Trial Outcomes & Findings for Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM) (NCT NCT01067469)

Last Updated: 2020-03-17

Results Overview

Participants with no disease progression as measured by magnetic resonance imaging (MRI) scans. Participants followed by MRI scans, as used for baseline tumor measurements, and removed from study if progression is documented after any cycle of treatment. PFS determined from date of registration in the trial and not date of randomization into chemotherapy arms (i.e. after surgery for resection of recurrent tumor).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

Documented from the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Results posted on

2020-03-17

Participant Flow

Recruitment Period: January 2010 to January 2015. All recruitment done The University of Texas MD Anderson Cancer Center.

Of the 83 participants enrolled 12 were screen failures and therefore never assigned to treatment arms.

Participant milestones

Participant milestones
Measure	Standard Dose Bevacizumab Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Overall Study STARTED	36	35
Overall Study 90 mg/m^2	0	12
Overall Study 75 mg/m^2	0	21
Overall Study COMPLETED	36	33
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Dose Bevacizumab Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Overall Study Withdrawal by Subject	0	1
Overall Study Disease Progression	0	1

Baseline Characteristics

Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Dose Bevacizumab n=36 Participants Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=35 Participants Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.	Total n=71 Participants Total of all reporting groups
Age, Continuous	56 years n=5 Participants	56 years n=7 Participants	56 years n=5 Participants
Age, Customized <=50 years	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Age, Customized >50 years	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants	35 participants n=7 Participants	71 participants n=5 Participants
Karnofsky Performance Status (KPS) 60-80	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Karnofsky Performance Status (KPS) 90-100	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
# Previous recurrence 1st	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
# Previous recurrence 2nd	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Documented from the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Outcome measures

Outcome measures
Measure	Standard Dose Bevacizumab n=36 Participants Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=33 Participants Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Progression Free Survival (PFS)	4.11 months Interval 2.96 to 5.55	4.34 months Interval 2.96 to 8.34

SECONDARY outcome

Timeframe: One year

Definition of Modified Radiographic Response Assessment Criteria for Glioblastoma (GBM) . Complete, Partial, Progressive Disease and Stable Disease. Radiographic response determined in comparison to the tumor measurements obtained at baseline (post-radiation scan will be baseline for newly diagnosed GBM and pre-treatment scans will be the baseline for recurrent GBM) for determination of response, and the smallest tumor measurement at either pre-treatment baseline or following initiation of therapy for determining progression.

Outcome measures

Outcome measures
Measure	Standard Dose Bevacizumab n=36 Participants Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=33 Participants Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Radiographic Response (RR) Complete Response	0 Participants	0 Participants
Radiographic Response (RR) Partial Response	11 Participants	3 Participants
Radiographic Response (RR) Progressive Disease	11 Participants	9 Participants
Radiographic Response (RR) Stable Disease	13 Participants	19 Participants

SECONDARY outcome

Timeframe: 6 Months

Outcome measures

Outcome measures
Measure	Standard Dose Bevacizumab n=36 Participants Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=33 Participants Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
6-month Progression-free Survival (PFS-6)	23.6 percentage of participants Interval 12.9 to 43.3	36.4 percentage of participants Interval 23.3 to 57.1

SECONDARY outcome

Timeframe: through study completion, an average of 2 years

Overall Survival(OS) is defined: Time of presentation to date of death or censored at last follow-up date

Outcome measures

Outcome measures
Measure	Standard Dose Bevacizumab n=36 Participants Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=33 Participants Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Overall Survival (OS)	8.3 Months Interval 6.42 to 11.58	9.6 Months Interval 6.26 to 16.73

SECONDARY outcome

Timeframe: Up to One year

Population: Data were not collected for the outcome for Time to Progression (TTP)

TTP is defined as the time from randomization to time of progressive disease

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: One year

Adverse Events grade 3 and 4 hematologic toxicities reported in safety profile of bevacizumab (Avastin) in combination with Lomustine in patients with recurrent glioblastoma using Common Terminology Criteria for Adverse Events (CTCAE) version 3.

Outcome measures

Outcome measures
Measure	Standard Dose Bevacizumab n=36 Participants Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=33 Participants Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Summary of Treatment Related Toxicities	0 Participants	24 Participants

Adverse Events

Standard Dose Bevacizumab

Serious events: 9 serious events

Other events: 26 other events

Deaths: 6 deaths

Low Dose Bevacizumab + Lomustine

Serious events: 9 serious events

Other events: 23 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Standard Dose Bevacizumab n=36 participants at risk Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=35 participants at risk Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Nervous system disorders CNS Ischemia	5.6% 2/36 • Number of events 2 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	0.00% 0/35 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Nervous system disorders CNS Hemorrhage	0.00% 0/36 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	2.9% 1/35 • Number of events 1 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Nervous system disorders Confusion	5.6% 2/36 • Number of events 2 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	5.7% 2/35 • Number of events 2 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Injury, poisoning and procedural complications Vessel injury - artery	2.8% 1/36 • Number of events 1 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	0.00% 0/35 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Musculoskeletal and connective tissue disorders Muscle weakness - generalized	0.00% 0/36 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	5.7% 2/35 • Number of events 2 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Nervous system disorders Headache	2.8% 1/36 • Number of events 2 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	0.00% 0/35 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Hepatobiliary disorders Cholecystitis	0.00% 0/36 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	2.9% 1/35 • Number of events 1 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Injury, poisoning and procedural complications Fracture	5.6% 2/36 • Number of events 2 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	0.00% 0/35 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Gastrointestinal disorders Perforation, GI	2.8% 1/36 • Number of events 1 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	0.00% 0/35 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Nervous system disorders Mental status change	0.00% 0/36 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	2.9% 1/35 • Number of events 1 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Investigations Thrombocytopenia	0.00% 0/36 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	2.9% 1/35 • Number of events 1 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Vascular disorders Thrombus, embolism	0.00% 0/36 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	2.9% 1/35 • Number of events 1 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).

Other adverse events

Other adverse events
Measure	Standard Dose Bevacizumab n=36 participants at risk Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.	Low Dose Bevacizumab + Lomustine n=35 participants at risk Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.
Metabolism and nutrition disorders alk phos	11.1% 4/36 • Number of events 4 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	20.0% 7/35 • Number of events 18 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Respiratory, thoracic and mediastinal disorders allergic rhinitis	5.6% 2/36 • Number of events 4 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	17.1% 6/35 • Number of events 11 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Metabolism and nutrition disorders ALT/SGPT	38.9% 14/36 • Number of events 35 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	31.4% 11/35 • Number of events 43 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Gastrointestinal disorders anorexia	16.7% 6/36 • Number of events 14 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	37.1% 13/35 • Number of events 29 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Metabolism and nutrition disorders AST/SGOT	13.9% 5/36 • Number of events 10 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	28.6% 10/35 • Number of events 31 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).
Nervous system disorders ataxia	0.00% 0/36 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).	5.7% 2/35 • Number of events 4 • Adverse event data collected every six weeks after baseline, up to one year (52 weeks).

Additional Information

Dr. John F de Groot/Chair Ad Interim, Neuro-Oncology

UT MD Anderson Cancer Center

Phone: 713- 745-3072

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place