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

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ClinicalTrials.gov Identifier: NCT00335764
Recruitment Status : Completed
First Posted : June 12, 2006
Results First Posted : July 2, 2018
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Interventions Drug: sorafenib tosylate
Drug: erlotinib hydrochloride
Drug: tipifarnib
Drug: temsirolimus
Enrollment 92
Recruitment Details patients enrolled from 2006 - 2009 Patients accrued from comprehensive outpatient cancer centers
Pre-assignment Details  
Arm/Group Title Group 1 Phase I Sorafenib and Erlotinib Group 2 Phase I Sorafenib and Temsirolimus Group 3 Phase I Sorafenib and Tipifarnib Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Hide Arm/Group Description

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

sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)

erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID

temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW

Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.

sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID

tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally 400mg BID

temsirolimus: IV administration 25mg IV QW

Period Title: Overall Study
Started 17 13 24 19 19
Completed 16 13 24 19 18
Not Completed 1 0 0 0 1
Reason Not Completed
wrong histology             1             0             0             0             1
Arm/Group Title Group 1 Phase I Sorafenib and Erlotinib Group 2 Phase I Sorafenib and Temsirolimus Group 3 Phase I Sorafenib and Tipifarnib Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus Total
Hide Arm/Group Description

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Patients receive sorafenib tosylate as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.

sorafenib tosylate: given orally

tipifarnib: given orally

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate 400 mg BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Total of all reporting groups
Overall Number of Baseline Participants 16 13 24 19 18 90
Hide Baseline Analysis Population Description
In Group 1 Phase 1 and Group 2 Phase 2 - each had a patient with wrong histology that made the patient ineligible and hence was not included in any of the analysis. Thus, total enrollment was 92 but only 90 evaluable patients
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 16 participants 13 participants 24 participants 19 participants 18 participants 90 participants
53
(36 to 70)
50
(32 to 59)
57
(27 to 76)
52
(30 to 76)
50
(24 to 64)
53
(24 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 13 participants 24 participants 19 participants 18 participants 90 participants
Female
7
  43.8%
4
  30.8%
8
  33.3%
10
  52.6%
9
  50.0%
38
  42.2%
Male
9
  56.3%
9
  69.2%
16
  66.7%
9
  47.4%
9
  50.0%
52
  57.8%
Karnofsky Performance Status Scale   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 13 participants 24 participants 19 participants 18 participants 90 participants
90
(70 to 100)
80
(60 to 100)
85
(60 to 100)
90
(60 to 100)
90
(60 to 100)
90
(60 to 100)
[1]
Measure Description: Higher score better 100 normal no complaints/disease 90 capable normal activity few symptoms/disease 80 normal activity, some difficulty some symptoms/signs 70 caring for self not capable normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death
1.Primary Outcome
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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
3+3 design due to excessive toxicities of Group 3 no DLT was defined for Group 3
Arm/Group Title Group 1 Phase I Sorafenib and Erlotinib QD Group 2 Phase I Sorafenib and Temsirolimus QW Group 3 Phase I Sorafenib and Tipifarnib BID
Hide Arm/Group Description:

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

sorafenib tosylate: given orally Dose Level 0: 200mg BID (fixed) Dose Level 1: 400mg BID (fixed)

erlotinib hydrochloride: given orally Dose Level 0: 100mg QD Dose Level 1: 100mg QD Dose Level 2: 150mg QD

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID

temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW Dose Level 2: 50mg IV QW Dose Level 3: 75mg IV QW Dose Level 4: 125mg IV QW Dose Level 5: 175mg IV QW

Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.

sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID

tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID

Overall Number of Participants Analyzed 16 13 24
Measure Type: Number
Unit of Measure: mg
100 25 NA [1] 
[1]
due to the excessive toxicities of Group 3 no DLT was defined
2.Primary Outcome
Title Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Group 2: total 13 patients were studied for their day 1 Cmax ,day 15 Cmax and day 28 Cmax Note that although 13 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Arm/Group Title Group 2 Phase I Temsirolimus 25mg QW Group 2 Phase I Sorafenib 200mg BID Group 2 Phase I Sorafenib 400mg BID
Hide Arm/Group Description:

Pt receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Patients receive sorafenib tosylate BID.

sorafenib tosylate: given orally

temsirolimus: IV administration 25mg

Patients receive sorafenib tosylate BID 200mg. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally 200mg

temsirolimus: IV administration 25mg

Patients receive sorafenib tosylate BID 400mg. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally 400mg

temsirolimus: IV administration 25mg

Overall Number of Participants Analyzed 13 7 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Cmax Number Analyzed 13 participants 7 participants 6 participants
530  (101) NA [1]   (NA) NA [1]   (NA)
Day 15 Cmax Number Analyzed 12 participants 4 participants 4 participants
616  (209) 4.04  (1.68) 7.49  (3.46)
Day 28 Cmax Number Analyzed 13 participants 4 participants 3 participants
NA [2]   (NA) 3.26  (1.34) 6.24  (4.03)
[1]
specimens not collected on day 1
[2]
specimens not collected on day 28
3.Primary Outcome
Title Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
8 samples collected over 24 hours on Day 1, day 15 and day 28 (0,1,2,4,6,8,12hr, & 24hr post administration). Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Arm/Group Title Group 1 Phase I Erlotinib 100mg QD Group 1 Phase I Sorafenib 200mg BID Group 1 Phase I Sorafenib 400mg BID
Hide Arm/Group Description:

Patients receive oral oral erlotinib hydrochloride 100 mg once daily on days 1-28. Pts also receive Sorafenib tosylate BID

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive oral sorafenib tosylate BID 200mg oral erlotinib hydrochloride once daily on days 1-28.

sorafenib tosylate: given orally 200mg

erlotinib hydrochloride: given orally

Patients receive oral sorafenib tosylate BID 400mg and oral erlotinib hydrochloride once daily on days 1-28.

sorafenib tosylate: given orally 400mg

erlotinib hydrochloride: given orally

Overall Number of Participants Analyzed 16 9 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
cMax Day 1 Number Analyzed 14 participants 9 participants 6 participants
443  (155) NA [1]   (NA) NA [1]   (NA)
cMax Day 15 Number Analyzed 16 participants 9 participants 6 participants
662  (373) 5.51  (2.68) 8.4  (5.18)
cMax Day 28 Number Analyzed 10 participants 7 participants 3 participants
653  (469) 4.67  (2.10) 4.10  (0.56)
[1]
Specimens not collected/drug not given on Day 1
4.Primary Outcome
Title Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
8 samples collected over 24 hours on Day 1, day 15 and day 28 AUC 0-12 16 patients treated at 100mg erlotinib,and Sorafenib at either 200 or 400mg Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Arm/Group Title Group 1 Phase I Erlotinib 100mg QD Group 1 Phase I Sorafenib 200mg Group 1 Phase I Sorafenib 400mg
Hide Arm/Group Description:

Patients receive oral erlotinib hydrochloride 100 mg once daily on days 1-28.And also oral sorafenib tosylate BID

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive oral sorafenib tosylate BID 200mg and oral erlotinib hydrochloride once daily on days 1-28.

sorafenib tosylate: given orally 200mg

erlotinib hydrochloride: given orally

Patients receive oral sorafenib tosylate BID 400mg and oral erlotinib hydrochloride once daily on days 1-28.

sorafenib tosylate: given orally 400mg

erlotinib hydrochloride: given orally

Overall Number of Participants Analyzed 16 9 6
Mean (Standard Deviation)
Unit of Measure: ug xhr/mL
AUC0-12 Day1 Number Analyzed 14 participants 9 participants 6 participants
6.3  (2.61) NA [1]   (NA) NA [1]   (NA)
AUC0-12 Day 15 Number Analyzed 6 participants 9 participants 5 participants
6.9  (4.59) 45.85  (21.5) 62.4  (38)
AUC0-12 Day 28 Number Analyzed 8 participants 7 participants 3 participants
7.7  (4.05) 40.29  (18.6) 38.7  (9.61)
[1]
Specimens not collected/drug not given on Day 1
5.Primary Outcome
Title Trough Concentration Group 2 Sorafenib and Temsirolimus (Phase I)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Group 2: 12 patients were analyzed for Day 1, 5 patients were analyzed for Day 15. In both cases samples were either missing or not enough to analyze.
Arm/Group Title Group 2 Phase I Sorafenib and Temsirolimus QW
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

temsirolimus: IV administration

Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: ng/mL
Trough Day 1 Number Analyzed 12 participants
24  (6.92)
Trough Day 15 Number Analyzed 5 participants
20  (7.05)
6.Primary Outcome
Title Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
13 patients temsirolimus 25mg and Sorafenib at either 200mg or 400mg. 1 patient withdrew early hence specimens not analyzed in other cases samples were either missing or not enough to analyze if numbers are not 12
Arm/Group Title Group 2 Phase I Temsirolimus 25mg QW Group 2 Phase I Sorafenib 200mg Group 2 Phase I Sorafenib 400mg
Hide Arm/Group Description:

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

sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID

temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW

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

sorafenib tosylate: given orally Dose Level 0: 200mg BID

temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW

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

sorafenib tosylate: given orally Dose Level 1: 400mg BID

temsirolimus: IV administration Dose Level 0: 25mg IV QW Dose Level 1: 25mg IV QW

Overall Number of Participants Analyzed 13 13 13
Mean (Standard Deviation)
Unit of Measure: mcg*hr/mL
AUC 0-12 Day 1 Number Analyzed 12 participants 13 participants 13 participants
1.53  (0.27) NA [1]   (NA) NA [1]   (NA)
AUC 0-12 Day 15 Number Analyzed 5 participants 3 participants 1 participants
1.35  (0.28) 35.45  (18.10) 42.32
AUC 0-12 Day 28 Number Analyzed 13 participants 13 participants 2 participants
NA [2]   (NA) 29.0  (12.32) 32.98  (0.318)
[1]
Samples not collected on this day, drug not given on day 1
[2]
Samples not collected on this day, drug not given on day 28
7.Primary Outcome
Title Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Group 3: Only PKs for Dose level 1 and -1 were collected. Note that although 6 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Arm/Group Title Group 3 Phase I Tipifarnib 100mg QD Group 3 Phase I Sorafenib 200mg BID
Hide Arm/Group Description:

Patients receive oral tipifarnib every day on days 1-21. Patients also receive sorafenib tosylate BID

sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose level -1: 100mg QD

Patients receive sorafenib tosylate BID Patients also receive oral tipifarnib every day on days 1-21.

sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose level -1: 100mg QD

Overall Number of Participants Analyzed 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cmax Day 1 Number Analyzed 6 participants 3 participants
209.5  (135.85) NA [1]   (NA)
Cmax Day 15 Number Analyzed 6 participants 3 participants
169.5  (186) 3.34  (1.31)
Cmax Day 28 Number Analyzed 6 participants 6 participants
NA [2]   (NA) 3.43  (1.46)
[1]
Samples not collected on day 1, drug not given on day 1
[2]
Samples not collected on day 28, drug not given on day 28
8.Primary Outcome
Title Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description

Group 3: patients were studied for their day 1 Cmax, day 15 Cmax. and Day 28 Cmax PKs for 100mg BID Tipifarnib Note that although 10 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference

Level 1 (n=10): Day 1 n=6 (4 samples not evaluable) and D15 n=5 (5 samples not evaluable)

Arm/Group Title Group 3 Phase I Tipifarnib 100mg BID Group 3 Phase I Sorafenib 200mg BID
Hide Arm/Group Description:

Patients receive oral tipifarnib 100mg twice daily on days 2-21. Patients also sorafenib tosylate BID 200mg

sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose Level 1: 100mg BID

Patients receive oral tipifarnib 100mg twice daily on days 2-21. Patients also sorafenib tosylate BID 200mg

sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose Level 1: 100mg BID

Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Cmax Number Analyzed 6 participants 10 participants
132.17  (65.96) NA [1]   (NA)
Day 15 Cmax Number Analyzed 5 participants 5 participants
233.60  (84.83) 4.17  (2.99)
Day 28 Cmax Number Analyzed 10 participants 7 participants
NA [1]   (NA) 4.53  (2.38)
[1]
Samples not collected on this day, drug not given
9.Primary Outcome
Title Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Group 3: PKs for Dose level -1 Tipifarnib 100mg QD Sorafenib started day 2
Arm/Group Title Group 3 Phase I Tipifarnib 100mg QD Group 3 Phase I Sorafenib 200mg BID
Hide Arm/Group Description:

Patients receive oral tipifarnib 100mg twice daily on days 1-21. also receive sorafenib tosylate BID100mg

sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose Level -1: 100mg QD

Patients receive sorafenib tosylate BID100mgal and also tipifarnib 100mg QD on days 1-21.sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose Level -1: 100mg QD

Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
AUC 0-12 Day 1 Number Analyzed 6 participants 9 participants
814.5  (347.57) NA [1]   (NA)
AUC 0-12 Day 15 Number Analyzed 2 participants 3 participants
706  (644.88) 30.59  (14.59)
AUC 0-12 Day 28 Number Analyzed 9 participants 9 participants
NA [1]   (NA) 41.43  (28.82)
[1]
Samples not collected on this day, drug not given
10.Primary Outcome
Title Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Group 3: PKs for Dose level 1 Tipifarnib 100mg BID
Arm/Group Title Group 3 Phase I Tipifarnib 100mg QD Group 3 Phase I Sorefenib 200mg BID
Hide Arm/Group Description:

Patients receive oral tipifarnib twice daily on days 1-21. Patients also receive sorafenib tosylate BID 200 mg starting on day 2

sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose Level 1: 100mg BID

Patients also receive sorafenib tosylate BID 200 mg starting on day 2. Patients receive oral tipifarnib twice daily on days 1-21.

sorafenib tosylate: given orally Dose Level 0: 200mg BID

tipifarnib: given orally Dose Level 1: 100mg BID

Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
AUC 0-12 Day 1 Number Analyzed 6 participants 10 participants
631.67  (431.12) NA [1]   (NA)
AUC 0-12 Day 15 Number Analyzed 4 participants 2 participants
390.25  (758.07) 12.17  (16.33)
AUC 0-12 Day 28 Number Analyzed 10 participants 7 participants
NA [1]   (NA) 36.45  (17.21)
[1]
Samples not collected, drug not given on this day
11.Primary Outcome
Title 12 Month Survival Rate (Phase II)
Hide Description number of patients alive at 12 months
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Group 3 did not reach an MTD Hence, did not complete the Phase 2 portion of study, combination treatment too toxic.
Arm/Group Title Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Overall Number of Participants Analyzed 19 18
Measure Type: Count of Participants
Unit of Measure: Participants
Patients Alive at 12 Months
8
  42.1%
10
  55.6%
Patients Dead at 12 Months
11
  57.9%
8
  44.4%
12.Primary Outcome
Title Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Hide Description CTCAE 3.0
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Phase I Sorafenib and Erlotinib QD Group 2 Phase I Sorafenib and Temsirolimus QW Group 3 Phase I Sorafenib and Tipifarnib BID
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.

sorafenib tosylate: given orally

tipifarnib: given orally

Overall Number of Participants Analyzed 16 13 24
Measure Type: Number
Unit of Measure: Events
Leukopenia Grade 3 0 0 0
Lymphopenia Grade 3 0 2 3
Neutropenia Grade 3 0 0 0
Thrombocytopenia Grade 3 0 1 0
AST, SGOT Grade 3 1 1 0
Cholesterol Grade 3 0 1 0
Diarrhea Grade 3 0 1 2
Hemmorrhoids Grade 3 0 1 0
Hypertriglyceridemia Grade 3 0 1 0
Hypophosphatemia Grade 3 3 2 4
Fatigue Grade 3 0 0 1
Vomiting Grade 3 0 0 1
Lipase Grade 4 0 0 3
Joint - Knee Pain Grade 3 0 0 1
Thrombosis/thrombus/embolism Grade 4 0 0 1
Fever Grade 3 0 0 1
Dysphasia Grade 3 0 0 1
Pain - Head/Headache Grade 3 0 0 1
Encephalopathy Grade 3 0 0 1
Lipase Grade 3 1 0 0
ALT, SGPT Grade 3 2 0 0
Hypertension Grade 3 1 0 0
13.Primary Outcome
Title Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Hide Description [Not Specified]
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Overall Number of Participants Analyzed 19 18
Measure Type: Number
Unit of Measure: events
Lymphopenia Grade 3 2 2
Thrombocytopenia Grade 3 0 5
Thrombocytopenia Grade 4 0 2
Cholesterol (high) Grade 3 0 2
Diarrhea Grade 3 1 1
Fatigue Grade 3 3 2
Hypokalemia Grade 3 0 1
Hyponatremia Grade 3 0 1
Hypophosphatemia Grade 3 0 3
Lipase (high) Grade 3 0 1
Pharyngeal mucositis Grade 3 0 1
Pruritis Grade 3 0 1
Rash Grade 3 0 1
Seizures Grade 3 0 1
Hypertension Grade 3 1 0
14.Primary Outcome
Title Progression-free Survival at 6 Months (Phase II)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Group 3 did not reach an MTD not complete the Phase 2 portion of study, combination treatment too toxic. End points not followed for group 3 Phase 2
Arm/Group Title Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus Group 3 Phase I Sorafenib and Tipifarnib BID
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Patients receive sorafenib tosylate BID as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.

sorafenib tosylate: given orally Dose Level 0: 200mg BID Dose Level 1: 400mg BID

tipifarnib: given orally Dose Level 0: 100mg BID Dose Level 1: 100mg BID Dose Level 2: 200mg BID Dose Level 3: 300mg BID

Overall Number of Participants Analyzed 19 18 24
Mean (95% Confidence Interval)
Unit of Measure: weeks
15.8
(3.4 to 39.6)
8
(5 to 9)
4.2
(0.1 to 21.1)
15.Primary Outcome
Title Objective Response Rate in Patients With Measurable Disease (Phase II)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Overall Number of Participants Analyzed 19 18
Measure Type: Count of Participants
Unit of Measure: Participants
Partial Response
0
   0.0%
2
  11.1%
Complete Response
0
   0.0%
0
   0.0%
Stable Response
7
  36.8%
3
  16.7%
Progressive Disease
10
  52.6%
13
  72.2%
Unevaluable
2
  10.5%
0
   0.0%
16.Other Pre-specified Outcome
Title Exploratory Correlative Laboratory Studies (Phase II)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
this was more an exploratory correlative and as per the pre-specified protocol, was only to be performed if the outcome of other parts of the study indicated positive results.
Arm/Group Title Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
17.Other Pre-specified Outcome
Title Molecular Targeted Combinations Correlative Study Initiative
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
This was more an exploratory correlative and as per the pre-specified protocol, was only to be performed if the outcome of other parts of the study indicated positive results.
Arm/Group Title Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Hide Arm/Group Description:

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 2 years
Adverse Event Reporting Description CTCAE
 
Arm/Group Title Group 1 Phase I Sorafenib and Erlotinib Group 2 Phase I Sorafenib and Temsirolimus Group 3 Phase I Sorafenib and Tipifarnib Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Hide Arm/Group Description

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate as in group 2. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

Patients receive sorafenib tosylate as in group 3. Patients also receive oral tipifarnib twice daily on days 1-21.

sorafenib tosylate: given orally

tipifarnib: given orally

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

sorafenib tosylate: given orally

erlotinib hydrochloride: given orally

Patients receive sorafenib tosylate 400 mg BID as in group 2. Patients also receive temsirolimus IV 25 mg over 30 minutes on days 1, 8, 15, and 22.

sorafenib tosylate: given orally

temsirolimus: IV administration

All-Cause Mortality
Group 1 Phase I Sorafenib and Erlotinib Group 2 Phase I Sorafenib and Temsirolimus Group 3 Phase I Sorafenib and Tipifarnib Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/16 (93.75%)      13/13 (100.00%)      24/24 (100.00%)      19/19 (100.00%)      18/18 (100.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Group 1 Phase I Sorafenib and Erlotinib Group 2 Phase I Sorafenib and Temsirolimus Group 3 Phase I Sorafenib and Tipifarnib Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      0/13 (0.00%)      4/24 (16.67%)      1/19 (5.26%)      2/18 (11.11%)    
Gastrointestinal disorders           
Abdominal pain * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Diarrhea * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 1/18 (5.56%)  1
Infections and infestations           
Pancrease infection * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Investigations           
Lipase increased * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Serum amylase increased * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Metabolism and nutrition disorders           
Hypertriglyceridemia * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Nervous system disorders           
Encephalopathy * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Headache * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Seizure * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Psychiatric disorders           
Confusion * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 1/19 (5.26%)  1 0/18 (0.00%)  0
Skin and subcutaneous tissue disorders           
Rash acneiform * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Vascular disorders           
Hypertension * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Thromboembolic event * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1 Phase I Sorafenib and Erlotinib Group 2 Phase I Sorafenib and Temsirolimus Group 3 Phase I Sorafenib and Tipifarnib Group 1 Phase II Sorafenib and Erlotinib Group 2 Phase II Sorafenib and Temsirolimus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/16 (81.25%)      8/13 (61.54%)      15/24 (62.50%)      11/19 (57.89%)      12/18 (66.67%)    
Blood and lymphatic system disorders           
Anemia * 1  0/16 (0.00%)  0 4/13 (30.77%)  4 3/24 (12.50%)  3 1/19 (5.26%)  1 4/18 (22.22%)  4
Ear and labyrinth disorders           
Ear and labyrinth disorders - Other, specify * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Eye disorders           
Watering eyes * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Gastrointestinal disorders           
Acidosis * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Constipation * 1  0/16 (0.00%)  0 2/13 (15.38%)  2 3/24 (12.50%)  3 1/19 (5.26%)  1 0/18 (0.00%)  0
Diarrhea * 1  4/16 (25.00%)  4 4/13 (30.77%)  4 0/24 (0.00%)  0 2/19 (10.53%)  2 2/18 (11.11%)  2
Dyspepsia * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Muscositis oral * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 3/18 (16.67%)  3
Nausea * 1  2/16 (12.50%)  2 0/13 (0.00%)  0 2/24 (8.33%)  2 2/19 (10.53%)  2 2/18 (11.11%)  2
Oral pain * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Vomiting * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
General disorders           
Chills * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Fatigue * 1  3/16 (18.75%)  3 2/13 (15.38%)  2 7/24 (29.17%)  7 6/19 (31.58%)  6 3/18 (16.67%)  3
Infections and infestations           
Lung infection * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Nail infection * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Investigations           
Alanine aminotransferase increased * 1  3/16 (18.75%)  3 2/13 (15.38%)  2 2/24 (8.33%)  2 3/19 (15.79%)  3 3/18 (16.67%)  3
Alkaline phosphatase increased * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Aspartate aminotransferase increased * 1  4/16 (25.00%)  4 2/13 (15.38%)  2 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Blood bilirubin increased * 1  0/16 (0.00%)  0 2/13 (15.38%)  2 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Cholesterol high * 1  0/16 (0.00%)  0 3/13 (23.08%)  3 0/24 (0.00%)  0 0/19 (0.00%)  0 5/18 (27.78%)  5
Lipase increased * 1  5/16 (31.25%)  5 1/13 (7.69%)  1 4/24 (16.67%)  4 1/19 (5.26%)  1 0/18 (0.00%)  0
Lymphocyte count decreased * 1  2/16 (12.50%)  2 0/13 (0.00%)  0 4/24 (16.67%)  4 3/19 (15.79%)  3 5/18 (27.78%)  5
Neutrophil count decreased * 1  2/16 (12.50%)  2 1/13 (7.69%)  1 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Platelet count decreased * 1  3/16 (18.75%)  3 5/13 (38.46%)  5 0/24 (0.00%)  0 2/19 (10.53%)  2 7/18 (38.89%)  7
Serum amylase increased * 1  2/16 (12.50%)  2 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Weight loss * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 2/19 (10.53%)  2 0/18 (0.00%)  0
White blood cell count decreased * 1  6/16 (37.50%)  6 3/13 (23.08%)  3 3/24 (12.50%)  3 1/19 (5.26%)  1 1/18 (5.56%)  1
Metabolism and nutrition disorders           
Anorexia * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 2/19 (10.53%)  2 0/18 (0.00%)  0
Hypercalcemia * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Hyperglycemia * 1  2/16 (12.50%)  2 1/13 (7.69%)  1 5/24 (20.83%)  5 1/19 (5.26%)  1 3/18 (16.67%)  3
Hyperkalemia * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Hypermagnesemia * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Hypernatremia * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Hypertriglyceridemia * 1  0/16 (0.00%)  0 4/13 (30.77%)  4 0/24 (0.00%)  0 0/19 (0.00%)  0 4/18 (22.22%)  4
Hypoalbuminemia * 1  2/16 (12.50%)  2 1/13 (7.69%)  1 2/24 (8.33%)  2 1/19 (5.26%)  1 0/18 (0.00%)  0
Hypocalcemia * 1  1/16 (6.25%)  1 1/13 (7.69%)  1 5/24 (20.83%)  5 0/19 (0.00%)  0 3/18 (16.67%)  3
Hypokalemia * 1  3/16 (18.75%)  3 1/13 (7.69%)  1 0/24 (0.00%)  0 1/19 (5.26%)  1 2/18 (11.11%)  2
Hypomagnesemia * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 2/18 (11.11%)  2
Hyponatremia * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 2/24 (8.33%)  2 0/19 (0.00%)  0 1/18 (5.56%)  1
Hypophosphatemia * 1  4/16 (25.00%)  4 3/13 (23.08%)  3 2/24 (8.33%)  2 3/19 (15.79%)  3 4/18 (22.22%)  4
Metabolism and nutrition disorders - Other, specify * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Chest wall pain * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Generalized Muscle Weakness * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Myalgia * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Nervous system disorders           
Dizziness * 1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Headache * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Peripheral sensory neuropathy * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 1/18 (5.56%)  1
Psychiatric disorders           
Confusion * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Depression * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 1/18 (5.56%)  1
Renal and urinary disorders           
Hemoglobinuria * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Cough * 1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Pharyngeal mucositis * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Skin and subcutaneous tissue disorders           
Alopecia * 1  2/16 (12.50%)  2 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Bruising * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Dry Skin * 1  1/16 (6.25%)  1 2/13 (15.38%)  2 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Nail loss * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Palmar-plantar erythrodysesthesia syndrome * 1  2/16 (12.50%)  2 0/13 (0.00%)  0 0/24 (0.00%)  0 2/19 (10.53%)  2 1/18 (5.56%)  1
Pruritus * 1  2/16 (12.50%)  2 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Purpura * 1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Rash acneiform * 1  2/16 (12.50%)  2 0/13 (0.00%)  0 0/24 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Rash maculo-papular * 1  4/16 (25.00%)  4 2/13 (15.38%)  2 2/24 (8.33%)  2 5/19 (26.32%)  5 3/18 (16.67%)  3
Vascular disorders           
Hypertension * 1  2/16 (12.50%)  2 1/13 (7.69%)  1 0/24 (0.00%)  0 1/19 (5.26%)  1 1/18 (5.56%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Due to combo toxicities for Sorafenib and Tipifarnib exceeding monotherapy for each, MTD was not determined nor was Phase 2 explored.
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.
Results Point of Contact
Name/Title: Mark Gilbert, MD
Organization: Adult Brain Tumor Consortium (ABTC)
Phone: 410-955-3657
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00335764     History of Changes
Other Study ID Numbers: NCI-2009-00676
NCI-2009-00676 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000476286
NABTC-05-02 ( Other Identifier: Adult Brain Tumor Consortium )
NABTC-05-02 ( Other Identifier: CTEP )
U01CA137443 ( U.S. NIH Grant/Contract )
First Submitted: June 8, 2006
First Posted: June 12, 2006
Results First Submitted: August 16, 2017
Results First Posted: July 2, 2018
Last Update Posted: July 2, 2018