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Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme

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ClinicalTrials.gov Identifier: NCT00672243
Recruitment Status : Completed
First Posted : May 6, 2008
Results First Posted : April 4, 2013
Last Update Posted : August 7, 2013
Sponsor:
Collaborators:
Genentech, Inc.
OSI Pharmaceuticals
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Glioblastoma
Gliosarcoma
Intervention Drug: Erlotinib + sirolimus
Enrollment 32
Recruitment Details Patients were enrolled between May 2007 and March 2008 at the Preston Robert Tisch Brain Tumor Center at Duke.
Pre-assignment Details 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
Arm/Group Title Erlotinib + Sirolimus
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 32
Completed 32
Not Completed 0
Arm/Group Title Erlotinib + Sirolimus
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
<=18 years
0
   0.0%
Between 18 and 65 years
25
  78.1%
>=65 years
7
  21.9%
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 32 participants
54
(40 to 71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
7
  21.9%
Male
25
  78.1%
Karnofsky Performance Scale (KPS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants
100 4
90 13
85 1
80 9
70 5
[1]
Measure Description: Karnofsky Performance Scores (KPS) range from 0-100 (100=Normal, no complaints; no evidence of disease; 90=Able to carry on normal activity; minor signs or symptoms of disease; 80=Normal activity with efforts; some signs or symptoms of disease; 70=Cares for self; unable to carry on normal activity or to do active work. Scores between intervals are possible.
Received prior bevacizumab  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants
Yes 9
No 23
Enzyme-inducing anti-epileptic drug (EIAED) status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants
Not receiving EIAEDs 24
Receiving EIAEDs 8
1.Primary Outcome
Title 6-month Progression-free Survival (PFS)
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT)
Arm/Group Title Erlotinib + Sirolimus
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.1
(0.2 to 13.7)
2.Secondary Outcome
Title Median Progression Free Survival (PFS)
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT)
Arm/Group Title Erlotinib + Sirolimus
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 32
Median (95% Confidence Interval)
Unit of Measure: weeks
6.9
(3.9 to 11)
3.Secondary Outcome
Title Median Overall Survival (OS)
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT)
Arm/Group Title Erlotinib + Sirolimus
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 32
Median (95% Confidence Interval)
Unit of Measure: weeks
33.8
(21.9 to 53.6)
4.Secondary Outcome
Title Best Radiographic Response
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT)
Arm/Group Title Erlotinib + Sirolimus
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 32
Measure Type: Number
Unit of Measure: participants
Complete Response 0
Partial Response 0
Stable Disease 15
Progressive Disease 16
Not evaluable 1
5.Secondary Outcome
Title Number of Participants Experiencing a ≥ Grade 3, Treatment-related, Non-hematologic Toxicity.
Hide Description Number of participants experiencing a ≥ grade 3, treatment-related, non-hematologic toxicity.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT)
Arm/Group Title Tarceva and Rapamycin
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 32
Measure Type: Number
Unit of Measure: participants
15
Time Frame 2 years
Adverse Event Reporting Description 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
 
Arm/Group Title Tarceva and Rapamycin
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
Tarceva and Rapamycin
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tarceva and Rapamycin
Affected / at Risk (%)
Total   4/32 (12.50%) 
Gastrointestinal disorders   
Abdominal pain  1  1/32 (3.13%) 
Colitis  1  1/32 (3.13%) 
Mucositis oral  1  1/32 (3.13%) 
General disorders   
Fever  1  2/32 (6.25%) 
Infections and infestations   
Skin infection  1  1/32 (3.13%) 
Urinary tract infection  1  1/32 (3.13%) 
Investigations   
Platelet count decreased  1  1/32 (3.13%) 
Metabolism and nutrition disorders   
Dehydration  1  1/32 (3.13%) 
Nervous system disorders   
Peripheral motor neuropathy  1  1/32 (3.13%) 
Seizure  1  2/32 (6.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTC v. 3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tarceva and Rapamycin
Affected / at Risk (%)
Total   26/32 (81.25%) 
Blood and lymphatic system disorders   
Anemia  1  3/32 (9.38%) 
Eye disorders   
Blurred Vision  1  2/32 (6.25%) 
Gastrointestinal disorders   
Constipation  1  2/32 (6.25%) 
Diarhhea  1  14/32 (43.75%) 
Mucositis oral  1  12/32 (37.50%) 
Nausea  1  3/32 (9.38%) 
Rectal pain  1  2/32 (6.25%) 
Vomiting  1  2/32 (6.25%) 
General disorders   
Fatigue  1  11/32 (34.38%) 
Fever  1  4/32 (12.50%) 
Investigations   
Alanine aminotransferase increase  1  12/32 (37.50%) 
Aspartate aminotransferase increased  1  11/32 (34.38%) 
Blood bilirubin increased  1  3/32 (9.38%) 
Cholesterol high  1  18/32 (56.25%) 
Investigations-Other, specify: Low Total Protein  1  2/32 (6.25%) 
Neutrophil count decreased  1  3/32 (9.38%) 
Platelet count decreased  1  12/32 (37.50%) 
Weight loss  1  3/32 (9.38%) 
White blood cell decreased  1  7/32 (21.88%) 
Investigations-Other, specify: BUN High  1  2/32 (6.25%) 
Metabolism and nutrition disorders   
Anorexia  1  5/32 (15.63%) 
Hyperglycemia  1  11/32 (34.38%) 
Hypermagnesemia  1  2/32 (6.25%) 
Hypernatremia  1  2/32 (6.25%) 
Hypertriglyceridemia  1  11/32 (34.38%) 
Hypoalbuminemia  1  11/32 (34.38%) 
Hypocalcemia  1  4/32 (12.50%) 
Hypokalemia  1  3/32 (9.38%) 
Hyponatremia  1  3/32 (9.38%) 
Musculoskeletal and connective tissue disorders   
Muscle weakness lower limb  1  2/32 (6.25%) 
Nervous system disorders   
Ataxia  1  10/32 (31.25%) 
Cognitive disturbance  1  6/32 (18.75%) 
Depressed level of consciousness  1  4/32 (12.50%) 
Dysphasia  1  4/32 (12.50%) 
Headache  1  4/32 (12.50%) 
Memory impairment  1  6/32 (18.75%) 
Peripheral motor neuropathy  1  7/32 (21.88%) 
Peripheral sensory neuropathy  1  6/32 (18.75%) 
Tremor  1  2/32 (6.25%) 
Psychiatric disorders   
Anxiety  1  3/32 (9.38%) 
Confusion  1  7/32 (21.88%) 
Insomnia  1  5/32 (15.63%) 
Renal and urinary disorders   
Urinary incontinence  1  2/32 (6.25%) 
Reproductive system and breast disorders   
Reproductive system and breast disorders-Other, specify: Sexual dysfunction  1  5/32 (15.63%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/32 (6.25%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  2/32 (6.25%) 
Rash acneiform  1  6/32 (18.75%) 
Rash maculo-papular  1  18/32 (56.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTC v. 3.0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: David A. Reardon, MD
Organization: The Preston Robert Tisch Brain Tumor Center at Duke
Phone: (919) 668-1409
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00672243     History of Changes
Other Study ID Numbers: Pro00000345
First Submitted: January 29, 2008
First Posted: May 6, 2008
Results First Submitted: March 30, 2011
Results First Posted: April 4, 2013
Last Update Posted: August 7, 2013