Trial Outcomes & Findings for Oral Pazopanib Plus Oral Topotecan Metronomic Antiangiogenic Therapy for Recurrent Glioblastoma Multiforme (A) Without Prior Bevacizumab Exposure and (B) After Failing Prior Bevacizumab (NCT NCT01931098)

NCT ID: NCT01931098

Last Updated: 2025-08-11

Results Overview

PFS was evaluated using the Kaplan-Meier product-limit survival curve methodology. For participants with no prior bevacizumab exposure, PFS is defined as 2 or more participants who are progression free at 6 months. For participants with prior bevacizumab exposure, PFS is defined as 1 or more participants who are progression free at 3 months. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) or clear worsening of evaluable disease or the appearance of any new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

six months from patient registration for bevacizumab naive patients, and 3 months from patient registration for patients with prior bevacizumab treatment

Results posted on

2025-08-11

Participant Flow

Participant milestones

Participant milestones
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Overall Study STARTED	9	26
Overall Study COMPLETED	9	22
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Overall Study Withdrawal by Subject	0	1
Overall Study Enrolled in different protocol	0	1
Overall Study Unable to begin trmt:active infection	0	1
Overall Study Refused further treatment	0	1

Baseline Characteristics

Oral Pazopanib Plus Oral Topotecan Metronomic Antiangiogenic Therapy for Recurrent Glioblastoma Multiforme (A) Without Prior Bevacizumab Exposure and (B) After Failing Prior Bevacizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure n=9 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure n=26 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Total n=35 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	22 Participants n=7 Participants	29 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	54.6 years STANDARD_DEVIATION 9.51 • n=5 Participants	50.81 years STANDARD_DEVIATION 13.26 • n=7 Participants	51.79 years STANDARD_DEVIATION 12.38 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	15 Participants n=7 Participants	19 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	9 Participants n=5 Participants	26 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	26 Participants n=7 Participants	34 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	26 participants n=7 Participants	35 participants n=5 Participants

PRIMARY outcome

Timeframe: six months from patient registration for bevacizumab naive patients, and 3 months from patient registration for patients with prior bevacizumab treatment

Outcome measures

Outcome measures
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure n=9 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure n=26 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Proportion of Patients That Have Progressive Survival (PFS) at Six Months From Patient Registration for Bevacizumab Naive Patients and PFS at 3 Months for Patients With Prior Bevacizumab Treatment 3 months	0.44 proportion of participants Interval 0.14 to 0.72	0.18 proportion of participants Interval 0.06 to 0.36
Proportion of Patients That Have Progressive Survival (PFS) at Six Months From Patient Registration for Bevacizumab Naive Patients and PFS at 3 Months for Patients With Prior Bevacizumab Treatment 6 months	0.11 proportion of participants Interval 0.01 to 0.39	0 proportion of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From date of registration to date of death due to any cause, up to 5 years.

OS was evaluated using the Kaplan-Meier product-limit survival curve methodology and is defined as the time from date of registration to date of death due to any cause.

Outcome measures

Outcome measures
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure n=9 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure n=26 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Overall Survival	7.1 Months Interval 2.9 to 8.2	6.3 Months Interval 2.8 to 9.1

SECONDARY outcome

Timeframe: Baseline, and Cycles 1-6

Population: One participant in the second Arm/Group did not have a best response recorded and was excluded from questions involving responders and non-responders.

Responders and Non-Responders symptom presence and severity were assessed by the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) questionnaire using an scale of (0-10); 0 being not present and 10 being the worst, and Responders were defined as patients with stable disease (SD) and partial response (PR) as their best response, and Non-responders were defined as patients with disease progression (PD) as their best response. Partial response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesion. Progressive disease is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease). And stable disease does not qualify for complete response, partial response or progression.

Outcome measures

Outcome measures
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure n=9 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure n=25 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 2	1.4 scores on a scale Standard Deviation 1.2	3.5 scores on a scale Standard Deviation 2.5
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - baseline	1.3 scores on a scale Standard Deviation 0.5	2.4 scores on a scale Standard Deviation 1.7
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Responders - baseline	1.1 scores on a scale Standard Deviation 0.4	1.9 scores on a scale Standard Deviation 1.3
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 1	—	2.3 scores on a scale Standard Deviation 1.4
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 2	0.8 scores on a scale Standard Deviation 0.4	3.5 scores on a scale Standard Deviation 2.5
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 3	—	2.9 scores on a scale Standard Deviation 3.4
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 4	2.0 scores on a scale Standard Deviation 1.7	—
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 5	—	1.5 scores on a scale
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 6	2.1 scores on a scale Standard Deviation 2.0	—
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Non-Responders - baseline	1.6 scores on a scale Standard Deviation 0.7	2.8 scores on a scale Standard Deviation 2.1
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Non-Responders - Cycle 1	—	3.0 scores on a scale Standard Deviation 1.9
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Non-Responders - Cycle 2	3.0 scores on a scale	—
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 1	—	2.5 scores on a scale Standard Deviation 1.5
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 3	—	2.9 scores on a scale Standard Deviation 3.4
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 4	2.0 scores on a scale Standard Deviation 1.7	1.5 scores on a scale
Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 6	2.1 scores on a scale Standard Deviation 2.0	—

SECONDARY outcome

Timeframe: Baseline, and Cycles 1-6

Population: One participant in the second Arm/Group did not have a best response recorded and was excluded from questions involving responders and non-responders.

Responders and Non-Responders symptom interference was assessed by the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) questionnaire that determined how much general activity, mood, work inside and outside the home, relations with other people, walking and enjoying life interfered with a participant's life rated on an scale (0-10); 0 being not present and 10 being the worst. Responders were defined as patients with stable disease (SD) and partial response (PR) as their best response, and Non-responders were defined as patients with disease progression (PD) as their best response. Partial response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesion. Progressive disease is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease). And stable disease does not qualify for complete response, partial response or progression.

Outcome measures

Outcome measures
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure n=9 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure n=25 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Responders - baseline	2.1 scores on a scale Standard Deviation 1.2	3.6 scores on a scale Standard Deviation 2.9
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 1	—	3.7 scores on a scale Standard Deviation 2.5
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 2	1.4 scores on a scale Standard Deviation 0.4	6.0 scores on a scale Standard Deviation 3.2
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 3	—	4.2 scores on a scale Standard Deviation 4.0
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 4	3.2 scores on a scale Standard Deviation 2.0	—
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 5	—	0.2 scores on a scale
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Responders - Cycle 6	2.7 scores on a scale Standard Deviation 0.9	—
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Non-Responders - baseline	1.7 scores on a scale Standard Deviation 1.2	3.9 scores on a scale Standard Deviation 3.2
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Non-Responders - Cycle 1	—	4.8 scores on a scale Standard Deviation 3.8
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Non-Responders - Cycle 2	3.0 scores on a scale	—
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - baseline	2.0 scores on a scale Standard Deviation 1.2	3.8 scores on a scale Standard Deviation 2.9
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 1	—	4.0 scores on a scale Standard Deviation 2.9
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 2	1.8 scores on a scale Standard Deviation 0.9	6.0 scores on a scale Standard Deviation 3.2
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 3	—	4.2 scores on a scale Standard Deviation 4.0
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 4	3.2 scores on a scale Standard Deviation 2.0	—
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 5	—	0.2 scores on a scale
Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle Overall Responders and Non-Responders - Cycle 6	2.7 scores on a scale Standard Deviation 0.9	—

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure n=9 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure n=26 Participants Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	9 Participants	21 Participants

Adverse Events

Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure

Serious events: 2 serious events

Other events: 9 other events

Deaths: 9 deaths

Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure

Serious events: 7 serious events

Other events: 21 other events

Deaths: 20 deaths

Serious adverse events

Serious adverse events
Measure	Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure n=9 participants at risk Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.	Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure n=26 participants at risk Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
Investigations Alanine aminotransferase increased	0.00% 0/9 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Hepatobiliary disorders Cholecystitis	0.00% 0/9 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/9 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Nervous system disorders Headache	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Infections and infestations Meningitis	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	22.2% 2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Glioblastoma	0.00% 0/9 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Nervous system disorders Seizure	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Vascular disorders Thromboembolic event	0.00% 0/9 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/9 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/9 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.

Other adverse events

Additional Information

Dr. Kevin Camphausen

National Cancer Institute

Phone: 240-760-6205

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place