Trial Outcomes & Findings for A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma (NCT NCT00667342)

Last Updated: 2023-08-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

After all patients have completed therapy, up to 1 year after last patient is enrolled

Results posted on

2023-08-07

Participant Flow

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

All participants had newly diagnosed high-grade, biopsy-proven osteosarcoma, or malignant fibrous histiocytoma (MFH) of bone

Participant milestones

Participant milestones
Measure	A: Localized Resectable Disease Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.
Overall Study STARTED	31	12
Overall Study COMPLETED	17	3
Overall Study NOT COMPLETED	14	9

Reasons for withdrawal

Reasons for withdrawal
Measure	A: Localized Resectable Disease Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Physician Decision	3	0
Overall Study Relapse or tumor progression	9	7
Overall Study Adverse Event	0	1
Overall Study Ineligible	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	B: Localized Unresectable Disease Participants with localized unresectable primary tumors were to participate in Stratum B. No participants were enrolled to this stratum.	C: Metastatic Tumors n=12 Participants Stratum C participants had metastatic tumors.	Total n=43 Participants Total of all reporting groups
Age, Continuous	12 years n=5 Participants	—	12 years n=5 Participants	12 years n=4 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	—	5 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	—	7 Participants n=5 Participants	23 Participants n=4 Participants

PRIMARY outcome

Timeframe: After all patients have completed therapy, up to 1 year after last patient is enrolled

Population: 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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=11 Participants Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Number of Participants With Unacceptable Toxicity Grade 2, 3 or 4 Major Wound Complication	7 participants	2 participants	—
Number of Participants With Unacceptable Toxicity Grade 4 Hypertension	0 participants	0 participants	—
Number of Participants With Unacceptable Toxicity Grade 4 Proteinuria	0 participants	0 participants	—
Number of Participants With Unacceptable Toxicity Grade 4 Bleeding	0 participants	0 participants	—
Number of Participants With Unacceptable Toxicity Grade 3/4 Thrombosis/Embolism	1 participants	0 participants	—

PRIMARY outcome

Timeframe: After all patients have completed therapy, up to 4 years after last patient is enrolled

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
3-Year Event Free Survival	0.575 Probability Interval 0.402 to 0.747	—	—

SECONDARY outcome

Timeframe: After 6 cycles of chemotherapy, up to 1 year after the start of therapy

Population: All Stratum A participants were evaluated. The tumor sample for analysis was not obtained for one of the 12 Stratum C participants.

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=11 Participants Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Histologic Response by Stratum Grade I	1 participants	0 participants	—
Histologic Response by Stratum Grade IIA	5 participants	1 participants	—
Histologic Response by Stratum Grade IIB	17 participants	7 participants	—
Histologic Response by Stratum Grade III	8 participants	3 participants	—

SECONDARY outcome

Timeframe: After all patients have completed therapy, up to 2 years after last patient is enrolled

Population: All the 42 evaluable participants were included in this analysis.

Kaplan-Meier method was used to estimate the EFS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=42 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
2-Year Event Free Survival (EFS) of Patients With Osteosarcoma	0.617 probability Interval 0.47 to 0.764	—	—

SECONDARY outcome

Timeframe: After all patients have completed therapy, up to 2 years after last patient is enrolled

Population: All the 42 evaluable participants in this study had osteosarcoma, of which 12 died and 20 were still alive as of 05/04/2015.

Kaplan-Meier method was used to estimate the OS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=42 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
2-Year Overall Survival (OS) of Patients With Osteosarcoma	0.880 probability Interval 0.782 to 0.978	—	—

SECONDARY outcome

Timeframe: After all patients have completed therapy, up to 2 years after last patient is enrolled

Population: OS2008 Localized Resectable Disease group had 31 participants: 14 had events, 17 had no events.

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
2-Year Event Free Survival (EFS) in Patients With Localized Resectable Disease Compared to St. Jude OS99 Protocol.	0.642 probability Interval 0.473 to 0.81	—	—

SECONDARY outcome

Timeframe: After all patients have completed therapy, up to 2 years after last patient is enrolled

Population: OS2008 Localized Resectable Disease group had 31 participants: 7 were expired and 24 still alive

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
2-Year Overall Survival (OS) in Patients With Localized Resectable Disease Compared to OS99 Protocol.	0.934 probability Interval 0.847 to 1.0	—	—

SECONDARY outcome

Timeframe: Baseline through Week 10

Population: The number analyzed at each time point differed due to missing observations at some of the time points

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=11 Participants Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Mean Ktrans Baseline	0.13 min(-1) Standard Deviation 0.04	0.15 min(-1) Standard Deviation 0.07	—
Mean Ktrans Day -2	0.11 min(-1) Standard Deviation 0.05	0.14 min(-1) Standard Deviation 0.03	—
Mean Ktrans Day 1	0.12 min(-1) Standard Deviation 0.06	0.16 min(-1) Standard Deviation 0.04	—
Mean Ktrans Day 5	0.14 min(-1) Standard Deviation 0.06	0.16 min(-1) Standard Deviation 0.04	—
Mean Ktrans Week 5	0.08 min(-1) Standard Deviation 0.04	0.10 min(-1) Standard Deviation 0.05	—
Mean Ktrans Week 10	0.07 min(-1) Standard Deviation 0.05	0.07 min(-1) Standard Deviation 0.03	—

SECONDARY outcome

Timeframe: Baseline through Week 10

Population: The number analyzed at each time point differed due to missing observations at some of the time points

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=11 Participants Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Mean Vp Baseline	0.0081 (unitless) Standard Deviation 0.0024	0.0094 (unitless) Standard Deviation 0.0016	—
Mean Vp Day -2	0.0067 (unitless) Standard Deviation 0.0020	0.0077 (unitless) Standard Deviation 0.0022	—
Mean Vp Day 1	0.0070 (unitless) Standard Deviation 0.0027	0.0095 (unitless) Standard Deviation 0.0027	—
Mean Vp Day 5	0.0066 (unitless) Standard Deviation 0.0033	0.0089 (unitless) Standard Deviation 0.0029	—
Mean Vp Week 5	0.0063 (unitless) Standard Deviation 0.0029	0.0069 (unitless) Standard Deviation 0.0032	—
Mean Vp Week 10	0.0060 (unitless) Standard Deviation 0.0044	0.0055 (unitless) Standard Deviation 0.0026	—

SECONDARY outcome

Timeframe: Baseline through Week 10

Population: The number analyzed at each time point differed due to missing observations at some of the time points

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=11 Participants Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Mean Ve Week 10	0.2776 (unitless) Standard Deviation 0.1225	0.2726 (unitless) Standard Deviation 0.1596	—
Mean Ve Baseline	0.2543 (unitless) Standard Deviation 0.0785	0.2671 (unitless) Standard Deviation 0.0888	—
Mean Ve Day -2	0.2444 (unitless) Standard Deviation 0.0871	0.2623 (unitless) Standard Deviation 0.0781	—
Mean Ve Day 1	0.2564 (unitless) Standard Deviation 0.1209	0.2602 (unitless) Standard Deviation 0.0447	—
Mean Ve Day 5	0.2854 (unitless) Standard Deviation 0.1138	0.3126 (unitless) Standard Deviation 0.0727	—
Mean Ve Week 5	0.3055 (unitless) Standard Deviation 0.1622	0.3105 (unitless) Standard Deviation 0.1425	—

SECONDARY outcome

Timeframe: at week 10 after start of therapy

Population: Two Stratum A participants with no histologic response were excluded.

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%.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=40 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Histologic Response by Number of Participants Poor Response	22 Participants	—	—
Histologic Response by Number of Participants Good Response	18 Participants	—	—

SECONDARY outcome

Timeframe: at week 10 after start of therapy

Population: Two Stratum A participants with no histologic response were excluded.

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%.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=40 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Ktrans by Good and Poor Response Poor Response	0.0775 min(-1) Standard Error 0.0089	—	—
Ktrans by Good and Poor Response Good Response	0.0491 min(-1) Standard Error 0.0053	—	—

SECONDARY outcome

Timeframe: at week 10 after start of therapy

Population: Two Stratum A participants with no histologic response were excluded.

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=40 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
P95 of Ktrans by Good and Poor Response Poor Response	0.2047 min(-1) Standard Error 0.0224	—	—
P95 of Ktrans by Good and Poor Response Good Response	0.1228 min(-1) Standard Error 0.0136	—	—

SECONDARY outcome

Timeframe: at week 10 after start of therapy

Population: One participant with no histologic response but with evaluable imaging was excluded.

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%.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=31 Participants Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors Stratum C participants had metastatic tumors.	Entire Study Group Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Difference Between Good and Poor Response by SUVmax Poor Response	6.2894 (unitless) Standard Error 0.9303	—	—
Difference Between Good and Poor Response by SUVmax Good Response	3.2720 (unitless) Standard Error 0.3814	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 months postoperatively

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=11 Number of Surgeries Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=27 Number of Surgeries Stratum C participants had metastatic tumors.	Entire Study Group n=38 Number of Surgeries Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Number of Participants With Neuropathic Pain (NP) Following Surgery	10 participants	20 participants	30 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From surgery until resolution of NP symptoms, up to 6 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=10 Number of Surgeries Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=21 Number of Surgeries Stratum C participants had metastatic tumors.	Entire Study Group n=31 Number of Surgeries Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Median Duration of Neuropathic Pain	3.5 Weeks Interval 0.9 to 12.9	4.9 Weeks Interval 0.3 to 29.9	4.4 Weeks Interval 0.3 to 29.9

OTHER_PRE_SPECIFIED outcome

Timeframe: From surgery until resolution of NP symptoms, up to 6 months

Population: All participants who met the criteria, had surgery, experienced neuropathic pain and were treated with NP medication.

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.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=10 Number of Surgeries Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=21 Number of Surgeries Stratum C participants had metastatic tumors.	Entire Study Group n=31 Number of Surgeries Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Mean Duration of Neuropathic Pain	4.9 Weeks Standard Deviation 4.0	7.2 Weeks Standard Deviation 8.4	6.5 Weeks Standard Deviation 7.2

OTHER_PRE_SPECIFIED outcome

Timeframe: From surgery until resolution of NP symptoms, up to 6 months

Population: All participants who met the criteria, had surgery, experienced neuropathic pain and were treated with NP medication.

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=10 Number of Surgeries Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=17 Number of Surgeries Stratum C participants had metastatic tumors.	Entire Study Group n=27 Number of Surgeries Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Median Duration of Neuropathic Pain Medication	6.5 Weeks Interval 3.0 to 30.0	7.0 Weeks Interval 1.7 to 29.9	7.0 Weeks Interval 1.7 to 30.0

OTHER_PRE_SPECIFIED outcome

Timeframe: From surgery until resolution of NP symptoms, up to 6 months

Outcome measures

Outcome measures
Measure	A: Localized Resectable Disease n=10 Number of Surgeries Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=17 Number of Surgeries Stratum C participants had metastatic tumors.	Entire Study Group n=27 Number of Surgeries Participants enrolled on the study who met the criteria for evaluation of neuropathic pain.
Mean Duration of Neuropathic Pain Medication	9.0 Weeks Standard Deviation 8.0	9.8 Weeks Standard Deviation 8.4	9.5 Weeks Standard Deviation 8.1

Adverse Events

A: Localized Resectable Disease

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

C: Metastatic Tumors

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	A: Localized Resectable Disease n=31 participants at risk Stratum A participants had primary tumors potentially resectable by aggressive surgery, such as limb-salvage surgery or amputation, and no evidence of metastasis.	C: Metastatic Tumors n=11 participants at risk Stratum C participants had metastatic tumors.
Cardiac disorders Hypotension	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, Lung (pneumonia)	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.
Nervous system disorders Cognitive disturbance	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.
Nervous system disorders Encephalopathy	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.
Nervous system disorders Neuropathy: motor	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.
Nervous system disorders Neuropathy: sensory	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.2% 1/31 • Number of events 1 • Adverse events were recorded from on-study date through April 2015.	0.00% 0/11 • Adverse events were recorded from on-study date through April 2015.

Other adverse events

Additional Information

Michael Bishop, MD

St. Jude Children's Research Hospital

Phone: 866-278-5833

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place