Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112736
First received: June 2, 2005
Last updated: May 29, 2015
Last verified: May 2015
Results First Received: April 28, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Diffuse Astrocytoma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Adult Pilocytic Astrocytoma
Adult Pineal Gland Astrocytoma
Adult Subependymal Giant Cell Astrocytoma
Recurrent Adult Brain Tumor
Interventions: Drug: erlotinib
Drug: temsirolimus
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Other: pharmacological study

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled between 2005 and 2008. Patients were recruited from outpatient medical clinics and referrals.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Phase I (Erlotinib & Temsirolimus)

PHASE I: Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 (dose escalation). Every 28 days until disease progression or unacceptable toxicity.

erlotinib: Given orally

temsirolimus: Given IV

pharmacological study: Correlative studies

Phase II (Erlotinib & Temsirolimus)

Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 at MTD phse I. Every 28 days until disease progression or unacceptable toxicity.

PHASE II (preoperative component): Patients who are surgical candidates may opt to undergo surgical resection of the tumor. Beginning 5-7 days before surgery, these patients receive oral erlotinib once daily until surgery. Patients also receive temsirolimus IV over 30 minutes at the MTD and then undergo surgical resection of the tumor 3-24 hours later. Beginning 2-4 weeks after surgery, patients receive temsirolimus at the MTD and erlotinib as in phase I.

therapeutic conventional surgery: Undergo surgical resection

laboratory biomarker analysis: Correlative studies


Participant Flow:   Overall Study
    Phase I (Erlotinib & Temsirolimus)     Phase II (Erlotinib & Temsirolimus)  
STARTED     22     47  
COMPLETED     21 [1]   47 [2]
NOT COMPLETED     1     0  
1 pt never had had RX due rapid decline                 1                 0  
[1] 12 of Phase I pts treated at MTD and hence considered part of the Phase II analysis
[2] 12 additional pts from phase 1 study were used in analysis for Phase 2 as they were treated at MTD



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

pts had to meet eligibility criteria and recieve at least one dose of treatment.

22 eligible pts enrolled in phase 1, but 1 pt declined before starting any treatment and was excluded from analysis - 12 pts were treated at MTD and thus included in the Phase 2 analysis, hence only 9 patients remained for analysis for phase 1


Reporting Groups
  Description
Phase I n=9

PHASE I: Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 (dose escalation). Every 28 days until disease progression or unacceptable toxicity.

erlotinib: Given orally

temsirolimus: Given IV

Phase II n=16

Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 at MTD phse I. Every 28 days until disease progression or unacceptable toxicity.

Anaplastic Glioma

erlotinib: Given orally

temsirolimus: Given IV

Phase II n=43

Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 at MTD phse I. Every 28 days until disease progression or unacceptable toxicity.

Glioblastoma

erlotinib: Given orally

temsirolimus: Given IV

Total Total of all reporting groups

Baseline Measures
    Phase I n=9     Phase II n=16     Phase II n=43     Total  
Number of Participants  
[units: participants]
  9     16     43     68  
Age  
[units: years]
Median (Full Range)
  57   (33 to 74)     47   (29 to 72)     50   (20 to 69)     51   (20 to 74)  
Gender  
[units: participants]
       
Female     4     4     12     20  
Male     5     12     31     48  
Karnofsky Performance Scale (KPS) [1]
[units: units on a scale]
Median (Full Range)
  90   (70 to 100)     90   (60 to 100)     90   (60 to 100)     90   (60 to 100)  
Prior Chemotherapy treatments  
[units: treatments]
Median (Full Range)
  2   (0 to 3)     1   (1 to 3)     1   (0 to 3)     1   (0 to 3)  
Histology  
[units: participants]
       
anaplastic glioma     3     16     0     19  
glioblastoma     6     0     43     49  
[1]

The KPS scores range from 0 (lowest score) to 100 (highest score).

The higher the score the better able to carry out daily activities

100-80: able to carry on normal activity and to work; No special care

70-50: Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed

40-10: unable to care for self, requires equivalent of institutional or hospital care; diseases may be progressing rapidly

0: dead




  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Maximum Tolerated Dose (Phase I)   [ Time Frame: based on first 4 weeks of treatment - cycle 1 ]

2.  Primary:   Safety/Dose Limiting Toxities Phase I   [ Time Frame: first 4 weeks of treatment ]

3.  Primary:   Efficacy - Response Phase 1   [ Time Frame: at least 8 weeks of treatment ]

4.  Primary:   Pharmacokinetics (Phase I)   [ Time Frame: Days 1, 2 of cycle 1, prior to dosing of both drugs, at end of temsirolimus infusion and at 1,2,4,6, and 24 hr after erlotinib administration ]

5.  Primary:   Progression-free Survival at 6 Months (Phase II)   [ Time Frame: Evaluated at baseline and every other cycle, till Month 6 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Patrick Y Wen
Organization: Adult Brain Tumor Consortium (ABTC)
e-mail: pwen@partners.org


Publications of Results:

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112736     History of Changes
Obsolete Identifiers: NCT00267878
Other Study ID Numbers: NCI-2012-02921, NCI-2012-02921, CDR0000429553, NABTC04-02, NABTC-04-02, U01CA062399
Study First Received: June 2, 2005
Results First Received: April 28, 2015
Last Updated: May 29, 2015
Health Authority: United States: Food and Drug Administration