NCT01137604

A Study in Subjects With Recurrent Malignant Glioma

Completed Phase 2 Results posted Last updated 29 September 2022

What this trial tests

Phase 2 trial testing Lenvatinib in Glioma in 151 participants. Completed in 28 October 2014.

Timeline

9 November 2010

Primary endpoint
19 March 2013

28 October 2014

Quick facts

Lead sponsor	Eisai Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	151
Start date	9 November 2010
Primary completion	19 March 2013
Estimated completion	28 October 2014
Sites	5 locations across Canada, United States

Drugs / interventions tested

• Lenvatinib (LENVATINIB) — full drug profile →
• Bevacizumab (Bevacizumab-Bvzr) — full drug profile →

Conditions studied

• Glioma — all drugs for Glioma →

Sponsor

Eisai Inc. — full company profile →

Who can join

Adults 18 to 99, any sex, with Glioma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Secondary · From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (i.e., 2.4 years)

ORR was the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) based on RANO criteria and investigator's assessment. CR was defined as the disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions, and stable or improved non-enhancing (T2/FLAIR) lesions. PR was defined as greater than or equal to 50% decrease, compared to baseline, in the sum of products of perpendicular diameters of all measureable enhancing lesions sustained for at least 4 weeks. No progression of non-meas

Group	Value	95% CI
Cohort 1 - Bevacizumab	15.8	6.0 – 31.3
Cohort 1 - Lenvatinib	21.4	10.3 – 36.8
Cohort 2 - Lenvatinib	7.7	1.6 – 20.9
Cohort 3 - Lenvatinib	0.0	0.0 – 10.9

Progression Free Survival Secondary · From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

PFS was measured as the time from randomization (Cohort 1) or the first day of treatment (Cohorts 2 and 3) until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, based on investigator's assessment.

Group	Value	95% CI
Cohort 1 - Bevacizumab	2.8	1.9 – 3.6
Cohort 1 - Lenvatinib	2.4	1.8 – 3.6
Cohort 2 - Lenvatinib	2.8	1.9 – 3.7
Cohort 3 - Lenvatinib	1.8	1.0 – 2.5

Overall Survival (OS) Secondary · From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until death due to any cause or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

OS was measured as the time from the randomization date (Cohort 1) or the first day of treatment (Cohort 2 and 3) to the date of death from any cause.

Group	Value	95% CI
Cohort 1 - Bevacizumab	6.0	4.5 – 7.7
Cohort 1 - Lenvatinib	7.5	5.6 – 11.6
Cohort 2 - Lenvatinib	12.0	8.4 – NA
Cohort 3 - Lenvatinib	4.1	3.0 – 5.9

Disease Control Rate (DCR) Secondary · From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

DCR was the percentage of the participants who had BOR of CR, PR, and stable disease (SD) with the minimum duration of SD lasting greater than or equal to 7 weeks. Only participants with measurable disease at baseline were included in evaluation of DCR, based on investigator's assessment.

Group	Value	95% CI
Cohort 1 - Bevacizumab	57.9	40.8 – 73.7
Cohort 1 - Lenvatinib	50.0	34.2 – 65.8
Cohort 2 - Lenvatinib	48.7	32.4 – 65.2
Cohort 3 - Lenvatinib	28.1	13.7 – 46.7

Clinical Benefit Rate (CBR) Secondary · From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

CBR was the percentage of the participants who had BOR of CR, PR, and SD with the minimum duration of SD lasting greater than or equal to 23 weeks. Only participants with measurable disease at baseline were included in evaluation of CBR, based on investigator's assessment.

Group	Value	95% CI
Cohort 1 - Bevacizumab	15.8	6.0 – 31.3
Cohort 1 - Lenvatinib	26.2	13.9 – 42.0
Cohort 2 - Lenvatinib	17.9	7.5 – 33.5
Cohort 3 - Lenvatinib	6.3	0.8 – 20.8

Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety Secondary · For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years)

Safety was assessed by monitoring and recording all AEs including all Common Terminology Criteria for Adverse Events (CTCAE) grades (for both increasing and decreasing severity) and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; results of physical examinations, regular measurement of vital signs, and electrocardiograms (ECGs), as detailed in the Schedule of Visits and Procedures. The relationship of AEs to treatment was based on investigator judgment. Details of AEs and SAEs are provided in the reported adverse event section.

AEs

Group	Value	95% CI
Cohort 1 - Bevacizumab	38
Cohort 1 - Lenvatinib	40
Cohort 2 - Lenvatinib	39
Cohort 3 - Lenvatinib	32

SAEs

Group	Value	95% CI
Cohort 1 - Bevacizumab	9
Cohort 1 - Lenvatinib	20
Cohort 2 - Lenvatinib	12
Cohort 3 - Lenvatinib	15

Progression Free Survival (PFS) Rate at Month 6 Primary · At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3)

PFS at Month 6 was defined as the percentage of participants who remained alive and progression-free at Month 6, based on investigator's assessment. Progression was defined using Response Assessment in Neuro-Oncology (RANO) criteria, as a greater than 25% increase in enhancing lesions despite stable or increasing steroid dose, an increase (significant) in non-enhancing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) lesions that are not attributable to other non-tumor causes, and any new lesions. PFS rate at Month 6 was estimated from Kaplan-Meier (K-M) product-limit estimate of PFS

Group	Value	95% CI
Cohort 1 - Bevacizumab	11.0	3.5 – 23.4
Cohort 1 - Lenvatinib	21.2	10.4 – 34.5
Cohort 2 - Lenvatinib	8.0	1.6 – 21.6
Cohort 3 - Lenvatinib	7.6	1.3 – 21.5

Adverse events — posted to ClinicalTrials.gov

Time frame: For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 - Bevacizumab

Serious: 10/38 (26%)

Deaths: 36/38

Cohort 1 - Lenvatinib

Serious: 22/42 (52%)

Deaths: 38/42

Cohort 2 - Lenvatinib

Serious: 12/39 (31%)

Deaths: 27/39

Cohort 3 - Lenvatinib

Serious: 15/32 (47%)

Deaths: 30/32

Serious adverse events (59 terms)

Reaction	System	Cohort 1 - Bevacizumab	Cohort 1 - Lenvatinib	Cohort 2 - Lenvatinib	Cohort 3 - Lenvatinib
Convulsion	Nervous system disorders	—	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
General physical health deterioration	General disorders	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Wound dehiscence	Injury, poisoning and procedural complications	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Intestinal perforation	Gastrointestinal disorders	—	—	—	—
Large intestine perforation	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—	—
Asthenia	General disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—
Hepatitis acute	Hepatobiliary disorders	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Diverticulitis	Infections and infestations	—	—	—	—
Perirectal abscess	Infections and infestations	—	—	—	—
Skin infection	Infections and infestations	—	—	—	—

Other adverse events (117 terms — click to expand)

Reaction	System	Cohort 1 - Bevacizumab	Cohort 1 - Lenvatinib	Cohort 2 - Lenvatinib	Cohort 3 - Lenvatinib
Fatigue	General disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Dysphonia	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—
Aphasia	Nervous system disorders	—	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Confusional state	Psychiatric disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Ataxia	Nervous system disorders	—	—	—	—
Hypoaesthesia	Nervous system disorders	—	—	—	—
Agitation	Psychiatric disorders	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—
Gait disturbance	General disorders	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Memory impairment	Nervous system disorders	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—

Most-reported serious reactions: Convulsion, Hypothyroidism, Vomiting, Fatigue, General physical health deterioration, Pneumonia, Wound dehiscence, Cerebrovascular accident.

Data from ClinicalTrials.gov NCT01137604 adverse events section.

Sponsor's own description

An open-label phase 2, multicenter study in participants with recurrent malignant glioma.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Lenvatinib promotes antitumor immunity by enhancing the tumor infiltration and activation of NK cells.
   Zhang Q, Liu H, Wang H, Lu M, et al · · 2019 · cited 40× · PMID 31392076
2. Translational gap in ongoing clinical trials for glioma.
   Guishard AF, Yakisich JS, Azad N, Iyer AKV. · · 2018 · cited 17× · PMID 29066236 · DOI 10.1016/j.jocn.2017.10.001
3. Investigational new drugs for brain cancer.
   Staedtke V, Bai RY, Laterra J. · · 2016 · cited 17× · PMID 27170161 · DOI 10.1080/13543784.2016.1182497