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Trial record 5 of 11 for:    "Undifferentiated Pleomorphic Sarcoma" | "Immunologic Factors"

A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma

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ClinicalTrials.gov Identifier: NCT00667342
Recruitment Status : Completed
First Posted : April 28, 2008
Results First Posted : August 4, 2014
Last Update Posted : June 28, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Osteosarcoma
Malignant Fibrous Histiocytoma (MFH) of Bone
Interventions Biological: Bevacizumab
Drug: Cisplatin
Drug: Doxorubicin
Drug: Methotrexate
Drug: Ifosfamide
Drug: etoposide
Procedure: Surgery
Radiation: Radiotherapy
Enrollment 43
Recruitment Details Forty-three participants were enrolled between June 2008 and May 2012: 34 at St. Jude Children's Research Hospital, 6 at Rady Children's Hospital San Diego, 2 at Johns Hopkins University Hospital, and 1 at M.D. Anderson in Houston
Pre-assignment Details All participants had newly diagnosed high-grade, biopsy-proven osteosarcoma, or malignant fibrous histiocytoma (MFH) of bone
Arm/Group Title A: Localized Resectable Disease B: Localized Unresectable Disease C: Metastatic Tumors
Hide Arm/Group Description Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis. Participants with localized unresectable primary tumors were to participate in Stratum B. No participants were enrolled to this stratum. Stratum C participants had metastatic tumors.
Period Title: Overall Study
Started 31 0 12
Completed 17 0 3
Not Completed 14 0 9
Reason Not Completed
Protocol Violation             1             0             0
Withdrawal by Subject             1             0             0
Physician Decision             3             0             0
Relapse or tumor progression             9             0             7
Adverse Event             0             0             1
Ineligible             0             0             1
Arm/Group Title A: Localized Resectable Disease B: Localized Unresectable Disease C: Metastatic Tumors Total
Hide Arm/Group Description Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis. Participants with localized unresectable primary tumors were to participate in Stratum B. No participants were enrolled to this stratum. Stratum C participants had metastatic tumors. Total of all reporting groups
Overall Number of Baseline Participants 31 0 12 43
Hide Baseline Analysis Population Description
Participants were eligible if they were ≤30 years of age on date of diagnostic biopsy confirmation of high-grade osteosarcoma or malignant fibrous histiocytoma (MFH) of bone. Participants had no previous chemotherapy or radiation therapy.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 0 participants 12 participants 43 participants
12.7  (3.5) 13.3  (4.2) 12.9  (3.6)
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 31 participants 0 participants 12 participants 43 participants
12
(6 to 20)
12
(8 to 20)
12
(6 to 20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 0 participants 12 participants 43 participants
Female
15
  48.4%
5
  41.7%
20
  46.5%
Male
16
  51.6%
7
  58.3%
23
  53.5%
1.Primary Outcome
Title Number of Participants With Unacceptable Toxicity
Hide Description

Objective: To study the feasibility of combining: 1) bevacizumab with cisplatin, doxorubicin, and high-dose methotrexate (MAP) in patients with localized resectable osteosarcoma; and 2) bevacizumab with MAP and ifosfamide, and etoposide in patients with unresectable or metastatic osteosarcoma.

The target unacceptable toxicity is defined as grade 4 hypertension, proteinuria, or bleeding excluding petechiae/purpura, grade 3/4 thrombosis/embolism excluding catheter-related thrombosis. The unacceptable toxicity for major wound complication is defined as grade 2, 3, or 4 major wound complications.

A six-stage group sequential stopping rule was developed for monitoring unacceptable toxicity.

Time Frame After all patients have completed therapy, up to 1 year after last patient is enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
Due to slow accrual, the trial was closed to accrual early. Thus, only 31 stratum A patients and 12 stratum B or C patients were enrolled on the study. Therefore, based on the number of patients enrolled and the designed power for the study, we do not have confidence in making a conclusion regarding this feasibility objective.
Arm/Group Title A: Localized Resectable Disease C: Metastatic Tumors
Hide Arm/Group Description:
Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Stratum C participants had metastatic tumors.
Overall Number of Participants Analyzed 31 11
Measure Type: Number
Unit of Measure: participants
Grade 4 Hypertension 0 0
Grade 4 Proteinuria 0 0
Grade 4 Bleeding 0 0
Grade 3/4 Thrombosis/Embolism 1 0
Grade 2, 3 or 4 Major Wound Complication 7 2
2.Primary Outcome
Title 3-Year Event Free Survival
Hide Description To study the effect of adding bevacizumab to chemotherapy comprised of cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) on the event-free survival (EFS) in patients with localized resectable osteosarcoma. The Kaplan-Meier (K-M) method was used to estimate survival rate.
Time Frame After all patients have completed therapy, up to 4 years after last patient is enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A: Localized Resectable Disease
Hide Arm/Group Description:
OS2008 Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Overall Number of Participants Analyzed 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
0.575
(0.402 to 0.747)
3.Secondary Outcome
Title Histologic Response by Stratum
Hide Description

The effect of adding bevacizumab to preoperative chemotherapy comprised of cisplatin, doxorubicin, and HDMTX on the histologic response in patients with localized resectable osteosarcoma compared to historical controls treated with preoperative cisplatin, doxorubicin, and HDMTX without bevacizumab on the Intergroup Study 0133.

Histologic response at week 10 of therapy was evaluated by Huvos grading systems as grade I: tumor not responding to therapy, no effect identified; grade IIA: more than 50% viable tumor left; grade IIB: 5-50% viable tumor remaining; grade III: only scattered foci of viable tumor seen (less than 5% of tumor); grade IV: no viable tumor seen in extensive sampling (at least a full cross-section of the tumor).

The study did not enroll an adequate number of participants, therefore, the comparison to Intergroup Study 0133 participants was not done.

Time Frame After 6 cycles of chemotherapy, up to 1 year after the start of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
All Stratum A participants were evaluated. The tumor sample for analysis was not obtained for one of the 12 Stratum C participants.
Arm/Group Title A: Localized Resectable Disease C: Metastatic Tumors
Hide Arm/Group Description:
Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Stratum C participants had metastatic tumors.
Overall Number of Participants Analyzed 31 11
Measure Type: Number
Unit of Measure: participants
Grade I 1 0
Grade IIA 5 1
Grade IIB 17 7
Grade III 8 3
4.Secondary Outcome
Title 2-Year Event Free Survival (EFS) of Patients With Osteosarcoma
Hide Description Kaplan-Meier method was used to estimate the EFS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.
Time Frame After all patients have completed therapy, up to 2 years after last patient is enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
All the 42 evaluable participants were included in this analysis.
Arm/Group Title All Participants
Hide Arm/Group Description:
All the 42 evaluable participants in this study had osteosarcoma, of which 22 had events and 20 had no event.
Overall Number of Participants Analyzed 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
0.617
(0.470 to 0.764)
5.Secondary Outcome
Title 2-Year Overall Survival (OS) of Patients With Osteosarcoma
Hide Description Kaplan-Meier method was used to estimate the OS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.
Time Frame After all patients have completed therapy, up to 2 years after last patient is enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
All the 42 evaluable participants in this study had osteosarcoma, of which 12 died and 20 were still alive as of 05/04/2015.
Arm/Group Title All Participants
Hide Arm/Group Description:
All 42 evaluable participants were included in this analysis
Overall Number of Participants Analyzed 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
0.880
(0.782 to 0.978)
6.Secondary Outcome
Title 2-Year Event Free Survival (EFS) in Patients With Localized Resectable Disease Compared to St. Jude OS99 Protocol.
Hide Description The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS20008 to that of OS99 (NCT00145639) participants was not done. The 2-year EFS of OS2008 participants is reported here.
Time Frame After all patients have completed therapy, up to 2 years after last patient is enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
OS2008 Localized Resectable Disease group had 31 participants: 14 had events, 17 had no events.
Arm/Group Title A: Localized Resectable Disease
Hide Arm/Group Description:
OS2008 Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Overall Number of Participants Analyzed 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
0.642
(0.473 to 0.810)
7.Secondary Outcome
Title 2-Year Overall Survival (OS) in Patients With Localized Resectable Disease Compared to OS99 Protocol.
Hide Description The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS2008 to that of OS99 (NCT00145639) participants was not done. The 2-year OS of OS2008 participants is reported here.
Time Frame After all patients have completed therapy, up to 2 years after last patient is enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
OS2008 Localized Resectable Disease group had 31 participants: 7 were expired and 24 still alive
Arm/Group Title A: Localized Resectable Disease
Hide Arm/Group Description:
OS2008 Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Overall Number of Participants Analyzed 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
0.934
(0.847 to 1.0)
8.Secondary Outcome
Title Mean Ktrans
Hide Description The volume transfer constant (Ktrans) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Time Frame Baseline through Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed at each time point differed due to missing observations at some of the time points
Arm/Group Title A: Localized Resectable Disease C: Metastatic Tumors
Hide Arm/Group Description:
Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Stratum C participants had metastatic tumors.
Overall Number of Participants Analyzed 31 11
Mean (Standard Deviation)
Unit of Measure: min(-1)
Baseline Number Analyzed 26 participants 9 participants
0.13  (0.04) 0.15  (0.07)
Day -2 Number Analyzed 21 participants 6 participants
0.11  (0.05) 0.14  (0.03)
Day 1 Number Analyzed 21 participants 6 participants
0.12  (0.06) 0.16  (0.04)
Day 5 Number Analyzed 24 participants 8 participants
0.14  (0.06) 0.16  (0.04)
Week 5 Number Analyzed 28 participants 11 participants
0.08  (0.04) 0.10  (0.05)
Week 10 Number Analyzed 27 participants 11 participants
0.07  (0.05) 0.07  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: Localized Resectable Disease
Comments [Not Specified]
Type of Statistical Test Other
Comments The association between response and Ktrans at Week 10 was evaluated.
Statistical Test of Hypothesis P-Value 0.0863
Comments [Not Specified]
Method Logistic Regression
Comments [Not Specified]
9.Secondary Outcome
Title Mean Vp
Hide Description The fractional blood plasma volume (Vp) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Time Frame Baseline through Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed at each time point differed due to missing observations at some of the time points
Arm/Group Title A: Localized Resectable Disease C: Metastatic Tumors
Hide Arm/Group Description:
Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Stratum C participants had metastatic tumors.
Overall Number of Participants Analyzed 31 11
Mean (Standard Deviation)
Unit of Measure: (unitless)
Baseline Number Analyzed 26 participants 9 participants
0.0081  (0.0024) 0.0094  (0.0016)
Day -2 Number Analyzed 21 participants 6 participants
0.0067  (0.0020) 0.0077  (0.0022)
Day 1 Number Analyzed 21 participants 6 participants
0.0070  (0.0027) 0.0095  (0.0027)
Day 5 Number Analyzed 24 participants 8 participants
0.0066  (0.0033) 0.0089  (0.0029)
Week 5 Number Analyzed 28 participants 11 participants
0.0063  (0.0029) 0.0069  (0.0032)
Week 10 Number Analyzed 27 participants 11 participants
0.0060  (0.0044) 0.0055  (0.0026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: Localized Resectable Disease
Comments [Not Specified]
Type of Statistical Test Other
Comments The association between response and Vp at Week 10 was evaluated.
Statistical Test of Hypothesis P-Value 0.0573
Comments [Not Specified]
Method Logistic Regression
Comments [Not Specified]
10.Secondary Outcome
Title Mean Ve
Hide Description The fractional volume of extravascular extracellular space (Ve) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Time Frame Baseline through Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed at each time point differed due to missing observations at some of the time points
Arm/Group Title A: Localized Resectable Disease C: Metastatic Tumors
Hide Arm/Group Description:
Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.
Stratum C participants had metastatic tumors.
Overall Number of Participants Analyzed 31 11
Mean (Standard Deviation)
Unit of Measure: (unitless)
Baseline Number Analyzed 26 participants 9 participants
0.2543  (0.0785) 0.2671  (0.0888)
Day -2 Number Analyzed 21 participants 6 participants
0.2444  (0.0871) 0.2623  (0.0781)
Day 1 Number Analyzed 21 participants 6 participants
0.2564  (0.1209) 0.2602  (0.0447)
Day 5 Number Analyzed 24 participants 8 participants
0.2854  (0.1138) 0.3126  (0.0727)
Week 5 Number Analyzed 28 participants 11 participants
0.3055  (0.1622) 0.3105  (0.1425)
Week 10 Number Analyzed 27 participants 11 participants
0.2776  (0.1225) 0.2726  (0.1596)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: Localized Resectable Disease
Comments [Not Specified]
Type of Statistical Test Other
Comments The association between response and Ve at Week 10 was evaluated.
Statistical Test of Hypothesis P-Value 0.0863
Comments [Not Specified]
Method Logistic Regression
Comments [Not Specified]
11.Secondary Outcome
Title Histologic Response by Number of Participants
Hide Description The association of interested variables with response was checked with the Wilcoxon rank-sum test. The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
Time Frame at week 10 after start of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Two Stratum A participants with no histologic response were excluded.
Arm/Group Title All Participants
Hide Arm/Group Description:
All 42 evaluable participants in this study had osteosarcoma. This analysis includes 29 Stratum A participants who had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis, and 11 Stratum C participants who had metastatic tumors.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
Poor Response
22
  55.0%
Good Response
18
  45.0%
12.Secondary Outcome
Title Ktrans by Good and Poor Response
Hide Description The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
Time Frame at week 10 after start of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Two Stratum A participants with no histologic response were excluded.
Arm/Group Title All Participants
Hide Arm/Group Description:
All 42 evaluable participants in this study had osteosarcoma. This analysis includes 29 Stratum A participants who had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis, and 11 Stratum C participants who had metastatic tumors.
Overall Number of Participants Analyzed 40
Mean (Standard Error)
Unit of Measure: min(-1)
Poor Response 0.0775  (0.0089)
Good Response 0.0491  (0.0053)
13.Secondary Outcome
Title P95 of Ktrans by Good and Poor Response
Hide Description The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%. P95 denotes the level of each kinetic parameter exceeding 95% of its values in each tumor.
Time Frame at week 10 after start of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Two Stratum A participants with no histologic response were excluded.
Arm/Group Title All Participants
Hide Arm/Group Description:
All 42 evaluable participants in this study had osteosarcoma. This analysis includes 29 Stratum A participants who had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis, and 11 Stratum C participants who had metastatic tumors.
Overall Number of Participants Analyzed 40
Mean (Standard Error)
Unit of Measure: min(-1)
Poor Response 0.2047  (0.0224)
Good Response 0.1228  (0.0136)
14.Secondary Outcome
Title Difference Between Good and Poor Response by SUVmax
Hide Description The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
Time Frame at week 10 after start of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
One participant with no histologic response but with evaluable imaging was excluded.
Arm/Group Title All Participants
Hide Arm/Group Description:
Thirty-two participants with osteosarcoma were evaluated in this study. The analysis for this outcome measure included 23 Stratum A participants who had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis, and 8 Stratum C participants who had metastatic tumors.
Overall Number of Participants Analyzed 31
Mean (Standard Error)
Unit of Measure: (unitless)
Poor Response 6.2894  (0.9303)
Good Response 3.2720  (0.3814)
15.Other Pre-specified Outcome
Title Number of Participants With Neuropathic Pain (NP) Following Surgery
Hide Description Of the 43 participants enrolled on this trial, 37 met criteria for evaluation of neuropathic pain (NP) following definitive surgery. The 37 participants underwent 38 surgeries: one participant had a limb-sparing surgery followed by an amputation surgery. Six of 43 participants were excluded from evaluation for NP: 1 due to deep vein thrombosis, 2 removed from study prior to surgery, 1 removed immediately after surgery to receive radiation therapy, 1 had non-extremity osteosarcoma, and 1 patient had a fibula resection. Patients were followed for neuropathic pain daily for the first week postoperatively and weekly for up to 6 months postoperatively.
Time Frame Up to 6 months postoperatively
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Amputation Group Limb Sparing Group Entire Study Group
Hide Arm/Group Description:
Participants had metastatic disease at diagnosis.
Participants had localized disease at diagnosis. One participant had 2 surgeries.
Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Overall Number of Participants Analyzed 11 26 37
Overall Number of Units Analyzed
Type of Units Analyzed: Number of Surgeries
11 27 38
Measure Type: Number
Unit of Measure: participants
10 20 30
16.Other Pre-specified Outcome
Title Median Duration of Neuropathic Pain
Hide Description Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain. Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame From surgery until resolution of NP symptoms, up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who met the criteria, had definitive surgery (either limb sparing or/and amputation), experienced neuropathic pain (NP) and were treated for NP until resolution of NP symptoms and off NP medications.
Arm/Group Title Amputation Group Limb Sparing Group Entire Study Group
Hide Arm/Group Description:
Participants had metastatic disease at diagnosis.
Participants had localized disease at diagnosis. One participant had 2 surgeries.
Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Overall Number of Participants Analyzed 10 20 30
Overall Number of Units Analyzed
Type of Units Analyzed: Number of Surgeries
10 21 31
Median (Full Range)
Unit of Measure: Weeks
3.5
(0.9 to 12.9)
4.9
(0.3 to 29.9)
4.4
(0.3 to 29.9)
17.Other Pre-specified Outcome
Title Mean Duration of Neuropathic Pain
Hide Description Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain (NP). Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame From surgery until resolution of NP symptoms, up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who met the criteria, had surgery, experienced neuropathic pain and were treated with NP medication.
Arm/Group Title Amputation Group Limb Sparing Group Entire Study Group
Hide Arm/Group Description:
Participants had metastatic disease at diagnosis.
Participants had localized disease at diagnosis. One participant had 2 surgeries.
Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Overall Number of Participants Analyzed 10 20 30
Overall Number of Units Analyzed
Type of Units Analyzed: Number of Surgeries
10 21 31
Mean (Standard Deviation)
Unit of Measure: Weeks
4.9  (4.0) 7.2  (8.4) 6.5  (7.2)
18.Other Pre-specified Outcome
Title Median Duration of Neuropathic Pain Medication
Hide Description Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain (NP). Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame From surgery until resolution of NP symptoms, up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who met the criteria, had surgery, experienced neuropathic pain and were treated with NP medication.
Arm/Group Title Amputation Group Limb Sparing Group Entire Study Group
Hide Arm/Group Description:
Participants had metastatic disease at diagnosis.
Participants had localized disease at diagnosis. One participant had 2 surgeries.
Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Overall Number of Participants Analyzed 10 16 26
Overall Number of Units Analyzed
Type of Units Analyzed: Number of Surgeries
10 17 27
Median (Full Range)
Unit of Measure: Weeks
6.5
(3.0 to 30.0)
7.0
(1.7 to 29.9)
7.0
(1.7 to 30.0)
19.Other Pre-specified Outcome
Title Mean Duration of Neuropathic Pain Medication
Hide Description Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain. Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame From surgery until resolution of NP symptoms, up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Amputation Group Limb Sparing Group Entire Study Group
Hide Arm/Group Description:
Participants had metastatic disease at diagnosis.
Participants had localized disease at diagnosis. One participant had 2 surgeries.
Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Overall Number of Participants Analyzed 10 16 26
Overall Number of Units Analyzed
Type of Units Analyzed: Number of Surgeries
10 17 27
Mean (Standard Deviation)
Unit of Measure: Weeks
9.0  (8.0) 9.8  (8.4) 9.5  (8.1)
Time Frame Adverse events were recorded from on-study date through April 2015.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title A: Localized Resectable Disease C: Metastatic Tumors
Hide Arm/Group Description Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis. Stratum C participants had metastatic tumors.
All-Cause Mortality
A: Localized Resectable Disease C: Metastatic Tumors
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
A: Localized Resectable Disease C: Metastatic Tumors
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/31 (9.68%)      0/11 (0.00%)    
Cardiac disorders     
Hypotension * 1  1/31 (3.23%)  1 0/11 (0.00%)  0
General disorders     
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) * 1  1/31 (3.23%)  1 0/11 (0.00%)  0
Infections and infestations     
Infection with normal ANC or Grade 1 or 2 neutrophils, Lung (pneumonia) * 1  1/31 (3.23%)  1 0/11 (0.00%)  0
Nervous system disorders     
Cognitive disturbance * 1  1/31 (3.23%)  1 0/11 (0.00%)  0
Encephalopathy * 1  1/31 (3.23%)  1 0/11 (0.00%)  0
Neuropathy: motor * 1  1/31 (3.23%)  1 0/11 (0.00%) 
Neuropathy: sensory * 1  1/31 (3.23%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Hypoxia * 1  1/31 (3.23%)  1 0/11 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE v3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
A: Localized Resectable Disease C: Metastatic Tumors
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/31 (100.00%)      11/11 (100.00%)    
Blood and lymphatic system disorders     
Hemoglobin * 1  30/31 (96.77%)  255 11/11 (100.00%)  135
Leukocytes (total WBC) * 1  30/31 (96.77%)  230 11/11 (100.00%)  123
Platelets * 1  30/31 (96.77%)  212 11/11 (100.00%)  137
Lymphopenia * 1  6/31 (19.35%)  31 1/11 (9.09%)  5
Neutrophils/granulocytes (ANC/AGC) * 1  31/31 (100.00%)  241 11/11 (100.00%)  130
Cardiac disorders     
Hypertension * 1  12/31 (38.71%)  29 1/11 (9.09%)  1
Supraventricular and nodal arrhythmia, sinus tachycardia * 1  9/31 (29.03%)  14 2/11 (18.18%)  3
Prolonged QTc interval * 1  5/31 (16.13%)  7 1/11 (9.09%)  1
Hypotension * 1  3/31 (9.68%)  4 1/11 (9.09%)  1
Left ventricular systolic dysfunction * 1  8/31 (25.81%)  12 5/11 (45.45%)  7
Conduction abnormality/atrioventricular heart block, conduction abnormality, NOS * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Supraventricular and nodal arrhythmia, sinus arrhythmia * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Ear and labyrinth disorders     
Hearing: patients with/without baseline audiogram and enrolled in a monitoring program * 1  14/31 (45.16%)  19 6/11 (54.55%)  11
Tinnitus * 1  6/31 (19.35%)  8 1/11 (9.09%)  2
Eye disorders     
Vision-blurred vision * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Gastrointestinal disorders     
Mucositis/stomatitis (clinical exam), oral cavity * 1  25/31 (80.65%)  101 7/11 (63.64%)  39
Nausea * 1  24/31 (77.42%)  173 7/11 (63.64%)  65
Vomiting * 1  25/31 (80.65%)  148 8/11 (72.73%)  47
Anorexia * 1  22/31 (70.97%)  84 8/11 (72.73%)  30
Constipation * 1  12/31 (38.71%)  30 4/11 (36.36%)  10
Diarrhea * 1  13/31 (41.94%)  31 3/11 (27.27%)  7
Dehydration * 1  8/31 (25.81%)  9 3/11 (27.27%)  4
Hemorrhage, GI, rectum * 1  4/31 (12.90%)  4 3/11 (27.27%)  5
Mucositis/stomatitis (functional/symptomatic), oral cavity * 1  7/31 (22.58%)  11 6/11 (54.55%)  9
Heartburn/dyspepsia * 1  4/31 (12.90%)  6 0/11 (0.00%)  0
Hemorrhage, GI, lower GI NOS * 1  4/31 (12.90%)  6 0/11 (0.00%)  0
Esophagitis * 1  4/31 (12.90%)  6 1/11 (9.09%)  1
Hemorrhage, GI, upper GI NOS * 1  4/31 (12.90%)  4 1/11 (9.09%)  1
Mucositis/stomatitis (functional/symptomatic), esophagus * 1  4/31 (12.90%)  4 2/11 (18.18%)  2
Mucositis/stomatitis (clinical exam), anus * 1  3/31 (9.68%)  5 0/11 (0.00%)  0
Hemorrhage, GI, anus * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Hemorrhage, GI, oral cavity * 1  2/31 (6.45%)  4 2/11 (18.18%)  2
Mucositis/stomatitis (clinical exam), esophagus * 1  2/31 (6.45%)  2 1/11 (9.09%)  1
Mucositis/stomatitis (clinical exam), rectum * 1  2/31 (6.45%)  2 1/11 (9.09%)  1
Taste alteration (dysgeusia) * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Mucositis/stomatitis (functional/symptomatic), pharynx * 1  1/31 (3.23%)  1 1/11 (9.09%)  1
Proctitis * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
General disorders     
Pain, Abdomen NOS * 1  15/31 (48.39%)  43 4/11 (36.36%)  9
Weight loss * 1  19/31 (61.29%)  112 7/11 (63.64%)  36
Pain, Head/headache * 1  16/31 (51.61%)  45 6/11 (54.55%)  9
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) * 1  14/31 (45.16%)  43 2/11 (18.18%)  3
Pain, extremity-limb * 1  4/31 (12.90%)  6 0/11 (0.00%)  0
Fatigue (asthenia, lethargy, malaise) * 1  13/31 (41.94%)  40 4/11 (36.36%)  17
Pain, oral cavity * 1  14/31 (45.16%)  28 6/11 (54.55%)  13
Pain, throat/pharynx/larynx * 1  12/31 (38.71%)  28 5/11 (45.45%)  11
Pain, Back * 1  3/31 (9.68%)  3 0/11 (0.00%)  0
Pain, chest/thorax NOS * 1  4/31 (12.90%)  7 0/11 (0.00%)  0
Pain, esophagus * 1  5/31 (16.13%)  14 2/11 (18.18%)  2
Pain, urethra * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Pain, joint * 1  2/31 (6.45%)  4 0/11 (0.00%)  0
Pain, phantom (pain associated with missing limb) * 1  2/31 (6.45%)  2 1/11 (9.09%)  1
Pain, rectum * 1  3/31 (9.68%)  6 2/11 (18.18%)  3
Pain, stomach * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Pain, pain NOS * 1  3/31 (9.68%)  6 1/11 (9.09%)  1
Rigors/chills * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Pain, pleura * 1  2/31 (6.45%)  5 0/11 (0.00%)  0
Bone age (alteration in bone age) * 1  1/31 (3.23%)  1 1/11 (9.09%)  1
Pain, anus * 1  1/31 (3.23%)  1 1/11 (9.09%)  1
Hemorrhage/bleeding - other * 1  1/31 (3.23%)  1 2/11 (18.18%)  2
Pain, lip * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Immune system disorders     
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) * 1  6/31 (19.35%)  8 2/11 (18.18%)  2
Allergic reaction/hypersensitivity (including drug fever) * 1  5/31 (16.13%)  6 1/11 (9.09%)  1
Infections and infestations     
Febrile neutropenia * 1 [1]  20/31 (64.52%)  34 8/11 (72.73%)  18
Infection with normal ANC or Grade 1 or 2 neutrophils, skin (cellulitis) * 1  3/31 (9.68%)  3 0/11 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, catheter-related * 1  3/31 (9.68%)  4 1/11 (9.09%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils, blood * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), skin (cellulitis) * 1 [2]  2/31 (6.45%)  2 1/11 (9.09%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, oral cavity-gums (gingivitis) * 1  3/31 (9.68%)  6 2/11 (18.18%)  4
Colitis, infectious (e.g., Clostridium difficile) * 1  2/31 (6.45%)  3 0/11 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, wound * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), blood * 1 [3]  2/31 (6.45%)  2 1/11 (9.09%)  1
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), oral cavity-gums * 1 [3]  2/31 (6.45%)  3 2/11 (18.18%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils, mucosa * 1  2/31 (6.45%)  2 3/11 (27.27%)  3
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), catheter-related * 1 [3]  2/31 (6.45%)  2 5/11 (45.45%)  7
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), lung (pneumonia) * 1 [3]  1/31 (3.23%)  1 1/11 (9.09%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, bladder (urinary) * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, urinary tract NOS * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), conjunctiva * 1 [4]  0/31 (0.00%)  0 1/11 (9.09%)  1
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), eye NOS * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), mucosa * 1 [3]  0/31 (0.00%)  0 1/11 (9.09%)  1
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), urinary tract NOS * 1 [3]  0/31 (0.00%)  0 1/11 (9.09%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, lung (pneumonia) * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Infection (ANC <1.0 x 10e9/L, fever >38.5 degrees C.), blood * 1 [3]  0/31 (0.00%)  0 2/11 (18.18%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils, colon * 1  0/31 (0.00%)  0 2/11 (18.18%)  3
Metabolism and nutrition disorders     
ALT, SGPT (serum glutamic pyruvic transaminase) * 1  29/31 (93.55%)  291 10/11 (90.91%)  90
Albumin, serum-low (hypoalbuminemia) * 1  29/31 (93.55%)  258 10/11 (90.91%)  90
AST, SGOT (serum glutamic oxaloacetic transaminase) * 1  29/31 (93.55%)  296 10/11 (90.91%)  91
Glucose, serum-high (hyperglycemia) * 1  13/31 (41.94%)  75 5/11 (45.45%)  21
Phosphate, serum-low (hypophosphatemia) * 1  26/31 (83.87%)  144 9/11 (81.82%)  71
Sodium, serum-low (hyponatremia) * 1  23/31 (74.19%)  128 6/11 (54.55%)  43
Proteinuria * 1  20/31 (64.52%)  69 11/11 (100.00%)  42
Potassium, serum-low (hypokalemia) * 1  21/31 (67.74%)  146 10/11 (90.91%)  73
Calcium, serum-low (hypocalcemia) * 1  20/31 (64.52%)  80 7/11 (63.64%)  20
Bilirubin (hyperbilirubinemia) * 1  18/31 (58.06%)  98 6/11 (54.55%)  17
Magnesium, serum-low (hypomagnesemia) * 1  16/31 (51.61%)  105 6/11 (54.55%)  34
Uric acid, serum-high (hyperuricemia) * 1  8/31 (25.81%)  19 1/11 (9.09%)  1
Glucose, serum-low (hypoglycemia) * 1  2/31 (6.45%)  2 1/11 (9.09%)  2
Hemoglobinuria * 1  7/31 (22.58%)  8 0/11 (0.00%)  0
Potassium, serum-high (hyperkalemia) * 1  3/31 (9.68%)  4 1/11 (9.09%)  1
Bicarbonate, serum-low * 1  8/31 (25.81%)  24 4/11 (36.36%)  8
Magnesium, serum-high (hypermagnesemia) * 1  7/31 (22.58%)  13 2/11 (18.18%)  3
GGT (gamma-glutamyl transpeptidase) * 1  5/31 (16.13%)  24 4/11 (36.36%)  14
Sodium, serum-high (hypernatremia) * 1  4/31 (12.90%)  4 1/11 (9.09%)  1
Creatinine * 1  6/31 (19.35%)  11 4/11 (36.36%)  6
Calcium, serum-high (hypercalcemia) * 1  3/31 (9.68%)  3 0/11 (0.00%)  0
Alkaline phosphatase * 1  5/31 (16.13%)  14 3/11 (27.27%)  4
Glomerular filtration rate * 1  4/31 (12.90%)  4 2/11 (18.18%)  2
Musculoskeletal and connective tissue disorders     
Fracture * 1  2/31 (6.45%)  3 1/11 (9.09%)  1
Joint-effusion * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Nervous system disorders     
Dizziness * 1  5/31 (16.13%)  5 3/11 (27.27%)  4
Neuropathy: sensory * 1  3/31 (9.68%)  4 0/11 (0.00%)  0
Encephalopathy * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Somnolence/depressed level of consciousness * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
Neuropathy: motor * 1  1/31 (3.23%)  1 2/11 (18.18%)  2
Psychiatric disorders     
Confusion * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Renal and urinary disorders     
Urinary retention (including neurogenic bladder) * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Hemorrhage, GU, bladder * 1  3/31 (9.68%)  5 2/11 (18.18%)  2
Hemorrhage, GU, urinary NOS * 1  3/31 (9.68%)  3 1/11 (9.09%)  1
Urinary electrolyte wasting (e.g., Fanconi's syndrome, renal tubular acidosis) * 1  3/31 (9.68%)  3 5/11 (45.45%)  7
Reproductive system and breast disorders     
Irregular menses (change from baseline) * 1  3/31 (9.68%)  4 1/11 (9.09%)  2
Respiratory, thoracic and mediastinal disorders     
Hemorrhage, pulmonary/upper respiratory, Nose * 1  23/31 (74.19%)  106 9/11 (81.82%)  38
Cough * 1  3/31 (9.68%)  3 0/11 (0.00%)  0
Pulmonary/upper respiratory - other * 1  2/31 (6.45%)  2 0/11 (0.00%)  0
Hemorrhage, pulmonary/upper respiratory, bronchopulmonary NOS * 1  1/31 (3.23%)  1 1/11 (9.09%)  1
Skin and subcutaneous tissue disorders     
Rash/desquamation * 1  12/31 (38.71%)  23 2/11 (18.18%)  2
Pruritus/itching * 1  5/31 (16.13%)  5 2/11 (18.18%)  3
Hair loss/alopecia (scalp or body) * 1  9/31 (29.03%)  11 3/11 (27.27%)  3
Skin breakdown/decubitus ulcer * 1  2/31 (6.45%)  3 0/11 (0.00%)  0
Chelitis * 1  4/31 (12.90%)  5 1/11 (9.09%)  1
Rash: hand-foot skin reaction * 1  1/31 (3.23%)  2 1/11 (9.09%)  1
Injection site reaction/extravasation changes * 1  0/31 (0.00%)  0 1/11 (9.09%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE v3.0
[1]
Fever of unknown origin without clinically or microbiologically documented infection) (ANC <1.0 x 10e9/L)
[2]
Documented clinically or microbiologically
[3]
Documented clinically or microbiologically.
[4]
Documented clinically or microbiologically)
Accrual to this study was stopped early after 4.5 years due to slow accrual of participants. No eligible participants were enrolled on Stratum B. All enrolled participants continue on study and results will be reported when available.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Michael Bishop, MD
Organization: St. Jude Children's Research Hospital
Phone: 866-278-5833
EMail: referralinfo@stjude.org
Layout table for additonal information
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00667342     History of Changes
Other Study ID Numbers: OS2008
GENENTECH PHARM ( Other Identifier: Genentech Pharmaceuticals )
NCI-2009-00846 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Submitted: April 24, 2008
First Posted: April 28, 2008
Results First Submitted: June 9, 2014
Results First Posted: August 4, 2014
Last Update Posted: June 28, 2019