Trial · NCT01434602

Phase I-II Everolimus and Sorafenib in Recurrent High-Grade Gliomas

NCT01434602, Phase 1, Phase 2, Completed, National Cancer Institute (NCI); results first posted 2022-02-01

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Phase I-II Everolimus and Sorafenib in Recurrent High-Grade Gliomas. Trials, record NCT01434602. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01434602

On this page

Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Phase I-II Everolimus and Sorafenib in Recurrent High-Grade Gliomas
NCT number: NCT01434602
Status: Completed
Phases: Phase 1, Phase 2
Enrollment: 86 participants, actual
Lead sponsor: National Cancer Institute (NCI)
Conditions: Brain Tumor, Glioblastoma, Anaplastic Glioma
Interventions: everolimus, sorafenib
First posted: 2011-09-15
Last updated: 2022-06-01
Results first posted: 2022-02-01
Limitations and caveats: This study specifically addressed the question of whether the experimental regimen had benefit in the 2 important categories of recurrent glioblastoma: those who were bevacizumab treatment naive and those participants who had failed prior bevacizumab. Different efficacy metrics were used so that the prior bevacizumab treatment arm passed the Stage 1 of the 2-stage design, whereas the bevacizumab naïve did not. This is an important concept for future studies in recurrent glioblastoma.

Source ClinicalTrials.gov

Registered outcomes12

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Maximum Tolerated Dose of Everolimus for Participants With Recurrent Malignant Gliomas	First 28 days of treatment only (cycle 1)	Maximum tolerated dose of everolimus for participants with recurrent malignant gliomas. MTD is defined as the dose at which fewer than one-third of participants experience a dose limiting toxicity (DLT) to one of the study drugs. A DLT is any grade 3 thrombocytopenia, grade 4 anemia, grade 4 neutropenia, or febrile neutropenia of any grade. Any non-hematologic grade 3 or grade 4 toxicity, excluding alopecia and/or hand/foot reaction. Failure to recover from toxicities (to grade 1 or less) to be eligible for re-treatment with everolimus within 14 days of the last dose of everolimus.
Primary	Maximum Tolerated Dose of Sorafenib for Participants With Recurrent Malignant Gliomas	First 28 days of treatment only (cycle 1)	Maximum tolerated dose of sorafenib for participants with recurrent malignant gliomas. MTD is defined as the dose at which fewer than one-third of participants experience a dose limiting toxicity (DLT) to one of the study drugs. A DLT is any grade 3 thrombocytopenia, grade 4 anemia, grade 4 neutropenia, or febrile neutropenia of any grade. Any non-hematologic grade 3 or grade 4 toxicity, excluding alopecia and/or hand/foot reaction. Failure to recover from toxicities (to grade 1 or less) to be eligible for re-treatment with sorafenib within 14 days of the last dose of sorafenib.
Primary	Percentage of Participants Who Survived Without Disease Progression at 6 Months After Treatment for Glioblastoma Participants With no Prior Bevacizumab Exposure	6 months	Percentage of participants who survived without disease progression at 6 months after treatment for glioblastoma participants with no prior bevacizumab exposure. Progression was measured by brain magnetic resonance imaging (MRI) tumor measurements. Progression is defined as \>25% increase in the sum of products of perpendicular diameters of enhancing lesions (over baseline if no decrease) on stable or increasing dose of corticosteroids; and/or significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation or therapy, not due to co-morbid events (radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects). Any new lesion.
Primary	Percentage of Participants Who Survived Without Disease Progression at 3 Months After Treatment for Glioblastoma Participants With Prior Bevacizumab Exposure	3 months	Percentage of participants who survived without disease progression at 3 months after treatment for glioblastoma participants with prior bevacizumab exposure. Progression was measured by brain magnetic resonance imaging (MRI) tumor measurements. Progression is defined as \>25% increase in the sum of products of perpendicular diameters of enhancing lesions (over baseline if no decrease) on stable or increasing dose of corticosteroids; and/or significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation or therapy, not due to co-morbid events (radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects). Any new lesion.
Primary	Percentage of Participants Who Survived Without Disease Progression at 6 Months After Treatment for Anaplastic Glioma (AG) Participants With no Prior Bevacizumab Exposure	6 months	Percentage of participants who survived without disease progression at 6 months after treatment for anaplastic glioma (AG) participants with no prior bevacizumab exposure. Progression was measured by brain magnetic resonance imaging (MRI) tumor measurements. Progression is defined as \>25% increase in the sum of products of perpendicular diameters of enhancing lesions (over baseline if no decrease) on stable or increasing dose of corticosteroids; and/or significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation or therapy, not due to co-morbid events (radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects). Any new lesion.
Secondary	Median Amount of Time Participants Survives Without Disease Progression for Groups A, B, and C Treated With Everolimus and Sorafenib	Up to 6 months	Median amount of time participants survives without disease progression for Groups A, B, and C treated with everolimus and sorafenib. Progression was measured by brain magnetic resonance imaging (MRI) tumor measurements. Progression is defined as \>25% increase in the sum of products of perpendicular diameters of enhancing lesions (over baseline if no decrease) on stable or increasing dose of corticosteroids; and/or significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation or therapy, not due to co-morbid events (radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects). Any new lesion.
Secondary	Objective Response for Participants With Recurrent Malignant Gliomas (Group A, Group B, and Group C) Treated With Everolimus and Sorafenib	After 1 cycle of treatment, or those who exhibit objective progression prior the end of cycle 1 (one cycle = 28 days).	Objective response for participants with recurrent malignant gliomas treated with everolimus and sorafenib was assessed by brain magnetic resonance imaging (MRI) tumor measurements. Complete Response is complete disappearance of all CE measurable and evaluable disease. Partial Response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of the two largest CE measurable lesions, sustained for at least 4 weeks. Progressive Disease \>25% increase in the sum of products of perpendicular diameters of enhancing lesions (over baseline if no decrease) on stable or increasing dose of corticosteroids, significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation or therapy, not due to co-morbid events, or any new lesion. Stable Disease does not qualify for CR, PR, or progression.
Secondary	Median Amount of Time a Participant Survives After Therapy for Participants With Recurrent Malignant Glioma (Group A, Group B, and Group C) Treated With Everolimus and Sorafenib Measured From the Time of Study Enrollment	From the time of study enrollment up to 1.5 years	Median amount of time a participant survives after therapy for participants with recurrent malignant glioma (Group A, Group B, and Group C) treated with everolimus and sorafenib measured from the time of study enrollment.
Secondary	Rate of Participants Symptom Severity	Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 1-2, cycle 4, cycle 6, cycle 8, cycle 10 and cycle 12 (each cycle is 28 days)	To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) self-reporting tool. The MDASI-BT consists of 23 symptoms rated on an 11-point scale (0 - not present, to 10 - as bad as you can imagine) to indicate the presence and severity of the symptom. We calculated the mean core symptom severity at the time of clinical evaluation.
Secondary	Rate of Participants Symptom Interference With Function	Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 1-2, cycle 4, cycle 6, cycle 8, cycle 10 and cycle 12 (each cycle is 28 days)	To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) self-reporting tool. The MDASI-BT consists of 23 symptoms rated on an 11-point scale (0 - did not interfere, to 10 - interfered completely) to indicate the symptoms that interfere with a participant's life in the last 24 hours. We calculated the mean symptom interference at the time of clinical evaluation.

1 to 10 of 12Source ClinicalTrials.gov

See all 12 registered outcomes

Outcomes12

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Maximum Tolerated Dose of Everolimus for Participants With Recurrent Malignant Gliomas	First 28 days of treatment only (cycle 1)		mg	NUMBER
PRIMARY	Maximum Tolerated Dose of Sorafenib for Participants With Recurrent Malignant Gliomas	First 28 days of treatment only (cycle 1)	The dosing schedule for the MTD is 400mg twice a day (BID) 7 days on/7 days off.	mg	NUMBER
PRIMARY	Percentage of Participants Who Survived Without Disease Progression at 6 Months After Treatment for Glioblastoma Participants With no Prior Bevacizumab Exposure	6 months		Percentage of participants	NUMBER
PRIMARY	Percentage of Participants Who Survived Without Disease Progression at 3 Months After Treatment for Glioblastoma Participants With Prior Bevacizumab Exposure	3 months		Percentage of participants	NUMBER
PRIMARY	Percentage of Participants Who Survived Without Disease Progression at 6 Months After Treatment for Anaplastic Glioma (AG) Participants With no Prior Bevacizumab Exposure	6 months		Percentage of participants	NUMBER
SECONDARY	Median Amount of Time Participants Survives Without Disease Progression for Groups A, B, and C Treated With Everolimus and Sorafenib	Up to 6 months		Months	MEDIAN
SECONDARY	Objective Response for Participants With Recurrent Malignant Gliomas (Group A, Group B, and Group C) Treated With Everolimus and Sorafenib	After 1 cycle of treatment, or those who exhibit objective progression prior the end of cycle 1 (one cycle = 28 days).		Participants	COUNT_OF_PARTICIPANTS
SECONDARY	Median Amount of Time a Participant Survives After Therapy for Participants With Recurrent Malignant Glioma (Group A, Group B, and Group C) Treated With Everolimus and Sorafenib Measured From the Time of Study Enrollment	From the time of study enrollment up to 1.5 years		Months	MEDIAN
SECONDARY	Rate of Participants Symptom Severity	Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 1-2, cycle 4, cycle 6, cycle 8, cycle 10 and cycle 12 (each cycle is 28 days)	78/86 participants were evaluable for this outcome measure. 1 participant had active progression before start of treatment, 3 participants did not have data available (no confirmed treatment dates), and 4 participants were missing questionnaires, thus were not counted. 0 analyzed = Participants were taken off therapy before reaching the timepoint.	score on a scale	MEAN
SECONDARY	Rate of Participants Symptom Interference With Function	Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 1-2, cycle 4, cycle 6, cycle 8, cycle 10 and cycle 12 (each cycle is 28 days)	78/86 participants were evaluable for this outcome measure. 1 participant had active progression before start of treatment, 3 participants did not have data available (no confirmed treatment dates), and 4 participants were missing questionnaires, thus were not counted. 0 analyzed = Participants were taken off therapy before reaching the timepoint.	score on a scale	MEAN

1 to 10 of 12Source ClinicalTrials.gov

See all 12 outcomes

Results by group79

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Maximum Tolerated Dose of Everolimus for Participants With Recurrent Malignant Gliomas	All Participants		5		mg
Maximum Tolerated Dose of Sorafenib for Participants With Recurrent Malignant Gliomas	All Participants		400		mg
Percentage of Participants Who Survived Without Disease Progression at 6 Months After Treatment for Glioblastoma Participants With no Prior Bevacizumab Exposure	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily		8.33	95% Confidence Interval 0.51 to 31.1	Percentage of participants
Percentage of Participants Who Survived Without Disease Progression at 3 Months After Treatment for Glioblastoma Participants With Prior Bevacizumab Exposure	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily		12.9	95% Confidence Interval 4.07 to 27.0	Percentage of participants
Percentage of Participants Who Survived Without Disease Progression at 6 Months After Treatment for Anaplastic Glioma (AG) Participants With no Prior Bevacizumab Exposure	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily		26.7	95% Confidence Interval 8.26 to 49.6	Percentage of participants
Median Amount of Time Participants Survives Without Disease Progression for Groups A, B, and C Treated With Everolimus and Sorafenib	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily		1.92	95% Confidence Interval .967 to 3.73	Months
Median Amount of Time Participants Survives Without Disease Progression for Groups A, B, and C Treated With Everolimus and Sorafenib	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily		1.17	95% Confidence Interval .933 to 1.90	Months
Median Amount of Time Participants Survives Without Disease Progression for Groups A, B, and C Treated With Everolimus and Sorafenib	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily		1.87	95% Confidence Interval .933 to 4.73	Months
Objective Response for Participants With Recurrent Malignant Gliomas (Group A, Group B, and Group C) Treated With Everolimus and Sorafenib	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on 7 Off + Everolimus 5mg Daily	Complete Response	0		Participants
Objective Response for Participants With Recurrent Malignant Gliomas (Group A, Group B, and Group C) Treated With Everolimus and Sorafenib	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	Complete Response	0		Participants

1 to 10 of 79Source ClinicalTrials.gov

See all 79 results by group

Participant flow30

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Phase I Dose Escalation	STARTED	Phase I Dose Level I Sorafenib 400mg Twice Daily + Everolimus 5mg Daily	6
Phase I Dose Escalation	STARTED	Phase I Dose Level -1 Sorafenib 400mg Twice Daily, 7 Days on, 7 Off + Everolimus 5mg Daily	7
Phase I Dose Escalation	STARTED	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0
Phase I Dose Escalation	STARTED	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0
Phase I Dose Escalation	STARTED	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0
Phase I Dose Escalation	COMPLETED	Phase I Dose Level I Sorafenib 400mg Twice Daily + Everolimus 5mg Daily	6
Phase I Dose Escalation	COMPLETED	Phase I Dose Level -1 Sorafenib 400mg Twice Daily, 7 Days on, 7 Off + Everolimus 5mg Daily	6
Phase I Dose Escalation	COMPLETED	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0
Phase I Dose Escalation	COMPLETED	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0
Phase I Dose Escalation	COMPLETED	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0

1 to 10 of 30Source ClinicalTrials.gov

See all 30 participant flow

Adverse events1,180

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Abdominal distension	Gastrointestinal disorders	Phase I Dose Level I Sorafenib 400mg Twice Daily + Everolimus 5mg Daily	0	6	0
other	Abdominal distension	Gastrointestinal disorders	Phase I Dose Level -1 Sorafenib 400mg Twice Daily, 7 Days on, 7 Off + Everolimus 5mg Daily	0	7	0
other	Abdominal distension	Gastrointestinal disorders	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0	12	0
other	Abdominal distension	Gastrointestinal disorders	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	2	40	2
other	Abdominal distension	Gastrointestinal disorders	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0	21	0
other	Abdominal pain	Gastrointestinal disorders	Phase I Dose Level I Sorafenib 400mg Twice Daily + Everolimus 5mg Daily	1	6	1
other	Abdominal pain	Gastrointestinal disorders	Phase I Dose Level -1 Sorafenib 400mg Twice Daily, 7 Days on, 7 Off + Everolimus 5mg Daily	0	7	0
other	Abdominal pain	Gastrointestinal disorders	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	2	12	3
other	Abdominal pain	Gastrointestinal disorders	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	0	40	0
other	Abdominal pain	Gastrointestinal disorders	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	1	21	1

1 to 10 of 1,180Source ClinicalTrials.gov

See all 1,180 adverse events

Adverse event totals15

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Phase I Dose Level I Sorafenib 400mg Twice Daily + Everolimus 5mg Daily	5	6
Total, all-cause mortality	Phase I Dose Level -1 Sorafenib 400mg Twice Daily, 7 Days on, 7 Off + Everolimus 5mg Daily	6	7
Total, all-cause mortality	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	9	12
Total, all-cause mortality	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	19	40
Total, all-cause mortality	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	11	21
Total, other adverse events	Phase I Dose Level I Sorafenib 400mg Twice Daily + Everolimus 5mg Daily	6	6
Total, other adverse events	Phase I Dose Level -1 Sorafenib 400mg Twice Daily, 7 Days on, 7 Off + Everolimus 5mg Daily	7	7
Total, other adverse events	Phase 2 Group A Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	12	12
Total, other adverse events	Phase 2 Group B Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	38	40
Total, other adverse events	Phase 2 Group C Dose Level -1 Sorafenib 400mg Twice Daily 7 Days on, 7 Off + Everolimus 5mg Daily	20	21

1 to 10 of 15Source ClinicalTrials.gov

See all 15 adverse event totals

Papers0

The papers the trial lists on ClinicalTrials.gov.

None in this release.

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons1

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison
Phase I Dose Level I Sorafenib 400mg Twice Daily + Everolimus 5mg Daily vs Phase I Dose Level -1 Sorafenib 400mg Twice Daily, 7 Days on, 7 Off + Everolimus 5mg Daily: Number of Participants With a Dose-limiting Toxicity (DLT)

Source Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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Read this trial from software.

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