Trial Outcomes & Findings for Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme (NCT NCT00672243)
NCT ID: NCT00672243
Last Updated: 2013-08-07
Results Overview
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause. Progression based on Macdonald criteria is defined as a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
6 months
Results posted on
2013-08-07
Participant Flow
Patients were enrolled between May 2007 and March 2008 at the Preston Robert Tisch Brain Tumor Center at Duke.
Patients were excluded for any of the following: prior therapy with either an EGFR or mTOR antagonist; uncontrolled intercurrent illness including active infection, symptomatic congestive heart failure, unstable angina, grade 3 or greater hyperlipidemia or significant gastrointestinal, renal or liver disease, pregnancy or nursing
Participant milestones
| Measure |
Erlotinib + Sirolimus
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent Cytochrome P450, family 3, subfamily A (CY3PA)-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.
|
|---|---|
|
Overall Study
STARTED
|
32
|
|
Overall Study
COMPLETED
|
32
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme
Baseline characteristics by cohort
| Measure |
Erlotinib + Sirolimus
n=32 Participants
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
25 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
|
Age, Customized
|
54 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
|
Karnofsky Performance Scale (KPS)
100
|
4 participants
n=5 Participants
|
|
Karnofsky Performance Scale (KPS)
90
|
13 participants
n=5 Participants
|
|
Karnofsky Performance Scale (KPS)
85
|
1 participants
n=5 Participants
|
|
Karnofsky Performance Scale (KPS)
80
|
9 participants
n=5 Participants
|
|
Karnofsky Performance Scale (KPS)
70
|
5 participants
n=5 Participants
|
|
Received prior bevacizumab
Yes
|
9 participants
n=5 Participants
|
|
Received prior bevacizumab
No
|
23 participants
n=5 Participants
|
|
Enzyme-inducing anti-epileptic drug (EIAED) status
Not receiving EIAEDs
|
24 participants
n=5 Participants
|
|
Enzyme-inducing anti-epileptic drug (EIAED) status
Receiving EIAEDs
|
8 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Intent to treat (ITT)
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause. Progression based on Macdonald criteria is defined as a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.
Outcome measures
| Measure |
Erlotinib + Sirolimus
n=32 Participants
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.
|
|---|---|
|
6-month Progression-free Survival (PFS)
|
3.1 percentage of participants
Interval 0.2 to 13.7
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Intent to treat (ITT)
Time in weeks from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Progression based on Macdonald criteria is defined as a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.
Outcome measures
| Measure |
Erlotinib + Sirolimus
n=32 Participants
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.
|
|---|---|
|
Median Progression Free Survival (PFS)
|
6.9 weeks
Interval 3.9 to 11.0
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Intent to treat (ITT)
Time in weeks from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Outcome measures
| Measure |
Erlotinib + Sirolimus
n=32 Participants
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.
|
|---|---|
|
Median Overall Survival (OS)
|
33.8 weeks
Interval 21.9 to 53.6
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Intent to treat (ITT)
Best radiographic response per modified Macdonald criteria. Complete response: disappearance of all enhancing tumor, no new lesions, and no steroids or only maintenance doses. Partial response: ≥ 50% reduction in the products of the perpendicular diameters of all enhancing lesions, no new lesions, \& steroids must be at a stable/decreasing dose. Stable disease: does not qualify for complete or partial response or progression \& is stable clinically. Progression: ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration.
Outcome measures
| Measure |
Erlotinib + Sirolimus
n=32 Participants
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.
|
|---|---|
|
Best Radiographic Response
Complete Response
|
0 participants
|
|
Best Radiographic Response
Partial Response
|
0 participants
|
|
Best Radiographic Response
Stable Disease
|
15 participants
|
|
Best Radiographic Response
Progressive Disease
|
16 participants
|
|
Best Radiographic Response
Not evaluable
|
1 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Intent to treat (ITT)
Number of participants experiencing a ≥ grade 3, treatment-related, non-hematologic toxicity.
Outcome measures
| Measure |
Erlotinib + Sirolimus
n=32 Participants
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.
|
|---|---|
|
Number of Participants Experiencing a ≥ Grade 3, Treatment-related, Non-hematologic Toxicity.
|
15 participants
|
Adverse Events
Tarceva and Rapamycin
Serious events: 4 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tarceva and Rapamycin
n=32 participants at risk
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Colitis
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Mucositis oral
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
General disorders
Fever
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Infections and infestations
Skin infection
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Infections and infestations
Urinary tract infection
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Platelet count decreased
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Dehydration
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Peripheral motor neuropathy
|
3.1%
1/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Seizure
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
Other adverse events
| Measure |
Tarceva and Rapamycin
n=32 participants at risk
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Eye disorders
Blurred Vision
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Constipation
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Diarhhea
|
43.8%
14/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Mucositis oral
|
37.5%
12/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Nausea
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Rectal pain
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
General disorders
Fatigue
|
34.4%
11/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
General disorders
Fever
|
12.5%
4/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Alanine aminotransferase increase
|
37.5%
12/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Aspartate aminotransferase increased
|
34.4%
11/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Blood bilirubin increased
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Cholesterol high
|
56.2%
18/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Investigations-Other, specify: Low Total Protein
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Neutrophil count decreased
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Platelet count decreased
|
37.5%
12/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Weight loss
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
White blood cell decreased
|
21.9%
7/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Anorexia
|
15.6%
5/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
34.4%
11/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hypernatremia
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
34.4%
11/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
34.4%
11/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
12.5%
4/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hypokalemia
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Metabolism and nutrition disorders
Hyponatremia
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Ataxia
|
31.2%
10/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Cognitive disturbance
|
18.8%
6/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Depressed level of consciousness
|
12.5%
4/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Dysphasia
|
12.5%
4/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Headache
|
12.5%
4/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Memory impairment
|
18.8%
6/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Peripheral motor neuropathy
|
21.9%
7/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
18.8%
6/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Nervous system disorders
Tremor
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Psychiatric disorders
Anxiety
|
9.4%
3/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Psychiatric disorders
Confusion
|
21.9%
7/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Psychiatric disorders
Insomnia
|
15.6%
5/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Renal and urinary disorders
Urinary incontinence
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders-Other, specify: Sexual dysfunction
|
15.6%
5/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
18.8%
6/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
56.2%
18/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
|
Investigations
Investigations-Other, specify: BUN High
|
6.2%
2/32 • 2 years
All adverse events were entered using Common Toxicology Criteria (CTC) v. 3.0, but were converted to CTC v. 4.0 for entry into ClinicalTrials.gov
|
Additional Information
David A. Reardon, MD
The Preston Robert Tisch Brain Tumor Center at Duke
Phone: (919) 668-1409
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place