Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00153920
• Collaborator: Beth Israel Deaconess Medical Center (Other), Massachusetts General Hospital (Other), Brigham and Women's Hospital (Other), Roswell Park Cancer Institute (Other), Emory University (Other), Memorial Sloan Kettering Cancer Center (Other), Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 66
• Locations: 6
• Arm: 1
• Duration (Months): 57
• Patients Per Site: 11
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Bortezomib (Velcade) has just recently been approved by the FDA for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. This study will determine if Velcade is effective in treating patients with multiple myeloma that have had no prior treatment for the disease. We will also use whole-genome scanning to identify drug response biomarkers in bone marrow samples as well as nerve fiber studies to compare nerves prior to the use of Velcade and after treatment with Velcade.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: bortezomib	Phase 2

Detailed Description

Primary Objective

• To evaluate the objective response rate (CR + PR) to bortezomib alone in patients with newly diagnosed multiple myeloma.

Secondary Objectives

• To evaluate the tolerability and toxicity.

• To evaluate time to progression.

• To assess the frequency and severity of peripheral neuropathy.

• To evaluate the impact of early intervention with dose modification and explore symptomatic treatment of peripheral neuropathy.

Exploratory Objectives

• To perform pharmacogenomic analysis of molecular markers associated with response or non-response.

Statistical Design A one stage design is used to evaluate ORR. With 60 evaluable participants, if at least 27 objective responses are observed then bortezomib will be considered promising. The probability of concluding the treatment promising is >0.95 with a true ORR of 55% and <0.07 with a true ORR of 35%.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Velcade (Bortezomib) in Patients With Previously Untreated Multiple Myeloma
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Jul 1, 2007
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bortezomib Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.	Drug: bortezomib; Other Names: Velcade

Outcome Measures

Primary Outcome Measures

1. Objective Response (OR) Rate [Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).]

   Objective response was defined as complete response (CR) or partial response (PR) according to European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). CR required all of the following: Negative immunofixation on the serum and urine at two consecutive times for minimum 6 weeks; Disappearance of soft tissue plasmacytomas for at least 6 weeks; <5% plasma cells in bone marrow on 2 determinations for a minimum of 6 weeks; No increase in the size or number of lytic bone lesions. PR required all the following: ≥50% reduction in the level of the serum monoclonal protein on 2 determinations for minimum 6 weeks; If present, reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg on 2 determinations for minimum 6 weeks; ≥50% reduction size of soft tissue plasmacytomas for minimum 6 weeks; No increase in the number or size of lytic bone lesions. Development of a compression fracture does not exclude response in either category.

Secondary Outcome Measures

1. Very Good Partial Response (VGPR) Rate [Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).]

   Very good partial response or better was defined per International Uniform Response criteria (Durie B, Harousseau JL, Miquel JS, et al Leukemia 2006). See CR requirements in primary outcome measure plus if serum and urine M protein were unmeasurable then immunoglobulin free light chain (FLC) must be in a normal ratio of 0.26-1.65 at two consecutive times. VGPR required the following: Serum and urine M-component detectable by immunofixation but not on electrophoresis; >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP); if the serum and urine M protein were unmeasurable then a >90% decrease in the difference between involved and uninvolved FLC levels.

2. Time to Progression (TTP) [Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months.]

   TTP based on the Kaplan-Meier method is defined as the time from start of treatment to documentation of disease progression (PD). Participants without evidence of PD were censored at the latest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing or new soft tissue plasmacytomas and/or lytic lesions; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).

3. Progression-Free Survival (PFS) [Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months as of the data analysis.]

   PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing soft tissue plasmacytomas and/or lytic lesions or new; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).

4. Number of Participants With Treatment-Emergent Sensory Neuropathy [Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).]

   Number of participants experiencing any grade treatment-emergent sensory neuropathy events based on CTCAEv3 as reported on case report forms.

5. Number of Participants With Treatment-Emergent Neuropathic Pain [Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).]

   Number of participants experiencing any grade treatment-emergent neuropathic pain events based on CTCAEv3 as reported on case report forms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of multiple myeloma based upon standard criteria

• Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of > 1 g/dl and/or urine monoclonal immunoglobulin spike of > 200mg/24 hours.

• Karnofsky performance status of > 60

• Hemoglobin > 8.0 g/dL

• AST (SGOT) < 3 x ULN

• ALT < 3 x ULN

• Total bilirubin < 2 x ULN

• Is infertile or is practicing an adequate form of contraception

• 18 years of age or older

Exclusion Criteria:

• Prior treatment with systemic chemotherapy

• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes

• Plasma cell leukemia

• Calculated or measured creatinine clearance < 30 mL/minute within 14 days of enrollment

• Grade 2 or greater peripheral neuropathy

• Hypersensitivity to bortezomib, boron or mannitol

• Severe hypercalcemia

• HIV positive

• Known active hepatitis B or C

• New York Hospital Association Class III or IV heart failure

• Second malignancy requiring concurrent treatment

• Other serious medical or psychiatric illness

• Pregnant women

• Dialysis dependent patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory Winship Cancer Institute	Atlanta	Georgia	United States	30322
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	Roswell Park Cancer Institute	Buffalo	New York	United States	04263
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Beth Israel Deaconess Medical Center
• Massachusetts General Hospital
• Brigham and Women's Hospital
• Roswell Park Cancer Institute
• Emory University
• Memorial Sloan Kettering Cancer Center
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Paul Richardson, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paul G. Richardson, MD, Principle Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00153920
• Other Study ID Numbers: 03-328
• First Posted: Sep 12, 2005
• Last Update Posted: Jun 11, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Paul G. Richardson, MD, Principle Investigator, Dana-Farber Cancer Institute: multiple myeloma; Velcade; bortezomib
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Bortezomib

Study Results

Participant Flow

Recruitment Details	66 participants were enrolled between December 2003 and September 2005.

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Period Title: Overall Study
STARTED	66
Eligible and Treated	64
COMPLETED	36
NOT COMPLETED	30

Baseline Characteristics

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Overall Participants	64
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	20 31.3%
Male	44 68.8%
Race/Ethnicity, Customized (participants) [Number]
White	59 92.2%
Non-White	5 7.8%
Region of Enrollment (participants) [Number]
United States	64 100%
ISS Stage (participants) [Number]
ISS Stage I	32 50%
ISS Stage II	26 40.6%
ISS Stage III	4 6.3%
Unknown	2 3.1%

Outcome Measures

1. Primary Outcome

Title	Objective Response (OR) Rate
Description	Objective response was defined as complete response (CR) or partial response (PR) according to European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). CR required all of the following: Negative immunofixation on the serum and urine at two consecutive times for minimum 6 weeks; Disappearance of soft tissue plasmacytomas for at least 6 weeks; <5% plasma cells in bone marrow on 2 determinations for a minimum of 6 weeks; No increase in the size or number of lytic bone lesions. PR required all the following: ≥50% reduction in the level of the serum monoclonal protein on 2 determinations for minimum 6 weeks; If present, reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg on 2 determinations for minimum 6 weeks; ≥50% reduction size of soft tissue plasmacytomas for minimum 6 weeks; No increase in the number or size of lytic bone lesions. Development of a compression fracture does not exclude response in either category.
Time Frame	Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of eligible and treated participants.

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Measure Participants	64
Number (95% Confidence Interval) [proportion of participants]	0.41 0.6%

2. Secondary Outcome

Title	Very Good Partial Response (VGPR) Rate
Description	Very good partial response or better was defined per International Uniform Response criteria (Durie B, Harousseau JL, Miquel JS, et al Leukemia 2006). See CR requirements in primary outcome measure plus if serum and urine M protein were unmeasurable then immunoglobulin free light chain (FLC) must be in a normal ratio of 0.26-1.65 at two consecutive times. VGPR required the following: Serum and urine M-component detectable by immunofixation but not on electrophoresis; >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP); if the serum and urine M protein were unmeasurable then a >90% decrease in the difference between involved and uninvolved FLC levels.
Time Frame	Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of eligible and treated participants.

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Measure Participants	64
Number (95% Confidence Interval) [proportion of participants]	.17 0.3%

3. Secondary Outcome

Title	Time to Progression (TTP)
Description	TTP based on the Kaplan-Meier method is defined as the time from start of treatment to documentation of disease progression (PD). Participants without evidence of PD were censored at the latest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing or new soft tissue plasmacytomas and/or lytic lesions; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).
Time Frame	Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of eligible and treated participants.

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Measure Participants	64
Median (95% Confidence Interval) [months]	17.3

4. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing soft tissue plasmacytomas and/or lytic lesions or new; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).
Time Frame	Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months as of the data analysis.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of eligible and treated participants.

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Measure Participants	64
Median (95% Confidence Interval) [months]	17.0

5. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Sensory Neuropathy
Description	Number of participants experiencing any grade treatment-emergent sensory neuropathy events based on CTCAEv3 as reported on case report forms.
Time Frame	Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of eligible and treated participants.

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Measure Participants	64
Number [participants]	41 64.1%

6. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Neuropathic Pain
Description	Number of participants experiencing any grade treatment-emergent neuropathic pain events based on CTCAEv3 as reported on case report forms.
Time Frame	Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of eligible and treated participants.

Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Measure Participants	64
Number [participants]	8 12.5%

Adverse Events

Time Frame	Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).
Adverse Event Reporting Description	Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with bortezomib treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with bortezomib treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Arm/Group Title	Bortezomib
Arm/Group Description	Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
All Cause Mortality
	Bortezomib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bortezomib
	Affected / at Risk (%)	# Events
Total	33/64 (51.6%)
Gastrointestinal disorders
Constipation	2/64 (3.1%)
Nausea	1/64 (1.6%)
General disorders
Fatigue	2/64 (3.1%)
Fever w/o neutropenia	1/64 (1.6%)
Edema limb	1/64 (1.6%)
Pain-other	1/64 (1.6%)
Infections and infestations
Infection-other	2/64 (3.1%)
Investigations
Leukocytes	4/64 (6.3%)
Lymphopenia	14/64 (21.9%)
Neutrophils	4/64 (6.3%)
Platelets	3/64 (4.7%)
Metabolism and nutrition disorders
Anorexia	1/64 (1.6%)
Dehydration	1/64 (1.6%)
Hypokalemia	1/64 (1.6%)
Hyponatremia	2/64 (3.1%)
Hyperuricemia	1/64 (1.6%)
Nervous system disorders
Neuropathy-motor	2/64 (3.1%)
Neuropathy-sensory	2/64 (3.1%)
Depressed level of consciousness	1/64 (1.6%)
Syncope	3/64 (4.7%)
Neuropathic, pain	3/64 (4.7%)
Psychiatric disorders
Anxiety	1/64 (1.6%)
Depression	1/64 (1.6%)
Renal and urinary disorders
Proteinuria	1/64 (1.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/64 (4.7%)
Skin and subcutaneous tissue disorders
Rash/desquamation	1/64 (1.6%)
Vascular disorders
Hypotension	3/64 (4.7%)
Other (Not Including Serious) Adverse Events
	Bortezomib
	Affected / at Risk (%)	# Events
Total	62/64 (96.9%)
Blood and lymphatic system disorders
Hemoglobin	4/64 (6.3%)
Hematologic-other	1/64 (1.6%)
Lymphatics-other	2/64 (3.1%)
Cardiac disorders
Sinus tachycardia	2/64 (3.1%)
Ear and labyrinth disorders
Tinnitus	2/64 (3.1%)
Eye disorders
Dry eye syndrome	3/64 (4.7%)
Double vision	1/64 (1.6%)
Vision-blurred	3/64 (4.7%)
Tearing	4/64 (6.3%)
Ocular-other	7/64 (10.9%)
Gastrointestinal disorders
Constipation	32/64 (50%)
Diarrhea w/o prior colostomy	20/64 (31.3%)
Distention/bloating, abdominal	1/64 (1.6%)
Dry mouth	1/64 (1.6%)
Flatulence	1/64 (1.6%)
Dyspepsia	4/64 (6.3%)
Muco/stomatitis by exam, oral cavity	1/64 (1.6%)
Nausea	33/64 (51.6%)
Vomiting	9/64 (14.1%)
GI-other	4/64 (6.3%)
Oral cavity, hemorrhage	1/64 (1.6%)
Abdomen, pain	1/64 (1.6%)
Stomach, pain	3/64 (4.7%)
General disorders
Fatigue	26/64 (40.6%)
Fever w/o neutropenia	6/64 (9.4%)
Rigors/chills	4/64 (6.3%)
Constitutional, other	3/64 (4.7%)
Edema head and neck	2/64 (3.1%)
Edema limb	6/64 (9.4%)
Pain-other	9/64 (14.1%)
Immune system disorders
Allergic reaction	2/64 (3.1%)
Allergy-other	1/64 (1.6%)
Infections and infestations
Infection w/ unk ANC upper airway NOS	1/64 (1.6%)
Infection Gr0-2 neut, eye NOS	1/64 (1.6%)
Infection Gr0-2 neut, skin	1/64 (1.6%)
Infection-other	2/64 (3.1%)
Investigations
Leukocytes	18/64 (28.1%)
Lymphopenia	7/64 (10.9%)
Neutrophils	8/64 (12.5%)
Platelets	25/64 (39.1%)
Weight gain	1/64 (1.6%)
Weight loss	7/64 (10.9%)
Alkaline phosphatase	1/64 (1.6%)
ALT, SGPT	3/64 (4.7%)
Amylase	2/64 (3.1%)
AST, SGOT	4/64 (6.3%)
Metabolism and nutrition disorders
Anorexia	10/64 (15.6%)
Dehydration	2/64 (3.1%)
Hypoalbuminemia	2/64 (3.1%)
Hypocalcemia	2/64 (3.1%)
Hyperglycemia	1/64 (1.6%)
Hypermagnesemia	2/64 (3.1%)
Hyperkalemia	1/64 (1.6%)
Hypokalemia	4/64 (6.3%)
Hypernatremia	2/64 (3.1%)
Hyponatremia	4/64 (6.3%)
Musculoskeletal and connective tissue disorders
Nonneuropathic lower extr muscle weak	2/64 (3.1%)
Nonneuropathic generalized weakness	4/64 (6.3%)
Musculoskeletal/soft tissue-other	11/64 (17.2%)
Chest wall, pain	1/64 (1.6%)
Extremity-limb, pain	6/64 (9.4%)
Joint, pain	3/64 (4.7%)
Muscle, pain	5/64 (7.8%)
Nervous system disorders
Tinnitus	1/64 (1.6%)
Encephalopathy	1/64 (1.6%)
Taste disturbance	2/64 (3.1%)
Ataxia	1/64 (1.6%)
Dizziness	8/64 (12.5%)
Neuropathy-motor	5/64 (7.8%)
Neuropathy-sensory	39/64 (60.9%)
Neurologic-other	3/64 (4.7%)
Head/headache	9/64 (14.1%)
Neuropathic, pain	5/64 (7.8%)
Psychiatric disorders
Insomnia	3/64 (4.7%)
Depression	1/64 (1.6%)
Renal and urinary disorders
Renal/GU-other	3/64 (4.7%)
Reproductive system and breast disorders
Breast, pain	1/64 (1.6%)
Pelvic, pain	1/64 (1.6%)
Testicle, pain	4/64 (6.3%)
Uterus, pain	1/64 (1.6%)
Erectile impotence	1/64 (1.6%)
Sexual/Reproductive function-Other	2/64 (3.1%)
Respiratory, thoracic and mediastinal disorders
Nose, hemorrhage	1/64 (1.6%)
Cough	2/64 (3.1%)
Dyspnea	3/64 (4.7%)
Skin and subcutaneous tissue disorders
Sweating	2/64 (3.1%)
Pruritus/itching	1/64 (1.6%)
Rash/desquamation	15/64 (23.4%)
Skin-other	4/64 (6.3%)
Vascular disorders
Hypotension	4/64 (6.3%)
Hot flashes	1/64 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.