Alternative Schedule of Velcade/Dexamethasone Plus Doxil for Patients With Multiple Myeloma

• Sponsor: Accelerated Community Oncology Research Network (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00366106
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 32
• Locations: 15
• Duration (Months): 56
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The current study is being conducted to evaluate the possibility that a different schedule of bortezomib, doxorubicin HCl liposome, and dexamethasone might decrease the incidence of peripheral neuropathy yet maintain similar efficacy and allow maintenance of bortezomib dosing for a longer period.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: bortezomib; Drug: dexamethasone; Drug: doxorubicin HCl liposome	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open Label Study Evaluating an Alternative Schedule of Velcade/Dexamethasone Plus Doxil in the Treatment of Multiple Myeloma
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Outcome Measures

Primary Outcome Measures

1. Incidence of Treatment-emergent Peripheral Neuropathy [Every 4 weeks from start of treatment until end of treatment]

Secondary Outcome Measures

1. Time to Progression (TTP) [TTP was measured from day 1 of treatment until time of progression, assessed up to 40 months]

2. Number of Participants With Treatment Response [Every 8 weeks from start of treatment until end of treatment]

   Complete Response (CR), Partial Response (PR), and Minor Response (MR) each required stable bone disease and normal calcium levels. CR also required 100% serum protein electrophoresis (SPEP) reduction, negative immunofixation (IF), 100% urine protein electrophoresis (UPEP)reduction, and <5% plasma cells in bone marrow. PR also required >=50% SPEP reduction, >=90% UPEP reduction, and >=50% reduction in plasma cells in bone marrow. MR also required >=25% SPEP reduction, >=50% UPEP reduction, and > 25% reduction in plasma cells.

3. Relative Dose Intensity of Bortezomib [Each dose of bortezomib (days 1, 4, 15, and 18 every 28 days)]

   Relative dose intensity is defined as actual dose/scheduled dose. Bortezomib is administered on Days 1, 4, 15, and 18 every 28 days.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient is at least 18 years of age.

• Patient has confirmed diagnosis of relapsed/refractory multiple myeloma with measurable disease by serum or urine. Measurable disease defined as monoclonal protein of ≥ 1g/dl on serum protein electrophoresis (SPEP) or > 200 mg urine M protein/ 24 hours

• Patient has received at least 1 prior treatment regimen. (Prior treatment with bortezomib is allowed.)

• Patient has ECOG ≤ 2

• Patient provides voluntary written informed consent before performance of any study-relates procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

• Patients who have received prior high dose chemotherapy with stem cell support are eligible for this study.

• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.

• Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

• Patient has a platelet count of < 50, 000 cells/mm³, within 14 days before enrollment.

• Patient has an absolute neutrophil count (ANC) ≤ 750/mm³ within 14 days before enrollment.

• Patient has a calculated or measured creatinine clearance of < 20 mL/min within 14 days before enrollment and/or serum creatinine ≥ 2.5 mg/dl.

• Patient has hemoglobin < 7.5 g/dl.

• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.

• Myocardial infarction within 6 months prior to enrollment or has (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.

• Patient has received a total cumulative dosage of anthracyclines exceeding 550 mg/m2.

• Patient has hypersensitivity to boron or mannitol.

• Patient has history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or the components of DOXIL.

• Patient has clinically significant coexisting illness unrelated to myeloma.

• Patient has uncontrolled diabetes.

• Patient has plasma cell leukemia.

• Patient has serum bilirubin > 1.5 x upper normal limit, alanine aminotransaminase (ALT), aspartate aminotransferase (AST) > 2.5 x upper normal limit (ULN), or alkaline phosphatase > 2.5 x ULN.

• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG)pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

• Patient has received other investigational drugs within 14 days before enrollment.

• Patient has serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wilshire Oncology Medical Group, Inc.	La Verne	California	United States	91750
2	Medical Oncology & Hematology	Waterbury	Connecticut	United States	06708
3	Advanced Medical Specialties	Miami	Florida	United States	33176
4	Northeast Georgia Cancer Care	Athens	Georgia	United States	30607
5	Augusta Oncology Associates, PC	Augusta	Georgia	United States	30901
6	Northwest Georgia Oncology Centers, PC	Marietta	Georgia	United States	30060
7	North Idaho Cancer Center	Coeur d'Alene	Idaho	United States	83814
8	Oncology-Hematology Associates, P.A.	Clinton	Maryland	United States	20735
9	Hematology Oncology Centers of the Northern Rockies, PC	Billings	Montana	United States	59101
10	Arena Oncology Associates	Lake Success	New York	United States	11042
11	Tri-County Hematology and Oncology Associates	Canton	Ohio	United States	44718
12	Mid Ohio Oncology/Hematology, Inc.	Columbus	Ohio	United States	43215
13	Lancaster Cancer Center, Ltd.	Lancaster	Pennsylvania	United States	17605
14	The West Clinic	Memphis	Tennessee	United States	38120
15	Cancer Specialists of Tidewater, Ltd.	Chesapeake	Virginia	United States	23320

Sponsors and Collaborators

• Accelerated Community Oncology Research Network
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Johnetta Blakely, MD, Accelerared Community Oncology Research Network, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Accelerated Community Oncology Research Network
• ClinicalTrials.gov Identifier: NCT00366106
• Other Study ID Numbers: ACORN ALJBMM0502
• First Posted: Aug 18, 2006
• Last Update Posted: Apr 6, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by Accelerated Community Oncology Research Network: Relapsed Multiple Myeloma; Refractory Multiple Myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Doxorubicin; Liposomal doxorubicin; Bortezomib

Study Results

Participant Flow

Recruitment Details	15 community oncology research sites across the US within the ACORN network participated in this study. Enrollment started in July 2006 but was stopped in December 2008 at the point when it became clear that enrollment was too slow to complete the planned enrollment target of 45 patients within the time frame allowed.
Pre-assignment Detail	Informed consent was obtained from all subjects. All subjects underwent screening procedures to verify eligibility.

Arm/Group Title	Treatment Group
Arm/Group Description	All subjects received bortezomib 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days and dexamethasone 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days. Following US FDA approval of doxorubicin HCl liposome injection in combination with bortezomib in May 2007, the study was amended to allow combination treatment with both bortezomib and doxorubicin HCl liposome injection 30 mg/m^2 on Day 4 every 28 days with dexamethasone. The target goal was 8 cycles of treatment.
Period Title: Overall Study
STARTED	32
COMPLETED	32
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment Group
Arm/Group Description	All subjects received bortezomib 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days and dexamethasone 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days. Following US FDA approval of doxorubicin HCl liposome injection in combination with bortezomib in May 2007, the study was amended to allow combination treatment with both bortezomib and doxorubicin HCl liposome injection 30 mg/m^2 on Day 4 every 28 days with dexamethasone. The target goal was 8 cycles of treatment.
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 43.8%
>=65 years	18 56.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (10.05)
Sex: Female, Male (Count of Participants)
Female	15 46.9%
Male	17 53.1%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Treatment-emergent Peripheral Neuropathy
Time Frame	Every 4 weeks from start of treatment until end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group
Arm/Group Description	All subjects received bortezomib 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days and dexamethasone 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days. Following US FDA approval of doxorubicin HCl liposome injection in combination with bortezomib in May 2007, the study was amended to allow combination treatment with both bortezomib and doxorubicin HCl liposome injection 30 mg/m^2 on Day 4 every 28 days with dexamethasone. The target goal was 8 cycles of treatment.
Measure Participants	32
Number [Participants]	11 34.4%

2. Secondary Outcome

Title	Time to Progression (TTP)
Time Frame	TTP was measured from day 1 of treatment until time of progression, assessed up to 40 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group
Arm/Group Description	All subjects received bortezomib 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days and dexamethasone 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days. Following US FDA approval of doxorubicin HCl liposome injection in combination with bortezomib in May 2007, the study was amended to allow combination treatment with both bortezomib and doxorubicin HCl liposome injection 30 mg/m^2 on Day 4 every 28 days with dexamethasone. The target goal was 8 cycles of treatment.
Measure Participants	32
Mean (Standard Deviation) [Months]	23.07 (3.20)

3. Secondary Outcome

Title	Number of Participants With Treatment Response
Description	Complete Response (CR), Partial Response (PR), and Minor Response (MR) each required stable bone disease and normal calcium levels. CR also required 100% serum protein electrophoresis (SPEP) reduction, negative immunofixation (IF), 100% urine protein electrophoresis (UPEP)reduction, and <5% plasma cells in bone marrow. PR also required >=50% SPEP reduction, >=90% UPEP reduction, and >=50% reduction in plasma cells in bone marrow. MR also required >=25% SPEP reduction, >=50% UPEP reduction, and > 25% reduction in plasma cells.
Time Frame	Every 8 weeks from start of treatment until end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group
Arm/Group Description	All subjects received bortezomib 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days and dexamethasone 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days. Following US FDA approval of doxorubicin HCl liposome injection in combination with bortezomib in May 2007, the study was amended to allow combination treatment with both bortezomib and doxorubicin HCl liposome injection 30 mg/m^2 on Day 4 every 28 days with dexamethasone. The target goal was 8 cycles of treatment.
Measure Participants	32
Number [Participants]	NA NaN

4. Secondary Outcome

Title	Relative Dose Intensity of Bortezomib
Description	Relative dose intensity is defined as actual dose/scheduled dose. Bortezomib is administered on Days 1, 4, 15, and 18 every 28 days.
Time Frame	Each dose of bortezomib (days 1, 4, 15, and 18 every 28 days)

Outcome Measure Data

Analysis Population Description

Note that the sample sized varied at each dose and ranged from 32 patients to 1 patient.

Arm/Group Title	Treatment Group
Arm/Group Description	All subjects received bortezomib 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days and dexamethasone 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days. Following US FDA approval of doxorubicin HCl liposome injection in combination with bortezomib in May 2007, the study was amended to allow combination treatment with both bortezomib and doxorubicin HCl liposome injection 30 mg/m^2 on Day 4 every 28 days with dexamethasone. The target goal was 8 cycles of treatment.
Measure Participants	32
Cycle 1 / Week 1	0.97 (0.158)
Cycle 1 / Week 1 Day 4	0.98 (0.159)
Cycle 1 / Week 3	0.97 (0.158)
Cycle 1 / Week 3 Day 18	0.97 (0.154)
Cycle 2 / Week 5	0.95 (0.144)
Cycle 2 / Week 5 Day 4	0.96 (0.148)
Cycle 2 / Week 7	0.95 (0.140)
Cycle 2 / Week 7 Day 18	0.96 (0.146)
Cycle 3 / Week 9	0.99 (0.147)
Cycle 3 / Week 9 Day 4	0.97 (0.121)
Cycle 3 / Week 11	0.97 (0.142)
Cycle 3 / Week 11 Day 18	0.95 (0.104)
Cycle 4 / Week 13	0.99 (0.152)
Cycle 4 / Week 13 Day 4	0.96 (0.111)
Cycle 4 / Week 15	0.99 (0.154)
Cycle 4 / Week 15 Day 18	0.96 (0.111)
Cycle 5 / Week 17	0.98 (0.151)
Cycle 5 / Week 17 Day 4	0.96 (0.110)
Cycle 5 / Week 19	1.00 (0.157)
Cycle 5 / Week 19 Day 18	0.97 (0.111)
Cycle 6 / Week 21	1.01 (0.162)
Cycle 6 / Week 21 Day 4	0.98 (0.114)
Cycle 6 / Week 23	1.01 (0.169)
Cycle 6 / Week 23 Day 18	0.99 (0.115)
Cycle 7 / Week 25	1.11 (0.154)
Cycle 7 / Week 25 Day 4	1.03 (0.148)
Cycle 7 / Week 27	1.08 (0.198)
Cycle 7 / Week 27 Day 18	1.03 (0.148)
Cycle 8 / Week 29	1.05 (0.213)
Cycle 8 / Week 29 Day 4	0.99 (0.140)
Cycle 8 / Week 31	1.05 (0.213)
Cycle 8 / Week 31 Day 18	1.04 (0.085)
Cycle 9 / Week 33	1.10 (0.488)
Cycle 9 / Week 33 Day 4	0.75 (NA)
Cycle 9 / Week 35	1.15 (0.417)
Cycle 10 / Week 37	1.22 (0.311)
Cycle 10 / Week 37 Day 4	1.00 (NA)
Cycle 10 / Week 39	1.22 (0.311)
Cycle 10 / Week 39 Day 18	1.00 (NA)
Cycle 11 / Week 41	1.22 (0.311)
Cycle 11 / Week 41 Day 4	1.00 (NA)
Cycle 11 / Week 43	1.44 (NA)
Cycle 11 / Week 43 Day 18	1.00 (NA)

Adverse Events

Time Frame	Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment.
Adverse Event Reporting Description	Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Arm/Group Title	Treatment Group
Arm/Group Description	All subjects received bortezomib 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days and dexamethasone 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days. Following US FDA approval of doxorubicin HCl liposome injection in combination with bortezomib in May 2007, the study was amended to allow combination treatment with both bortezomib and doxorubicin HCl liposome injection 30 mg/m^2 on Day 4 every 28 days with dexamethasone. The target goal was 8 cycles of treatment.
All Cause Mortality
	Treatment Group
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment Group
	Affected / at Risk (%)	# Events
Total	10/32 (31.3%)
Blood and lymphatic system disorders
Anemia	1/32 (3.1%)
Cardiac disorders
Atrial fibrillation	1/32 (3.1%)
Gastrointestinal disorders
Diarrhea	1/32 (3.1%)
Dysphagia	1/32 (3.1%)
General disorders
Fatigue	2/32 (6.3%)
Infections and infestations
Cellulitis	1/32 (3.1%)
Herpes zoster	1/32 (3.1%)
Pneumonia	2/32 (6.3%)
Sepsis	1/32 (3.1%)
Investigations
Aspartate aminotransferase increased	1/32 (3.1%)
Blood creatinine increased	1/32 (3.1%)
Metabolism and nutrition disorders
Dehydration	1/32 (3.1%)
Hypercalcemia	1/32 (3.1%)
Hyperglycemia	1/32 (3.1%)
Hyperglycemic hyperosmolar nonketotic syndrome	1/32 (3.1%)
Hypoglycemia	1/32 (3.1%)
Psychiatric disorders
Mental status changes	1/32 (3.1%)
Renal and urinary disorders
Renal failure	2/32 (6.3%)
Renal failure acute	1/32 (3.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/32 (3.1%)
Hypoxia	1/32 (3.1%)
Vascular disorders
Hypotension	1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	Treatment Group
	Affected / at Risk (%)	# Events
Total	28/32 (87.5%)
Blood and lymphatic system disorders
Anemia	5/32 (15.6%)
Febrile neutropenia	1/32 (3.1%)
Hemorrhagic diathesis	1/32 (3.1%)
Leukocytosis	1/32 (3.1%)
Neutropenia	3/32 (9.4%)
Thrombocytopenia	1/32 (3.1%)
Ear and labyrinth disorders
Ear pain	1/32 (3.1%)
Tinnitus	1/32 (3.1%)
Eye disorders
Eye discharge	1/32 (3.1%)
Eye irritation	1/32 (3.1%)
Lacrimation increased	1/32 (3.1%)
Ocular surface disease	1/32 (3.1%)
Vision blurred	1/32 (3.1%)
Visual impairment	1/32 (3.1%)
Gastrointestinal disorders
Abdominal pain lower	1/32 (3.1%)
Constipation	11/32 (34.4%)
Diarrhea	7/32 (21.9%)
Dry mouth	2/32 (6.3%)
Dyspepsia	1/32 (3.1%)
Flatulence	1/32 (3.1%)
Gastroesophageal reflux disease	1/32 (3.1%)
Glossodynia	1/32 (3.1%)
Nausea	8/32 (25%)
Oral pain	1/32 (3.1%)
Parotid gland enlargement	1/32 (3.1%)
Rectal hemorrhage	1/32 (3.1%)
Stomatitis	2/32 (6.3%)
Vomiting	7/32 (21.9%)
General disorders
Asthenia	2/32 (6.3%)
Chest pain	2/32 (6.3%)
Chills	1/32 (3.1%)
Face edema	1/32 (3.1%)
Facial pain	1/32 (3.1%)
Fatigue	9/32 (28.1%)
Lethargy	1/32 (3.1%)
Mucosal inflammation	1/32 (3.1%)
Edema peripheral	7/32 (21.9%)
Pain	1/32 (3.1%)
Pyrexia	3/32 (9.4%)
Infections and infestations
Abscess jaw	1/32 (3.1%)
Adenoviral upper respiratory infection	1/32 (3.1%)
Eye infection	1/32 (3.1%)
Herpes zoster	4/32 (12.5%)
Oral fungal infection	1/32 (3.1%)
Sinusitis	1/32 (3.1%)
Skin infection	1/32 (3.1%)
Upper respiratory tract infection	3/32 (9.4%)
Urinary tract infections	2/32 (6.3%)
Vulvovaginal mycotic infection	1/32 (3.1%)
Injury, poisoning and procedural complications
Arthropod bite	1/32 (3.1%)
Barotitis media	1/32 (3.1%)
Contusion	2/32 (6.3%)
Fall	1/32 (3.1%)
Vaginal laceration	1/32 (3.1%)
Investigations
Alanine aminotransferase increased	1/32 (3.1%)
Aspartate aminotransferase increased	1/32 (3.1%)
Blood alkaline phosphatase increased	1/32 (3.1%)
Blood creatine increased	1/32 (3.1%)
Blood creatinine increased	1/32 (3.1%)
Blood glucose increased	2/32 (6.3%)
Blood lactate dehydrogenase increased	1/32 (3.1%)
Blood potassium decreased	1/32 (3.1%)
Blood potassium increased	3/32 (9.4%)
Blood urea decreased	2/32 (6.3%)
Gamma-glutamyltransferase increased	1/32 (3.1%)
Hemoglobin decreased	2/32 (6.3%)
Heart rate increased	1/32 (3.1%)
Platelet count decreased	2/32 (6.3%)
Weight decreased	1/32 (3.1%)
Weight increased	2/32 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	3/32 (9.4%)
Dehydration	1/32 (3.1%)
Fluid retention	1/32 (3.1%)
Hyperglycemia	3/32 (9.4%)
Hyperkalemia	1/32 (3.1%)
Hypoalbuminemia	1/32 (3.1%)
Hypocalcemia	2/32 (6.3%)
Hypokalemia	2/32 (6.3%)
Hyponatremia	2/32 (6.3%)
Increased appetite	3/32 (9.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/32 (6.3%)
Back pain	3/32 (9.4%)
Flank pain	1/32 (3.1%)
Joint stiffness	1/32 (3.1%)
Joint swelling	1/32 (3.1%)
Muscle spasms	1/32 (3.1%)
Muscular weakness	3/32 (9.4%)
Musculoskeletal chest pain	2/32 (6.3%)
Musculoskeletal pain	3/32 (9.4%)
Myalgia	2/32 (6.3%)
Osteoarthritis	1/32 (3.1%)
Pain in extremity	3/32 (9.4%)
Nervous system disorders
Amnesia	1/32 (3.1%)
Burning feet syndrome	1/32 (3.1%)
Burning sensation	1/32 (3.1%)
Dizziness	2/32 (6.3%)
Dysgeusia	4/32 (12.5%)
Headache	3/32 (9.4%)
Hypoesthesia	2/32 (6.3%)
Migraine	1/32 (3.1%)
Neuralgia	1/32 (3.1%)
Neuropathy peripheral	11/32 (34.4%)
Paresthesia	5/32 (15.6%)
Parosmia	1/32 (3.1%)
Peripheral sensory neuropathy	2/32 (6.3%)
Syncope	2/32 (6.3%)
Psychiatric disorders
Anxiety	2/32 (6.3%)
Depression	2/32 (6.3%)
Insomnia	4/32 (12.5%)
Nervousness	1/32 (3.1%)
Renal and urinary disorders
Renal tubular acidosis	1/32 (3.1%)
Reproductive system and breast disorders
Erectile dysfunction	1/32 (3.1%)
Vaginal hemorrhage	1/32 (3.1%)
Vaginal mucosal blistering	1/32 (3.1%)
Vulvovaginal pruritis	2/32 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	7/32 (21.9%)
Dyspnea	4/32 (12.5%)
Epistaxis	1/32 (3.1%)
Hemoptysis	1/32 (3.1%)
Oropharyngeal blistering	1/32 (3.1%)
Oropharyngeal pain	2/32 (6.3%)
Postnasal drip	1/32 (3.1%)
Productive cough	1/32 (3.1%)
Rhinorrhea	2/32 (6.3%)
Sinus congestion	1/32 (3.1%)
Skin and subcutaneous tissue disorders
Alopecia	1/32 (3.1%)
Blister	1/32 (3.1%)
Hyperhidrosis	1/32 (3.1%)
Palmar-plantar erythrodysesthesia syndrome	1/32 (3.1%)
Pruritis	1/32 (3.1%)
Rash	4/32 (12.5%)
Rash erythematous	1/32 (3.1%)
Skin discoloration	1/32 (3.1%)
Urticaria	2/32 (6.3%)
Vascular disorders
Ecchymosis	1/32 (3.1%)
Hypertension	1/32 (3.1%)
Hypotension	1/32 (3.1%)
Orthostatic hypotension	1/32 (3.1%)
Phlebitis	1/32 (3.1%)

Limitations/Caveats

The study was closed to enrollment when it became clear that enrollment was too slow to complete the planned enrollment target of 45 patients within the time frame allowed. Response rate was unable to be assessed due to missingness of required data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A copy of the disclosure must be given to Millennium for review at least 30 days before it is submitted for publication or disclosure. If a Development is contained in the disclosure, Research Organization and/or Principal Investigator defer publication or disclosure for 90 days from the time Millennium notifies that it wants to file a patent application on the Development provided such notice was provided by Millennium within 30 days of the copy first provided to Millennium.