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Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

Primary Purpose

Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sorafenib tosylate
erlotinib hydrochloride
tipifarnib
temsirolimus
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Giant Cell Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma Evidence of tumor progression by MRI or CT scan within the past 14 days AND on a steroid dose that has been stable for ≥ 5 days Patients who underwent prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by either positron emission tomography or thallium scanning, magnetic resonance (MR) spectroscopy, or surgical documentation of disease Recent resection of recurrent or progressive tumor allowed Residual disease is not required Treatment for any number of prior relapses, defined as disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial treatment), allowed (phase I) No more than 3 prior therapies (initial therapy and therapy for 2 relapses) (phase II) Each of the following is considered 1 relapse: Disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial therapy) Underwent a surgical resection for relapsed disease and received no anticancer therapy for up to 12 weeks after surgical resection AND then underwent a subsequent surgical resection Received prior therapy for a low-grade glioma, followed by a surgical diagnosis of glioblastoma Failed prior radiotherapy 15 unstained paraffin slides or 1 tissue block must be available from original surgery, definitive surgery, or surgery closest to the initiation of this study (phase II) Karnofsky performance status 60-100% White Blood Cell (WBC) ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL (transfusion allowed) Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) Total bilirubin normal Creatinine < 1.5 mg/dL Prothrombin time (PT)/ international normalized ratio (INR) ≤ 1.5 (INR < 3.0 for patients on anticoagulation therapy) INR < 1.1 times upper limit of normal (ULN) (for patients on prophylactic anticoagulation therapy [low-dose warfarin]) Fasting cholesterol < 350 mg/dL (for patients receiving temsirolimus and sorafenib) Fasting triglycerides < 400 mg/dL (for patients receiving temsirolimus and sorafenib) Well-controlled hypertension (e.g., systolic blood pressure ≤ 140 mm Hg or diastolic pressure ≤ 90 mm Hg) allowed Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for at least 2 weeks (women) or 3 months (men) after completion of study treatment No peripheral neuropathy > grade 1 (for patients receiving sorafenib and tipifarnib) No evidence of bleeding diathesis or coagulopathy No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for ≥ 3 years No significant traumatic injury within the past 21 days No active infection or serious medical illness that would preclude study treatment No condition that would impair ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation or active peptic ulcer disease) No HIV disease No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole or econazole) or a history of allergic reactions attributed to any compound of similar chemical or biological composition to tipifarnib (for patients receiving sorafenib and tipifarnib) No other disease that would obscure toxicity or dangerously alter drug metabolism Recovered from prior therapy At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) (radiosensitizer does not count) At least 14 days since prior vincristine At least 21 days since prior procarbazine or major surgery At least 28 days since prior investigational agent or cytotoxic therapy At least 42 days since prior nitrosoureas or radiotherapy No prior sorafenib, AEE788, or vatalanib No prior surgical procedures affecting absorption No prior tipifarnib, lonafarnib, or other agents targeting farnesyl transferase (for patients receiving sorafenib and tipifarnib) No prior temsirolimus or mechanistic target of rapamycin (mTOR-targeting agent) (phase II), rapamycin or everolimus, or Akt-pathway inhibitors (for patients receiving sorafenib and temsirolimus) No prior erlotinib hydrochloride, multitargeted human epidermal receptor (AEE788), or other epidermal growth factor receptor targeting agents (phase II) (for patients receiving sorafenib and erlotinib hydrochloride) No concurrent enzyme-inducing antiepileptic drugs (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, or primidone) Dexamethasone allowed No concurrent hepatic cytochrome p450 enzyme-inducing anticonvulsants No other concurrent investigational agents or anticancer therapies, including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy No concurrent prophylactic filgrastim (G-CSF) or other hematopoietic colony-stimulating factors Full-dose anticoagulants allowed provided both of the following criteria are met: In-range INR (between 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

Sites / Locations

  • University of California at Los Angeles
  • University of California San Francisco
  • Dana-Farber Cancer Institute
  • Memorial Sloan-Kettering Cancer Center
  • University of Pittsburgh
  • M D Anderson Cancer Center
  • University of Wisconsin Hospital and Clinics

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.

Patients receive sorafenib tosylate as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

Patients receive sorafenib tosylate as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of the Each Combination Agent Combined With a Fixed Dose of BAY 43-9006 Determined by Dose-limiting Toxicities (DLT) (Phase I)
DLT defined as: any grade 4 hematologic toxicity; grade 3 thrombocytopenia > 7 days, any grade 3/4 non-hematologic toxicity (despite maximal medical therapy), any intolerable grade 2 non-hematological, ro grade 3 hematological toxicity requiring deduction during first 28 days of treatment, any toxicity resulting in delay of >1week during first 28 days of treatment
Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Group 2: 13 patients received temsirolimus 25mg IV and 7 patients treated with 200mg Sorafenib and 6 patients treated with 400mg Sorafenib
Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
8 samples collected over 24 hours on Day 1, day 15 and day 28 13 total patients treated 100mg Erlotinib and either 200mg or 400mg of Sorafenib
Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
8 samples collected over 24 hours on Day 1, day 15 and day 28 16 patients Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference AUC - Area Under Curve
Trough Concentration Group 2 Sorafenib and Temsirolimus (Phase I)
Group 2: 12 patients were analyzed for Day 1 (1 patient not evaluable), 5 patients were analyzed for Day 15 (8 patients not evaluable)
Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
Day 1 = 12 patients (1 sample not evaluable) Day 15 = 5 patients (8 samples not evaluable) AUC - Area Under Curve 8 samples collected over 24 hours - 28 day PKs
Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Group 3: Only PKs for Dose level 1 and -1 were collected.
Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Group 3: patients were studied for their day 1 Cmax, and day 15 Cmax Tipifanib and Day 15 and Day 28 sorafenib Group 3: Only PKs for Dose level 1 and -1 were collected.
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
Group 3: PKs for Dose level -1 100mg QD Note that although 9 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
Group 3: PKs for Dose level 1 Tipifarnib 100mg BID
12 Month Survival Rate (Phase II)
number of patients alive at 12 months
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
CTCAE 3.0
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Progression-free Survival at 6 Months (Phase II)
Patients with a scan at 6 months without progressive disease Progressive disease defined as Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.
Objective Response Rate in Patients With Measurable Disease (Phase II)
Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Secondary Outcome Measures

Full Information

First Posted
June 8, 2006
Last Updated
May 31, 2018
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00335764
Brief Title
Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Official Title
Phase I/II Studies of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib), R115777 (Tipifarnib) or CCI-779 (Temsirolimus) in Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I/II trial is studying the side effects and best dose of erlotinib, tipifarnib, and temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Sorafenib, erlotinib, tipifarnib, and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib and tipifarnib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib, tipifarnib, or temsirolimus may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: Phase 1 1. Determine the maximum tolerated dose (MTD) of tipifarnib, erlotinib hydrochloride, or temsirolimus in combination with a fixed dose of sorafenib in patients with recurrent glioblastoma multiforme or gliosarcoma who are not taking enzyme-inducing antiepileptic drugs. SECONDARY OBJECTIVES: Phase 1 and 2 Characterize the safety profile of the doublet combinations of tipifarnib-sorafenib, erlotinib hydrochloride-sorafenib, and temsirolimus-sorafenib in patients with recurrent glioblastoma multiforme or gliosarcoma. Characterize the pharmacokinetics of these doublet combinations, evaluating single-agent pharmacokinetics of each agent and the combination pharmacokinetics to determine drug-drug interactions. Phase 2 Determine the efficacy of each of the doublet combinations, in terms of 6-month progression-free survival, in patients with recurrent glioblastoma multiforme or gliosarcoma. Determine the efficacy of each of the doublet combinations, in terms of 12-month survival and objective tumor response, in patients with recurrent glioblastoma multiforme or gliosarcoma. TERTIARY OBJECTIVES: Phase 2 Perform exploratory correlative laboratory studies by examining tissue markers of signal transduction pathways by immunohistochemical analysis using tissue blocks obtained prior to initiation of protocol therapy, either from the time of diagnosis or subsequent tumor resection. Determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents. OUTLINE: This is a multicenter, phase I, dose-escalation study of tipifarnib, erlotinib hydrochloride, and temsirolimus followed by a phase II open-label study. PHASE I: Patients are sequentially assigned to 1 of 3 treatment groups. GROUP 1: Patients receive oral sorafenib twice daily and oral erlotinib hydrochloride once daily on days 1-28. GROUP 2: Patients receive sorafenib as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. GROUP 3: Patients receive sorafenib as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21. In all groups, treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. In each treatment group, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride (group 1), temsirolimus (group 2), or tipifarnib (group 3) sequentially until the maximum tolerated dose (MTD) is determined for each group. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy. PHASE II: Patients receive sorafenib as in phase I. Patients also receive erlotinib hydrochloride, temsirolimus, or tipifarnib as in phase I at the MTD determined in phase I. Tissue that was collected during a prior surgery is examined for biomarkers by immunohistochemistry (in patients enrolled in the phase II portion of the study). Biomarkers examined include epidermal growth factor receptor, Receptor tyrosine-protein kinase (HER-2), Protein kinase B (AKT), S6 ribosomal protein, and Receptor-linked tyrosine kinases (Erk). After completion of study treatment, patients are followed every 3 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Patients receive sorafenib tosylate as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Patients receive sorafenib tosylate as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21.
Intervention Type
Drug
Intervention Name(s)
sorafenib tosylate
Other Intervention Name(s)
BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN
Intervention Description
given orally
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
CP-358,774, erlotinib, OSI-774
Intervention Description
given orally
Intervention Type
Drug
Intervention Name(s)
tipifarnib
Other Intervention Name(s)
R115777, Zarnestra
Intervention Description
given orally
Intervention Type
Drug
Intervention Name(s)
temsirolimus
Other Intervention Name(s)
CCI-779, cell cycle inhibitor 779, Torisel
Intervention Description
IV administration
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of the Each Combination Agent Combined With a Fixed Dose of BAY 43-9006 Determined by Dose-limiting Toxicities (DLT) (Phase I)
Description
DLT defined as: any grade 4 hematologic toxicity; grade 3 thrombocytopenia > 7 days, any grade 3/4 non-hematologic toxicity (despite maximal medical therapy), any intolerable grade 2 non-hematological, ro grade 3 hematological toxicity requiring deduction during first 28 days of treatment, any toxicity resulting in delay of >1week during first 28 days of treatment
Time Frame
28 days
Title
Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Description
Group 2: 13 patients received temsirolimus 25mg IV and 7 patients treated with 200mg Sorafenib and 6 patients treated with 400mg Sorafenib
Time Frame
cycle 1 ((Day1, Day15, Day28)
Title
Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
Description
8 samples collected over 24 hours on Day 1, day 15 and day 28 13 total patients treated 100mg Erlotinib and either 200mg or 400mg of Sorafenib
Time Frame
28days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration)
Title
Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
Description
8 samples collected over 24 hours on Day 1, day 15 and day 28 16 patients Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference AUC - Area Under Curve
Time Frame
28Days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration) AUC 0-12
Title
Trough Concentration Group 2 Sorafenib and Temsirolimus (Phase I)
Description
Group 2: 12 patients were analyzed for Day 1 (1 patient not evaluable), 5 patients were analyzed for Day 15 (8 patients not evaluable)
Time Frame
15 days
Title
Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
Description
Day 1 = 12 patients (1 sample not evaluable) Day 15 = 5 patients (8 samples not evaluable) AUC - Area Under Curve 8 samples collected over 24 hours - 28 day PKs
Time Frame
Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)
Title
Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Description
Group 3: Only PKs for Dose level 1 and -1 were collected.
Time Frame
Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Title
Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Description
Group 3: patients were studied for their day 1 Cmax, and day 15 Cmax Tipifanib and Day 15 and Day 28 sorafenib Group 3: Only PKs for Dose level 1 and -1 were collected.
Time Frame
Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Title
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
Description
Group 3: PKs for Dose level -1 100mg QD Note that although 9 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Time Frame
Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)
Title
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
Description
Group 3: PKs for Dose level 1 Tipifarnib 100mg BID
Time Frame
Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Title
12 Month Survival Rate (Phase II)
Description
number of patients alive at 12 months
Time Frame
12 months
Title
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Description
CTCAE 3.0
Time Frame
28 days
Title
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Time Frame
1 year
Title
Progression-free Survival at 6 Months (Phase II)
Description
Patients with a scan at 6 months without progressive disease Progressive disease defined as Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.
Time Frame
6 months
Title
Objective Response Rate in Patients With Measurable Disease (Phase II)
Description
Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Time Frame
Up to 5 years
Other Pre-specified Outcome Measures:
Title
Exploratory Correlative Laboratory Studies (Phase II)
Description
Examination of tissue markers of signal transduction pathways by immunohistochemical analysis this was an exploratory measure and it was not explore due to the negative results of the rest of the study
Time Frame
28 days
Title
Molecular Targeted Combinations Correlative Study Initiative
Description
Determine the relationship between tumor and blood biomarkers and clinical outcome of patients this was more an exploratory correlative and was not completed due to the negative outcome of other parts of the study
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma Evidence of tumor progression by MRI or CT scan within the past 14 days AND on a steroid dose that has been stable for ≥ 5 days Patients who underwent prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by either positron emission tomography or thallium scanning, magnetic resonance (MR) spectroscopy, or surgical documentation of disease Recent resection of recurrent or progressive tumor allowed Residual disease is not required Treatment for any number of prior relapses, defined as disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial treatment), allowed (phase I) No more than 3 prior therapies (initial therapy and therapy for 2 relapses) (phase II) Each of the following is considered 1 relapse: Disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial therapy) Underwent a surgical resection for relapsed disease and received no anticancer therapy for up to 12 weeks after surgical resection AND then underwent a subsequent surgical resection Received prior therapy for a low-grade glioma, followed by a surgical diagnosis of glioblastoma Failed prior radiotherapy 15 unstained paraffin slides or 1 tissue block must be available from original surgery, definitive surgery, or surgery closest to the initiation of this study (phase II) Karnofsky performance status 60-100% White Blood Cell (WBC) ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL (transfusion allowed) Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) Total bilirubin normal Creatinine < 1.5 mg/dL Prothrombin time (PT)/ international normalized ratio (INR) ≤ 1.5 (INR < 3.0 for patients on anticoagulation therapy) INR < 1.1 times upper limit of normal (ULN) (for patients on prophylactic anticoagulation therapy [low-dose warfarin]) Fasting cholesterol < 350 mg/dL (for patients receiving temsirolimus and sorafenib) Fasting triglycerides < 400 mg/dL (for patients receiving temsirolimus and sorafenib) Well-controlled hypertension (e.g., systolic blood pressure ≤ 140 mm Hg or diastolic pressure ≤ 90 mm Hg) allowed Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for at least 2 weeks (women) or 3 months (men) after completion of study treatment No peripheral neuropathy > grade 1 (for patients receiving sorafenib and tipifarnib) No evidence of bleeding diathesis or coagulopathy No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for ≥ 3 years No significant traumatic injury within the past 21 days No active infection or serious medical illness that would preclude study treatment No condition that would impair ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation or active peptic ulcer disease) No HIV disease No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole or econazole) or a history of allergic reactions attributed to any compound of similar chemical or biological composition to tipifarnib (for patients receiving sorafenib and tipifarnib) No other disease that would obscure toxicity or dangerously alter drug metabolism Recovered from prior therapy At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) (radiosensitizer does not count) At least 14 days since prior vincristine At least 21 days since prior procarbazine or major surgery At least 28 days since prior investigational agent or cytotoxic therapy At least 42 days since prior nitrosoureas or radiotherapy No prior sorafenib, AEE788, or vatalanib No prior surgical procedures affecting absorption No prior tipifarnib, lonafarnib, or other agents targeting farnesyl transferase (for patients receiving sorafenib and tipifarnib) No prior temsirolimus or mechanistic target of rapamycin (mTOR-targeting agent) (phase II), rapamycin or everolimus, or Akt-pathway inhibitors (for patients receiving sorafenib and temsirolimus) No prior erlotinib hydrochloride, multitargeted human epidermal receptor (AEE788), or other epidermal growth factor receptor targeting agents (phase II) (for patients receiving sorafenib and erlotinib hydrochloride) No concurrent enzyme-inducing antiepileptic drugs (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, or primidone) Dexamethasone allowed No concurrent hepatic cytochrome p450 enzyme-inducing anticonvulsants No other concurrent investigational agents or anticancer therapies, including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy No concurrent prophylactic filgrastim (G-CSF) or other hematopoietic colony-stimulating factors Full-dose anticoagulants allowed provided both of the following criteria are met: In-range INR (between 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Gilbert, MD
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

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