Ixabepilone in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus Previously Treated With Chemotherapy

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01220609
• Collaborator: NRG Oncology (Other)
• Enrollment: 26
• Locations: 72
• Arm: 1
• Duration (Months): 62
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying the side effects and how well ixabepilone works in treating patients with recurrent or persistent leiomyosarcoma of the uterus previously treated with chemotherapy. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Uterine Corpus Sarcoma; Uterine Corpus Leiomyosarcoma	Drug: Ixabepilone; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the response rate (complete and partial responses by RECIST 1.1) of ixabepilone in patients with recurrent or persistent leiomyosarcoma of the uterus who have failed one previous chemotherapy regimen.

2. To determine the nature and degree of toxicity of ixabepilone as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 in this cohort of patients.

SECONDARY OBJECTIVES:

1. To determine the duration of progression-free survival (PFS) and overall survival (OS).

2. To determine the level of beta-III tubulin expression measured by IHC in women with leiomyosarcoma.

3. To determine if beta-III tubulin expression as measured by IHC predicts response to ixabepilone in women with leiomyosarcoma.

OUTLINE:

Patients receive ixabepilone intravenously (IV) over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Ixabepilone (NSC #710428) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ixabepilone) Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Ixabepilone; Given IV; Other Names: BMS 247550 BMS-247550 ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Tumor Response [Every other cycle for the first 6 months; then every 3 months thereafter; up to 5 years.]

   Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.

2. Frequency and Severity of Adverse Events as Assessed by NCI CTCAE v. 4.0 [Every cycle until completion of study treatment up to 30 days after stopping study treatment]

Secondary Outcome Measures

1. Progression-free Survival [From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.]

   Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.

2. Overall Survival [From study entry to death or last contact, up to 5 years of follow-up.]

   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed uterine leiomyosarcoma

• Persistent or recurrent disease that is refractory to curative or established treatments

• Histologic confirmation of the original primary tumor is required

• Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded)

• Each lesion must be ≥ 10 mm by CT scan, MRI, or caliper measurement by clinical exam OR ≥ 20 mm by chest x-ray

• Lymph nodes must be ≥ 15 mm in short axis by CT scan or MRI

• Must have ≥ 1 "target lesion" to assess response

• Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy

• Not eligible for a higher priority GOG protocol, if one exists

• Must have had 1 prior cytotoxic regimen that included a taxane regimen for management of leiomyosarcoma

• Single-agent or multi-agent therapy allowed

• Patients who did not receive prior therapy with a taxane (e.g., docetaxel) must receive a second regimen that includes a taxane

• No known brain metastases

• GOG performance status 0-2

• Life expectancy > 6 months

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• AST ≤ 3 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Peripheral neuropathy (sensory or mother) ≤ grade 1

• Negative pregnancy test

• Not pregnant or nursing

• Fertile patients must use effective contraception prior to and for the duration of study participation

• Free of active infection requiring antibiotics

• Uncomplicated urinary tract infection allowed

• No other invasive malignancy except non-melanoma skin cancer or curatively treated localized cancer of the breast, head and neck, or skin that was completed more than 3 years ago and the patient remains free of recurrence or metastatic disease

• No history of a severe hypersensitivity reaction to agents containing Cremophor EL or its derivatives (e.g., polyoxyethylated castor oil)

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina

• Cardiac arrhythmia

• Psychiatric illness and/or social situations that would limit compliance with study requirements

• No concurrent amifostine or other protective agents

• Recovered from effects of recent surgery, radiotherapy, or chemotherapy

• At least 1 week since prior hormonal therapy

• Hormonal therapy (cytotoxic or non-cytotoxic) not counted as prior regimen

• At least 3 weeks since any other prior therapy directed to the malignant tumor, including immunologic agents

• At least 4 weeks since prior radiation therapy

• One prior non-cytotoxic (biologic or cytostatic) regimen, administered as part of the previous cytotoxic regimen or in addition to it, allowed

• Non-cytotoxic agents include, but are not limited to, the following:

• Monoclonal antibodies

• Cytokines

• Small-molecule inhibitors of signal transduction

• More than 3 years since radiotherapy for localized cancer of the breast, head and neck, or skin provided patient remains free of recurrence or metastatic disease

• No prior ixabepilone

• No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of uterine leiomyosarcoma within the past 3 years

• Prior chemotherapy for localized breast cancer allowed provided it was completed more than 3 years ago and patient remains free of recurrent or metastatic disease

• No other concurrent investigational agents

• No concurrent strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, voriconazole, or grapefruit juice) or CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifampicin, rifabutin, phenobarbital, or St. John wort)

• No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gynecologic Oncology Group of Arizona	Phoenix	Arizona	United States	85012
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
4	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
5	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
6	Hartford Hospital	Hartford	Connecticut	United States	06102
7	Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
8	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
9	Florida Gynecologic Oncology	Fort Myers	Florida	United States	33905
10	John B Amos Cancer Center	Columbus	Georgia	United States	31904
11	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
12	Rush University Medical Center	Chicago	Illinois	United States	60612
13	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
14	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
15	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
16	Cadence Cancer Center in Warrenville	Warrenville	Illinois	United States	60555
17	Saint Vincent Oncology Center	Indianapolis	Indiana	United States	46260
18	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
19	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
20	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
21	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan	United States	48106
22	Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48124
23	Henry Ford Hospital	Detroit	Michigan	United States	48202
24	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
25	Hurley Medical Center	Flint	Michigan	United States	48502
26	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
27	Allegiance Health	Jackson	Michigan	United States	49201
28	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
29	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
30	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
31	Sparrow Hospital	Lansing	Michigan	United States	48912
32	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
33	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
34	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
35	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
36	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
37	Singing River Hospital	Pascagoula	Mississippi	United States	39581
38	Phelps County Regional Medical Center	Rolla	Missouri	United States	65401
39	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
40	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
41	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
42	Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield	Springfield	Missouri	United States	65804
43	CoxHealth South Hospital	Springfield	Missouri	United States	65807
44	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
45	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
46	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
47	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
48	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
49	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
50	Case Western Reserve University	Cleveland	Ohio	United States	44106
51	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
52	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
53	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
54	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
55	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
56	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
57	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
58	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
59	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
60	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
61	Geisinger Medical Group	State College	Pennsylvania	United States	16801
62	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania	United States	18711
63	Women and Infants Hospital	Providence	Rhode Island	United States	02905
64	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina	United States	29605
65	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina	United States	29615
66	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina	United States	29307
67	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
68	University of Virginia	Charlottesville	Virginia	United States	22908
69	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
70	D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
71	Oconomowoc Memorial Hospital-ProHealth Care Inc	Oconomowoc	Wisconsin	United States	53066-3896
72	Waukesha Memorial Hospital - ProHealth Care	Waukesha	Wisconsin	United States	53188

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Linda Duska, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01220609
• Other Study ID Numbers: NCI-2011-02656; NCI-2011-02656; CDR0000686644; GOG-0131H; U10CA027469; U10CA180868
• First Posted: Oct 14, 2010
• Last Update Posted: Aug 8, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Leiomyosarcoma; Recurrence; Epothilones

Study Results

Participant Flow

Arm/Group Title	Ixabepilone
Arm/Group Description	Ixabepilone administered at 40 mg/m2 IV infusion over 3 hours on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment
Period Title: Overall Study
STARTED	26
COMPLETED	23
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Ixabepilone
Arm/Group Description	Ixabepilone administered at 40 mg/m2 IV infusion over 3 hours on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment
Overall Participants	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (7.1)
Age, Customized (participants) [Number]
40-49 years	5 21.7%
50-59 years	12 52.2%
60-69 years	6 26.1%
Sex: Female, Male (Count of Participants)
Female	23 100%
Male	0 0%
Histologic Type (participants) [Number]
Leiomyosarcoma	22 95.7%
Carcinosarcoma, malignant mixed Mullerian tumor	1 4.3%

Outcome Measures

1. Primary Outcome

Title	Tumor Response
Description	Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time Frame	Every other cycle for the first 6 months; then every 3 months thereafter; up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Ixabepilone
Arm/Group Description	Ixabepilone administered at 40 mg/m2 IV infusion over 3 hours on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment
Measure Participants	23
Number (90% Confidence Interval) [percentage of participants]	0 0%

2. Primary Outcome

Title	Frequency and Severity of Adverse Events as Assessed by NCI CTCAE v. 4.0
Time Frame	Every cycle until completion of study treatment up to 30 days after stopping study treatment

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients.

Arm/Group Title	Grade 0	Grade 1 (CTCAE v 4.0)	Grade 2 (CTCAE v 4.0)	Grade 3 (CTCAE v 4.0)	Grade 4 (CTCAE v 4.0)	Grade 5 (CTCAE v 4.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 4.0	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 4.0	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 4.0	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 4.0	Number of patients who experienced a grade 5 event using Common Terminology Criteria version 4.0
Measure Participants	23	23	23	23	23	23
Leukopenia	5 21.7%	5 NaN	6 NaN	5 NaN	2 NaN	0 NaN
Thrombocytopenia	17 73.9%	6 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Neutropenia	8 34.8%	4 NaN	4 NaN	3 NaN	4 NaN	0 NaN
Anemia	2 8.7%	10 NaN	6 NaN	5 NaN	0 NaN	0 NaN
Platelet count decreased	17 73.9%	6 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Nausea	16 69.6%	4 NaN	3 NaN	0 NaN	0 NaN	0 NaN
Vomiting	19 82.6%	3 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Mucositis	20 87%	2 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Constipation	15 65.2%	7 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Diarrhea	18 78.3%	5 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Fatigue	10 43.5%	10 NaN	1 NaN	2 NaN	0 NaN	0 NaN
Anorexia	19 82.6%	2 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Musculoskeletal/Connective tissue	19 82.6%	3 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Myalgia	20 87%	2 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Perpheral sensory neuropathy	17 73.9%	4 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Dizziness	20 87%	3 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Dyspnea	19 82.6%	2 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Alopecia	13 56.5%	4 NaN	6 NaN	0 NaN	0 NaN	0 NaN

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
Time Frame	From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Ixabepilone
Arm/Group Description	Ixabepilone administered at 40 mg/m2 IV infusion over 3 hours on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment
Measure Participants	23
Median (95% Confidence Interval) [months]	1.4

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame	From study entry to death or last contact, up to 5 years of follow-up.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Ixabepilone
Arm/Group Description	Ixabepilone administered at 40 mg/m2 IV infusion over 3 hours on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment
Measure Participants	23
Median (95% Confidence Interval) [months]	7.6

Adverse Events

Time Frame	All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.
Arm/Group Title	Ixabepilone
Arm/Group Description	Ixabepilone administered at 40 mg/m2 IV infusion over 3 hours on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment
All Cause Mortality
	Ixabepilone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ixabepilone
	Affected / at Risk (%)	# Events
Total	9/23 (39.1%)
Gastrointestinal disorders
Dysphagia	1/23 (4.3%)
Colonic Perforation	1/23 (4.3%)
Abdominal Pain	1/23 (4.3%)
General disorders
Pain	1/23 (4.3%)
Investigations
Neutrophil Count Decreased	3/23 (13%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant And Unspecified	1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/23 (4.3%)
Dyspnea	1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Ixabepilone
	Affected / at Risk (%)	# Events
Total	23/23 (100%)
Blood and lymphatic system disorders
Anemia	21/23 (91.3%)
Cardiac disorders
Sinus Tachycardia	1/23 (4.3%)
Chest Pain - Cardiac	1/23 (4.3%)
Ear and labyrinth disorders
Tinnitus	2/23 (8.7%)
External Ear Inflammation	1/23 (4.3%)
Eye disorders
Blurred Vision	1/23 (4.3%)
Gastrointestinal disorders
Dysphagia	1/23 (4.3%)
Dyspepsia	1/23 (4.3%)
Constipation	9/23 (39.1%)
Diarrhea	5/23 (21.7%)
Vomiting	4/23 (17.4%)
Bloating	1/23 (4.3%)
Abdominal Pain	1/23 (4.3%)
Mucositis Oral	3/23 (13%)
Ileus	1/23 (4.3%)
Oral Pain	1/23 (4.3%)
Abdominal Distension	1/23 (4.3%)
Nausea	7/23 (30.4%)
Gastroesophageal Reflux Disease	1/23 (4.3%)
General disorders
Pain	1/23 (4.3%)
Non-Cardiac Chest Pain	1/23 (4.3%)
Edema Limbs	3/23 (13%)
Fatigue	13/23 (56.5%)
Fever	1/23 (4.3%)
Infusion Related Reaction	1/23 (4.3%)
Immune system disorders
Allergic Reaction	1/23 (4.3%)
Infections and infestations
Urinary Tract Infection	1/23 (4.3%)
Investigations
Weight Loss	2/23 (8.7%)
Weight Gain	1/23 (4.3%)
Platelet Count Decreased	6/23 (26.1%)
Neutrophil Count Decreased	15/23 (65.2%)
Blood Bilirubin Increased	1/23 (4.3%)
White Blood Cell Decreased	18/23 (78.3%)
Aspartate Aminotransferase Increased	3/23 (13%)
Alkaline Phosphatase Increased	3/23 (13%)
Alanine Aminotransferase Increased	1/23 (4.3%)
Metabolism and nutrition disorders
Hyponatremia	3/23 (13%)
Hypokalemia	2/23 (8.7%)
Hypocalcemia	2/23 (8.7%)
Hypoalbuminemia	2/23 (8.7%)
Hyperglycemia	3/23 (13%)
Dehydration	1/23 (4.3%)
Anorexia	4/23 (17.4%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	6/23 (26.1%)
Myalgia	3/23 (13%)
Generalized Muscle Weakness	1/23 (4.3%)
Bone Pain	1/23 (4.3%)
Back Pain	2/23 (8.7%)
Arthralgia	4/23 (17.4%)
Musculoskeletal And Connective Tissue Disorder -	1/23 (4.3%)
Nervous system disorders
Peripheral Sensory Neuropathy	7/23 (30.4%)
Paresthesia	3/23 (13%)
Movements Involuntary	1/23 (4.3%)
Headache	1/23 (4.3%)
Dysgeusia	1/23 (4.3%)
Dizziness	3/23 (13%)
Psychiatric disorders
Insomnia	2/23 (8.7%)
Anxiety	2/23 (8.7%)
Renal and urinary disorders
Urinary Frequency	1/23 (4.3%)
Hematuria	1/23 (4.3%)
Bladder Spasm	1/23 (4.3%)
Acute Kidney Injury	1/23 (4.3%)
Reproductive system and breast disorders
Vaginal Hemorrhage	1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/23 (4.3%)
Pleural Effusion	1/23 (4.3%)
Productive Cough	1/23 (4.3%)
Dyspnea	6/23 (26.1%)
Cough	1/23 (4.3%)
Skin and subcutaneous tissue disorders
Skin Hyperpigmentation	1/23 (4.3%)
Scalp Pain	1/23 (4.3%)
Rash Acneiform	2/23 (8.7%)
Nail Discoloration	1/23 (4.3%)
Erythema Multiforme	1/23 (4.3%)
Alopecia	10/23 (43.5%)
Vascular disorders
Thromboembolic Event	1/23 (4.3%)
Lymphedema	2/23 (8.7%)
Hypotension	1/23 (4.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.