomal Irinotecan With Continuous Low-dose Temozolomide in Patients With Recurrent Glioblastoma. Alive	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline through 30 days post off study treatment

Treatment emergent toxicities of nanoliposomal irinotecan with continuous low-dose temozolomide using CTCAE version 4.03, grades 2 through 4

Outcome measures

Outcome measures
Measure	All Participants n=9 Participants Temozolomide: until disease progression. Nanoliposomal irinotecan : IV every 2 weeks	Dose 2 n=3 Participants Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks
Toxicities Neutropenia	0 events	1 events
Toxicities ALT/AST	2 events	1 events
Toxicities Hypokalemia	1 events	1 events
Toxicities Hypophosphatemia	1 events	0 events
Toxicities Nausea	1 events	2 events
Toxicities Fatigue	2 events	2 events
Toxicities Diarrhea	0 events	2 events
Toxicities Anorexia	0 events	2 events
Toxicities Dehydration	0 events	2 events
Toxicities Urticaria	1 events	0 events

Adverse Events

Dose 1

Serious events: 4 serious events

Other events: 9 other events

Deaths: 8 deaths

Dose 2

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Dose 1 n=9 participants at risk Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 1 50mg/m2 IV every 2 weeks	Dose 2 n=3 participants at risk Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks
Respiratory, thoracic and mediastinal disorders Aspiration	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Cerebral edema	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Injury, poisoning and procedural complications Fall	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Injury, poisoning and procedural complications Fracture	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Intracranial hemorrhage	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Respiratory, thoracic and mediastinal disorders Acute pneumonia	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Infections and infestations Skin infection	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Vascular disorders Thromboembolic event	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Surgical and medical procedures Craniotomy	33.3% 3/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Muscle weakness right-sided	0.00% 0/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Infections and infestations C.diff	0.00% 0/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.

Other adverse events

Additional Information

Heinrich Elinzano, MD

Brown University Oncology Research Group

Phone: 401-863-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dose 1 n=9 participants at risk Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 1 50mg/m2 IV every 2 weeks	Dose 2 n=3 participants at risk Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks
Psychiatric disorders Agitation	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Investigations ALT increased	33.3% 3/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Psychiatric disorders Anxiety	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Investigations AST increased	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Cognitive distrubance	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders Constipation	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Respiratory, thoracic and mediastinal disorders Cough	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders Diarrhea	55.6% 5/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Dizziness	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Dysgeusia	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
General disorders Edema limbs	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Injury, poisoning and procedural complications Fall	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
General disorders Fatigue	33.3% 3/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders Fecal incontinence	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders Bloating	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders GERD	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Headache	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	33.3% 1/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders Hemorrhoidal hemorrhage	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders Hemorrhoids	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Blood and lymphatic system disorders Anemia	33.3% 3/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Vascular disorders Hypertension	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Metabolism and nutrition disorders Hypoalbuminemia	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Metabolism and nutrition disorders Hypokalemia	33.3% 3/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Metabolism and nutrition disorders Hyponatremia	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Infections and infestations Mucosal infection	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Investigations Lymphocyte count decreased	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Gastrointestinal disorders Nausea	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
General disorders Pain	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Skin and subcutaneous tissue disorders Photosensitivity	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Investigations Platelet count decreased	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Skin and subcutaneous tissue disorders Rash	11.1% 1/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Nervous system disorders Seizure	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	0.00% 0/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.
Investigations Weight loss	22.2% 2/9 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.	66.7% 2/3 • From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.