Gemcitabine Hydrochloride and Docetaxel With or Without Bevacizumab in Treating Patients With Advanced or Recurrent Uterine Leiomyosarcoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01012297
• Collaborator: NRG Oncology (Other)
• Enrollment: 107
• Locations: 201
• Arms: 2
• Duration (Months): 70
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial is studying gemcitabine hydrochloride, docetaxel, and bevacizumab to see how well they work compared with gemcitabine hydrochloride, docetaxel, and a placebo in treating patients with advanced or recurrent uterine leiomyosarcoma. Drugs used in chemotherapy, such as gemcitabine hydrochloride and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether gemcitabine hydrochloride and docetaxel are more effective when given with or without bevacizumab in treating uterine leiomyosarcoma.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Uterine Corpus Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Corpus Leiomyosarcoma	Biological: Bevacizumab; Drug: Docetaxel; Biological: Filgrastim; Drug: Gemcitabine Hydrochloride; Biological: Pegfilgrastim; Other: Placebo	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To determine whether the addition of bevacizumab to fixed-dose rate gemcitabine-docetaxel reduces the progression-free survival (PFS) event rate when compared to gemcitabine-docetaxel plus placebo in patients with advanced or recurrent uterine leiomyosarcoma (LMS).

SECONDARY OBJECTIVES:

1. To determine the objective response rate, as measured by RECIST, of patients treated with fixed-dose rate gemcitabine-docetaxel with bevacizumab, compared with the objective response rate of patients treated with fixed-dose rate gemcitabine-docetaxel with placebo.

2. To determine if the addition of bevacizumab to the combination of gemcitabine and docetaxel increases overall survival in patients with advanced or recurrent uterine LMS.

3. To determine the toxicity profile of fixed-dose rate gemcitabine-docetaxel with and without bevacizumab in this patient population.

4. To bank formalin-fixed and paraffin-embedded (FFPE) tumor tissue for research.

OUTLINE: This is a multicenter study. Patients are stratified according to prior whole-pelvic radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10.

ARM II: Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, 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: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase III Evaluation of Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Bevacizumab (NSC #704865) Versus Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Placebo in the Treatment of Recurrent or Advanced Leiomyosarcoma of the Uterus
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Gem+Doce+Placebo Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10.	Drug: Docetaxel; Given IV; Other Names: RP56976 Taxotere Taxotere Injection Concentrate ; Biological: Filgrastim; Given SC; Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim ; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd Difluorodeoxycytidine Hydrochloride Gemzar LY-188011 ; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01 filgrastim-SD/01 Neulasta SD-01 SD-01 sustained duration G-CSF ; Other: Placebo; Given IV; Other Names: placebo therapy PLCB sham therapy
Experimental: Arm II Gem+Doce+Bev Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10.	Biological: Bevacizumab; Given IV; Other Names: Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF rhuMAb Avastin Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF ; Drug: Docetaxel; Given IV; Other Names: RP56976 Taxotere Taxotere Injection Concentrate ; Biological: Filgrastim; Given SC; Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim ; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd Difluorodeoxycytidine Hydrochloride Gemzar LY-188011 ; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01 filgrastim-SD/01 Neulasta SD-01 SD-01 sustained duration G-CSF

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]

   Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan. Assessed with a log-rank test stratified by whether the patient had whole pelvic radiotherapy prior to starting the study treatment. The product-limit method will be used to estimate the cumulative distribution of PFS for the patients assigned to each treatment group.

Secondary Outcome Measures

1. Overall Survival [Up to 5 years]

   Overall survival (OS) was defined as the number of months between study enrollment and death from any cause. Patients still alive at the last followup were censored on the date of last CT Scan. The product-limit method will be used to estimate the cumulative distribution of overall survival times for the patients assigned to each treatment group.

2. Frequency and Severity of Adverse Effects as Assessed by the CTCAE Version 4.0 [Up to 5 years]

   Count of participants with Adverse events (AEs) that are CTCAE Grade 3 or worse. Please refer to the adverse event reporting for more detail.

3. Objective Response Rate as Measured by RECIST 1.1 Criteria [Up to 5 years]

   "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have advanced or recurrent uterine leiomyosarcoma with documented disease progression; histologic confirmation of the original primary tumor is required

• All patients must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; 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 at least 90 days following completion of radiation therapy

• Patients must have a GOG Performance Status of 0, 1, or 2

• Patients must have recovered from effects of recent surgery, radiotherapy or other therapy

• Patients should be free of active infection requiring antibiotics (with the exception of an uncomplicated UTI)

• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to first day of study treatment; continuation of hormone replacement therapy is permitted

• Platelet count greater than or equal to 100,000/mm^3

• ANC count greater than or equal to 1,500/mm^3

• Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), per NCI CTCAE Version 4.0 Grade 1

• Bilirubin within normal range (CTCAE Version 4 Grade 0)

• SGOT and alkaline phosphatase less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade 1)

• SGOT less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade 1

• Alkaline phosphatase less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade 1

• Neuropathy (sensory and motor) less than or equal to Grade 1 per the CTCAE Version 4.0.

• No history of transient ischemic attack (TIA) or stroke or CNS hemorrhage within the past 6 months

• Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended

• PT such that international normalized ratio (INR) is =< 1.5 and a PTT =< 1.5 times the institutional upper limit of normal (or an in-therapeutic-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin)

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

• Patients must meet pre-entry requirements

• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception

Exclusion Criteria:

• Patients who have received prior cytotoxic chemotherapy for management of uterine sarcoma; patients who have received prior VEGF-pathway targeted agent such as bevacizumab, PTK787, VEGF-trap, or who have received prior treatment with a multi-kinase inhibitor such as sorafenib or sunitinib are not eligible

• Patients who have had prior therapy with docetaxel or gemcitabine or bevacizumab

• Patients with a history of other invasive malignancies, with the exceptions of non-melanoma skin cancer, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels; (necessary use of warfarin or low molecular weight heparin is permitted, provided the INR is maintained in the therapeutic range of approximately 2-3)

• Patients with major surgery or significant traumatic injury within 28 days prior to study entry

• Patients with a history of abdominal fistula or perforation within the past 12 months

• Patients with a current, serious, non-healing wound, ulcer, or bone fracture

• Patients with history or evidence upon physical examination of CNS disease, including history of primary brain tumor, or any history of brain metastases, or seizures not controlled with standard medical therapy

• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Cardiovascular function; specifically, patient may not have:

• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 100 mm Hg in a patient with no history of hypertension; patients with a history of hypertension before enrollment on study are permitted, but such patients must have BP less than or equal to 140/90 mmHg; use of blood pressure medications to achieve and maintain blood pressure control is permitted

• Myocardial infarction or unstable angina within 6 months of the first date of bevacizumab/placebo therapy

• New York Heart Association (NYHA) Grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication; women who have received prior treatment with an anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction < 50% will be excluded from the study

• Grade 1, Category 2 or greater, peripheral vascular disease; patient cannot have anything worse than mild, symptomatic claudication with exercise

• History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of bevacizumab/placebo therapy

• History of pulmonary embolism or deep vein thrombosis in the past 6 months

• Patients with, or with anticipation of, invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab/placebo therapy

• Major surgical procedure anticipated during the course of the study.

• Minor surgical procedures (i.e., mediport insertion), fine needle aspirates, or core biopsies within 7 days prior to the first date of bevacizumab/placebo therapy

• Patients who are pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
2	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
3	John Muir Medical Center-Concord Campus	Concord	California	United States	94520
4	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
5	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
6	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
7	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
8	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
9	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
10	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
11	University of California San Diego	San Diego	California	United States	92103
12	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
13	Olive View-University of California Los Angeles Medical Center	Sylmar	California	United States	91342
14	John Muir Medical Center-Walnut Creek	Walnut Creek	California	United States	94598
15	The Medical Center of Aurora	Aurora	Colorado	United States	80012
16	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
17	Boulder Community Hospital	Boulder	Colorado	United States	80301
18	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
19	Porter Adventist Hospital	Denver	Colorado	United States	80210
20	Exempla Saint Joseph Hospital	Denver	Colorado	United States	80218
21	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
22	Rose Medical Center	Denver	Colorado	United States	80220
23	Colorado Cancer Research Program CCOP	Denver	Colorado	United States	80224-2522
24	Rocky Mountain Gynecologic Oncology PC	Englewood	Colorado	United States	80110
25	Swedish Medical Center	Englewood	Colorado	United States	80113
26	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81502
27	North Colorado Medical Center	Greeley	Colorado	United States	80631
28	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
29	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
30	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
31	Longmont United Hospital	Longmont	Colorado	United States	80501
32	McKee Medical Center	Loveland	Colorado	United States	80539
33	Parker Adventist Hospital	Parker	Colorado	United States	80138
34	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
35	North Suburban Medical Center	Thornton	Colorado	United States	80229
36	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
37	Hartford Hospital	Hartford	Connecticut	United States	06102
38	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
39	Beebe Medical Center	Lewes	Delaware	United States	19958
40	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
41	Washington Hospital Center	Washington	District of Columbia	United States	20010
42	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
43	Mercy Hospital	Miami	Florida	United States	33133
44	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
45	Florida Hospital Orlando	Orlando	Florida	United States	32803
46	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
47	Georgia Regents University Medical Center	Augusta	Georgia	United States	30912
48	John B Amos Cancer Center	Columbus	Georgia	United States	31904
49	Memorial University Medical Center	Savannah	Georgia	United States	31404
50	Northwestern University	Chicago	Illinois	United States	60611
51	Rush University Medical Center	Chicago	Illinois	United States	60612
52	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
53	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
54	Memorial Medical Center	Springfield	Illinois	United States	62781
55	Cadence Cancer Center in Warrenville	Warrenville	Illinois	United States	60555
56	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
57	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
58	Elkhart General Hospital	Elkhart	Indiana	United States	46515
59	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
60	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana	United States	46237
61	Gynecologic Oncology of Indiana	Indianapolis	Indiana	United States	46237
62	Saint Vincent Oncology Center	Indianapolis	Indiana	United States	46260
63	Community Howard Regional Health	Kokomo	Indiana	United States	46904
64	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
65	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
66	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
67	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
68	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
69	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
70	South Bend Clinic	South Bend	Indiana	United States	46617
71	Northern Indiana Cancer Research Consortium CCOP	South Bend	Indiana	United States	46628
72	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
73	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
74	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
75	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
76	Iowa Oncology Research Association CCOP	Des Moines	Iowa	United States	50309
77	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
78	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
79	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
80	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
81	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
82	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
83	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
84	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
85	Baptist Health Lexington	Lexington	Kentucky	United States	40503
86	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky	United States	40202
87	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
88	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
89	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
90	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
91	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
92	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
93	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
94	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
95	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
96	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
97	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
98	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
99	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
100	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
101	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
102	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
103	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
104	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
105	Michiana Hematology Oncology PC-Niles	Niles	Michigan	United States	49120
106	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
107	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
108	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
109	Munson Medical Center	Traverse City	Michigan	United States	49684
110	Metro Health Hospital	Wyoming	Michigan	United States	49519
111	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
112	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
113	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
114	Unity Hospital	Fridley	Minnesota	United States	55432
115	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
116	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
117	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
118	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
119	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
120	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
121	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
122	Mayo Clinic	Rochester	Minnesota	United States	55905
123	Metro-Minnesota NCI Community Oncology Research Program	Saint Louis Park	Minnesota	United States	55416
124	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
125	Regions Hospital	Saint Paul	Minnesota	United States	55101
126	United Hospital	Saint Paul	Minnesota	United States	55102
127	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
128	Lakeview Hospital	Stillwater	Minnesota	United States	55082
129	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
130	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
131	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
132	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
133	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
134	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
135	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
136	CoxHealth South Hospital	Springfield	Missouri	United States	65807
137	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
138	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
139	Center of Hope at Renown Medical Center	Reno	Nevada	United States	89502
140	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
141	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
142	Morristown Medical Center	Morristown	New Jersey	United States	07960
143	Virtua Memorial	Mount Holly	New Jersey	United States	08060
144	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
145	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
146	Overlook Hospital	Summit	New Jersey	United States	07902
147	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey	United States	08043
148	University of New Mexico	Albuquerque	New Mexico	United States	87102
149	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
150	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
151	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
152	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
153	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
154	Mount Sinai Medical Center	New York	New York	United States	10029
155	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
156	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
157	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
158	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
159	Carolinas HealthCare System NorthEast	Concord	North Carolina	United States	28025
160	Duke University Medical Center	Durham	North Carolina	United States	27710
161	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
162	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
163	University of Cincinnati	Cincinnati	Ohio	United States	45267
164	Case Western Reserve University	Cleveland	Ohio	United States	44106
165	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
166	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
167	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
168	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
169	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
170	Kettering Medical Center	Kettering	Ohio	United States	45429
171	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
172	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
173	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
174	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
175	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
176	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
177	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
178	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
179	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
180	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
181	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
182	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
183	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
184	Geisinger Medical Group	State College	Pennsylvania	United States	16801
185	Reading Hospital	West Reading	Pennsylvania	United States	19611
186	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
187	Women and Infants Hospital	Providence	Rhode Island	United States	02905
188	Medical University of South Carolina	Charleston	South Carolina	United States	29425
189	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
190	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
191	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
192	Parkland Memorial Hospital	Dallas	Texas	United States	75235
193	Zale Lipshy University Hospital	Dallas	Texas	United States	75235
194	Clements University Hospital	Dallas	Texas	United States	75390
195	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
196	Baylor All Saints Medical Center at Fort Worth	Fort Worth	Texas	United States	76104
197	M D Anderson Cancer Center	Houston	Texas	United States	77030
198	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
199	University of Vermont Medical Center	Burlington	Vermont	United States	05401
200	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
201	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Martee Hensley, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01012297
• Other Study ID Numbers: NCI-2010-01738; NCI-2010-01738; CDR0000659024; GOG-0250; GOG-0250; GOG-0250; U10CA027469
• First Posted: Nov 13, 2009
• Last Update Posted: Sep 2, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Sarcoma; Leiomyosarcoma; Recurrence; Gemcitabine; Bevacizumab; Antineoplastic Agents, Immunological; Docetaxel; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim; Immunoglobulin G

Study Results

Participant Flow

Arm/Group Title	Arm I Gem+Doce+Placebo	Arm II Gem+Doce+Bev
Arm/Group Description	Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC Placebo: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Bevacizumab: Given IV Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC
Period Title: Overall Study
STARTED	54	53
COMPLETED	54	53
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I Gem+Doce+Placebo	Arm II Gem+Doce+Bev	Total
Arm/Group Description	Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC Placebo: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Bevacizumab: Given IV Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC	Total of all reporting groups
Overall Participants	54	53	107
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (8.1)	54.0 (8.7)	55.7 (8.6)
Age, Customized (Count of Participants)
20-29 years	0 0%	1 1.9%	1 0.9%
30-39 years	0 0%	3 5.7%	3 2.8%
40-49 years	11 20.4%	12 22.6%	23 21.5%
50-59 years	24 44.4%	25 47.2%	49 45.8%
60-69 years	19 35.2%	12 22.6%	31 29%
Sex: Female, Male (Count of Participants)
Female	54 100%	53 100%	107 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 7.4%	3 5.7%	7 6.5%
Not Hispanic or Latino	48 88.9%	43 81.1%	91 85%
Unknown or Not Reported	2 3.7%	7 13.2%	9 8.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.9%	1 0.9%
Asian	1 1.9%	1 1.9%	2 1.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 11.1%	12 22.6%	18 16.8%
White	46 85.2%	36 67.9%	82 76.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.9%	3 5.7%	4 3.7%
Prior whole pelvic radiation (Count of Participants)
Yes	11 20.4%	11 20.8%	22 20.6%
No	43 79.6%	42 79.2%	85 79.4%
Performance Status (Count of Participants)
0: Asymptomatic	38 70.4%	41 77.4%	79 73.8%
1: Symptomatic, fully ambulatory	15 27.8%	11 20.8%	26 24.3%
2: Symptomatic, in bed < 50% of time	1 1.9%	1 1.9%	2 1.9%
FIGO Stage (Count of Participants)
1	20 37%	11 20.8%	31 29%
2	4 7.4%	0 0%	4 3.7%
3	3 5.6%	5 9.4%	8 7.5%
4	22 40.7%	30 56.6%	52 48.6%
unknown	5 9.3%	7 13.2%	12 11.2%
Cell Type (Count of Participants)
Leiomyosarcoma	52 96.3%	52 98.1%	104 97.2%
Sarcoma, Unsp.	1 1.9%	0 0%	1 0.9%
Carcinsarcoma	0 0%	1 1.9%	1 0.9%
Unknown	1 1.9%	0 0%	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan. Assessed with a log-rank test stratified by whether the patient had whole pelvic radiotherapy prior to starting the study treatment. The product-limit method will be used to estimate the cumulative distribution of PFS for the patients assigned to each treatment group.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Outcome Measure Data

Analysis Population Description

All randomized

Arm/Group Title	Arm I Gem+Doce+Placebo	Arm II Gem+Doce+Bev
Arm/Group Description	Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC Placebo: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Bevacizumab: Given IV Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC
Measure Participants	54	53
Median (95% Confidence Interval) [months]	6.2	4.2

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the number of months between study enrollment and death from any cause. Patients still alive at the last followup were censored on the date of last CT Scan. The product-limit method will be used to estimate the cumulative distribution of overall survival times for the patients assigned to each treatment group.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All randomized

Arm/Group Title	Arm I Gem+Doce+Placebo	Arm II Gem+Doce+Bev
Arm/Group Description	Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC Placebo: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Bevacizumab: Given IV Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC
Measure Participants	54	53
Median (95% Confidence Interval) [months]	26.9	23.3

3. Secondary Outcome

Title	Frequency and Severity of Adverse Effects as Assessed by the CTCAE Version 4.0
Description	Count of participants with Adverse events (AEs) that are CTCAE Grade 3 or worse. Please refer to the adverse event reporting for more detail.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All randomized.

Arm/Group Title	Arm I Gem+Doce+Placebo	Arm II Gem+Doce+Bev
Arm/Group Description	Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC Placebo: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Bevacizumab: Given IV Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC
Measure Participants	54	53
Count of Participants [Participants]	36 66.7%	46 86.8%

4. Secondary Outcome

Title	Objective Response Rate as Measured by RECIST 1.1 Criteria
Description	"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All randomized

Arm/Group Title	Arm I Gem+Doce+Placebo	Arm II Gem+Doce+Bev
Arm/Group Description	Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC Placebo: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Bevacizumab: Given IV Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC
Measure Participants	54	53
Number (95% Confidence Interval) [percentage of participants]	31.5 58.3%	35.8 67.5%

Adverse Events

Arm/Group Title	Arm I		Arm II
Arm/Group Description	Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC Placebo: Given IV		Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Bevacizumab: Given IV Docetaxel: Given IV Filgrastim: Given SC Gemcitabine Hydrochloride: Given IV Pegfilgrastim: Given SC
All Cause Mortality
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/54 (31.5%)		21/53 (39.6%)
Cardiac disorders
Pericardial Effusion	0/54 (0%)		1/53 (1.9%)
Gastrointestinal disorders
Diarrhea	0/54 (0%)		1/53 (1.9%)
Small Intestinal Obstruction	1/54 (1.9%)		2/53 (3.8%)
Abdominal Pain	1/54 (1.9%)		2/53 (3.8%)
General disorders
Fatigue	2/54 (3.7%)		0/53 (0%)
Immune system disorders
Anaphylaxis	0/54 (0%)		1/53 (1.9%)
Allergic Reaction	1/54 (1.9%)		0/53 (0%)
Infections and infestations
Infections And Infestations - Other	0/54 (0%)		2/53 (3.8%)
Soft Tissue Infection	1/54 (1.9%)		0/53 (0%)
Skin Infection	1/54 (1.9%)		0/53 (0%)
Sepsis	1/54 (1.9%)		0/53 (0%)
Lung Infection	3/54 (5.6%)		2/53 (3.8%)
Catheter Related Infection	1/54 (1.9%)		2/53 (3.8%)
Abdominal Infection	1/54 (1.9%)		0/53 (0%)
Injury, poisoning and procedural complications
Spinal Fracture	0/54 (0%)		1/53 (1.9%)
Hip Fracture	1/54 (1.9%)		0/53 (0%)
Fracture	1/54 (1.9%)		0/53 (0%)
Investigations
Platelet Count Decreased	1/54 (1.9%)		3/53 (5.7%)
Lymphocyte Count Decreased	0/54 (0%)		1/53 (1.9%)
Neutrophil Count Decreased	0/54 (0%)		1/53 (1.9%)
Metabolism and nutrition disorders
Hyperkalemia	1/54 (1.9%)		0/53 (0%)
Hyperglycemia	2/54 (3.7%)		1/53 (1.9%)
Dehydration	2/54 (3.7%)		1/53 (1.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/54 (1.9%)		0/53 (0%)
Pneumonitis	0/54 (0%)		1/53 (1.9%)
Dyspnea	0/54 (0%)		1/53 (1.9%)
Vascular disorders
Thromboembolic Event	2/54 (3.7%)		3/53 (5.7%)
Other (Not Including Serious) Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/54 (94.4%)		51/53 (96.2%)
Blood and lymphatic system disorders
Thrombotic Thrombocytopenic Purpura	0/54 (0%)		1/53 (1.9%)
Blood And Lymphatic System Disorders - Other	1/54 (1.9%)		2/53 (3.8%)
Anemia	47/54 (87%)		48/53 (90.6%)
Cardiac disorders
Palpitations	2/54 (3.7%)		3/53 (5.7%)
Pericardial Effusion	1/54 (1.9%)		1/53 (1.9%)
Sinus Tachycardia	3/54 (5.6%)		5/53 (9.4%)
Chest Pain - Cardiac	1/54 (1.9%)		0/53 (0%)
Ear and labyrinth disorders
Vertigo	1/54 (1.9%)		1/53 (1.9%)
Tinnitus	2/54 (3.7%)		1/53 (1.9%)
Hearing Impaired	0/54 (0%)		1/53 (1.9%)
Ear Pain	1/54 (1.9%)		4/53 (7.5%)
Eye disorders
Eye Disorders - Other	1/54 (1.9%)		2/53 (3.8%)
Watering Eyes	1/54 (1.9%)		9/53 (17%)
Eye Pain	0/54 (0%)		1/53 (1.9%)
Conjunctivitis	1/54 (1.9%)		1/53 (1.9%)
Blurred Vision	6/54 (11.1%)		4/53 (7.5%)
Dry Eye	1/54 (1.9%)		2/53 (3.8%)
Gastrointestinal disorders
Dysphagia	3/54 (5.6%)		3/53 (5.7%)
Dyspepsia	6/54 (11.1%)		3/53 (5.7%)
Dry Mouth	1/54 (1.9%)		5/53 (9.4%)
Colitis	1/54 (1.9%)		0/53 (0%)
Constipation	24/54 (44.4%)		26/53 (49.1%)
Diarrhea	19/54 (35.2%)		22/53 (41.5%)
Vomiting	14/54 (25.9%)		16/53 (30.2%)
Bloating	1/54 (1.9%)		3/53 (5.7%)
Stomach Pain	1/54 (1.9%)		1/53 (1.9%)
Small Intestinal Obstruction	0/54 (0%)		2/53 (3.8%)
Anal Hemorrhage	1/54 (1.9%)		2/53 (3.8%)
Rectal Fistula	0/54 (0%)		1/53 (1.9%)
Rectal Mucositis	1/54 (1.9%)		0/53 (0%)
Abdominal Pain	16/54 (29.6%)		15/53 (28.3%)
Rectal Hemorrhage	5/54 (9.3%)		2/53 (3.8%)
Oral Dysesthesia	2/54 (3.7%)		1/53 (1.9%)
Mucositis Oral	14/54 (25.9%)		15/53 (28.3%)
Gastrointestinal Disorders - Other	1/54 (1.9%)		3/53 (5.7%)
Oral Hemorrhage	0/54 (0%)		4/53 (7.5%)
Gastrointestinal Pain	1/54 (1.9%)		1/53 (1.9%)
Gingival Pain	1/54 (1.9%)		1/53 (1.9%)
Oral Pain	2/54 (3.7%)		3/53 (5.7%)
Abdominal Distension	5/54 (9.3%)		1/53 (1.9%)
Nausea	35/54 (64.8%)		29/53 (54.7%)
Gastroesophageal Reflux Disease	2/54 (3.7%)		6/53 (11.3%)
Rectal Pain	0/54 (0%)		1/53 (1.9%)
Esophagitis	1/54 (1.9%)		0/53 (0%)
Hemorrhoidal Hemorrhage	3/54 (5.6%)		3/53 (5.7%)
Hemorrhoids	1/54 (1.9%)		1/53 (1.9%)
Ascites	0/54 (0%)		1/53 (1.9%)
Toothache	1/54 (1.9%)		0/53 (0%)
Esophageal Pain	1/54 (1.9%)		1/53 (1.9%)
Flatulence	0/54 (0%)		1/53 (1.9%)
General disorders
General Disorders And Administration Site Conditio	2/54 (3.7%)		0/53 (0%)
Pain	13/54 (24.1%)		9/53 (17%)
Localized Edema	0/54 (0%)		1/53 (1.9%)
Injection Site Reaction	2/54 (3.7%)		2/53 (3.8%)
Infusion Site Extravasation	1/54 (1.9%)		0/53 (0%)
Flu Like Symptoms	2/54 (3.7%)		2/53 (3.8%)
Edema Trunk	2/54 (3.7%)		0/53 (0%)
Non-Cardiac Chest Pain	4/54 (7.4%)		3/53 (5.7%)
Edema Limbs	23/54 (42.6%)		12/53 (22.6%)
Edema Face	4/54 (7.4%)		3/53 (5.7%)
Fatigue	45/54 (83.3%)		42/53 (79.2%)
Fever	17/54 (31.5%)		19/53 (35.8%)
Chills	3/54 (5.6%)		3/53 (5.7%)
Infusion Related Reaction	2/54 (3.7%)		1/53 (1.9%)
Hepatobiliary disorders
Cholecystitis	0/54 (0%)		1/53 (1.9%)
Immune system disorders
Allergic Reaction	7/54 (13%)		1/53 (1.9%)
Cytokine Release Syndrome	1/54 (1.9%)		0/53 (0%)
Infections and infestations
Infections And Infestations - Other	2/54 (3.7%)		1/53 (1.9%)
Upper Respiratory Infection	2/54 (3.7%)		1/53 (1.9%)
Tooth Infection	1/54 (1.9%)		3/53 (5.7%)
Skin Infection	2/54 (3.7%)		0/53 (0%)
Sinusitis	2/54 (3.7%)		1/53 (1.9%)
Papulopustular Rash	1/54 (1.9%)		0/53 (0%)
Nail Infection	1/54 (1.9%)		3/53 (5.7%)
Mucosal Infection	3/54 (5.6%)		1/53 (1.9%)
Pelvic Infection	0/54 (0%)		1/53 (1.9%)
Lung Infection	2/54 (3.7%)		2/53 (3.8%)
Eye Infection	0/54 (0%)		1/53 (1.9%)
Device Related Infection	2/54 (3.7%)		1/53 (1.9%)
Vaginal Infection	1/54 (1.9%)		0/53 (0%)
Urinary Tract Infection	8/54 (14.8%)		7/53 (13.2%)
Catheter Related Infection	0/54 (0%)		2/53 (3.8%)
Bronchial Infection	1/54 (1.9%)		0/53 (0%)
Enterocolitis Infectious	1/54 (1.9%)		0/53 (0%)
Bladder Infection	0/54 (0%)		1/53 (1.9%)
Lip Infection	1/54 (1.9%)		0/53 (0%)
Anorectal Infection	0/54 (0%)		1/53 (1.9%)
Injury, poisoning and procedural complications
Injury, Poisoning And Procedural Complications - O	1/54 (1.9%)		0/53 (0%)
Vascular Access Complication	0/54 (0%)		1/53 (1.9%)
Tracheostomy Site Bleeding	1/54 (1.9%)		0/53 (0%)
Fall	1/54 (1.9%)		0/53 (0%)
Bruising	2/54 (3.7%)		4/53 (7.5%)
Ankle Fracture	1/54 (1.9%)		0/53 (0%)
Investigations
Investigations - Other	2/54 (3.7%)		0/53 (0%)
Weight Loss	4/54 (7.4%)		6/53 (11.3%)
Weight Gain	4/54 (7.4%)		5/53 (9.4%)
Platelet Count Decreased	39/54 (72.2%)		45/53 (84.9%)
Lymphocyte Count Decreased	2/54 (3.7%)		5/53 (9.4%)
Inr Increased	2/54 (3.7%)		0/53 (0%)
Creatinine Increased	2/54 (3.7%)		3/53 (5.7%)
Neutrophil Count Decreased	26/54 (48.1%)		25/53 (47.2%)
Blood Bilirubin Increased	2/54 (3.7%)		1/53 (1.9%)
White Blood Cell Decreased	28/54 (51.9%)		33/53 (62.3%)
Aspartate Aminotransferase Increased	9/54 (16.7%)		10/53 (18.9%)
Alkaline Phosphatase Increased	16/54 (29.6%)		17/53 (32.1%)
Alanine Aminotransferase Increased	14/54 (25.9%)		10/53 (18.9%)
Activated Partial Thromboplastin Time Prolonged	2/54 (3.7%)		1/53 (1.9%)
Metabolism and nutrition disorders
Metabolism And Nutrition Disorders - Other	2/54 (3.7%)		1/53 (1.9%)
Hypophosphatemia	1/54 (1.9%)		2/53 (3.8%)
Hyponatremia	8/54 (14.8%)		5/53 (9.4%)
Hypomagnesemia	6/54 (11.1%)		4/53 (7.5%)
Hypokalemia	8/54 (14.8%)		8/53 (15.1%)
Hypoglycemia	1/54 (1.9%)		1/53 (1.9%)
Hypocalcemia	12/54 (22.2%)		8/53 (15.1%)
Hypoalbuminemia	14/54 (25.9%)		9/53 (17%)
Hypernatremia	1/54 (1.9%)		1/53 (1.9%)
Hypermagnesemia	2/54 (3.7%)		1/53 (1.9%)
Hyperkalemia	2/54 (3.7%)		3/53 (5.7%)
Hyperglycemia	14/54 (25.9%)		7/53 (13.2%)
Hypercalcemia	0/54 (0%)		5/53 (9.4%)
Dehydration	3/54 (5.6%)		2/53 (3.8%)
Anorexia	21/54 (38.9%)		19/53 (35.8%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	13/54 (24.1%)		12/53 (22.6%)
Neck Pain	2/54 (3.7%)		1/53 (1.9%)
Myalgia	11/54 (20.4%)		20/53 (37.7%)
Musculoskeletal Deformity	0/54 (0%)		1/53 (1.9%)
Muscle Weakness Upper Limb	0/54 (0%)		1/53 (1.9%)
Muscle Weakness Lower Limb	2/54 (3.7%)		2/53 (3.8%)
Joint Range Of Motion Decreased	0/54 (0%)		1/53 (1.9%)
Generalized Muscle Weakness	5/54 (9.3%)		3/53 (5.7%)
Flank Pain	2/54 (3.7%)		0/53 (0%)
Chest Wall Pain	1/54 (1.9%)		4/53 (7.5%)
Buttock Pain	0/54 (0%)		2/53 (3.8%)
Bone Pain	13/54 (24.1%)		11/53 (20.8%)
Back Pain	9/54 (16.7%)		9/53 (17%)
Arthritis	1/54 (1.9%)		0/53 (0%)
Arthralgia	10/54 (18.5%)		9/53 (17%)
Musculoskeletal And Connective Tissue Disorder -	1/54 (1.9%)		1/53 (1.9%)
Nervous system disorders
Tremor	1/54 (1.9%)		0/53 (0%)
Spasticity	0/54 (0%)		1/53 (1.9%)
Seizure	1/54 (1.9%)		0/53 (0%)
Peripheral Sensory Neuropathy	21/54 (38.9%)		19/53 (35.8%)
Peripheral Motor Neuropathy	3/54 (5.6%)		3/53 (5.7%)
Paresthesia	2/54 (3.7%)		3/53 (5.7%)
Memory Impairment	1/54 (1.9%)		0/53 (0%)
Lethargy	1/54 (1.9%)		0/53 (0%)
Headache	17/54 (31.5%)		14/53 (26.4%)
Dysgeusia	6/54 (11.1%)		8/53 (15.1%)
Sinus Pain	0/54 (0%)		1/53 (1.9%)
Syncope	1/54 (1.9%)		0/53 (0%)
Dizziness	9/54 (16.7%)		7/53 (13.2%)
Ataxia	1/54 (1.9%)		1/53 (1.9%)
Psychiatric disorders
Restlessness	0/54 (0%)		1/53 (1.9%)
Insomnia	11/54 (20.4%)		10/53 (18.9%)
Depression	5/54 (9.3%)		7/53 (13.2%)
Anxiety	10/54 (18.5%)		9/53 (17%)
Renal and urinary disorders
Renal And Urinary Disorders - Other	2/54 (3.7%)		0/53 (0%)
Urinary Retention	2/54 (3.7%)		0/53 (0%)
Urinary Incontinence	0/54 (0%)		4/53 (7.5%)
Urinary Tract Pain	2/54 (3.7%)		1/53 (1.9%)
Urinary Frequency	0/54 (0%)		2/53 (3.8%)
Proteinuria	2/54 (3.7%)		1/53 (1.9%)
Hemoglobinuria	1/54 (1.9%)		0/53 (0%)
Hematuria	2/54 (3.7%)		2/53 (3.8%)
Cystitis Noninfective	1/54 (1.9%)		0/53 (0%)
Bladder Spasm	0/54 (0%)		1/53 (1.9%)
Reproductive system and breast disorders
Reproductive System And Breast Disorders - Other	0/54 (0%)		1/53 (1.9%)
Vaginal Pain	0/54 (0%)		1/53 (1.9%)
Vaginal Hemorrhage	0/54 (0%)		1/53 (1.9%)
Pelvic Pain	2/54 (3.7%)		1/53 (1.9%)
Vaginal Discharge	0/54 (0%)		3/53 (5.7%)
Breast Pain	1/54 (1.9%)		0/53 (0%)
Respiratory, thoracic and mediastinal disorders
Sore Throat	6/54 (11.1%)		9/53 (17%)
Sneezing	0/54 (0%)		2/53 (3.8%)
Sinus Disorder	0/54 (0%)		2/53 (3.8%)
Postnasal Drip	1/54 (1.9%)		4/53 (7.5%)
Pneumothorax	0/54 (0%)		1/53 (1.9%)
Pneumonitis	2/54 (3.7%)		0/53 (0%)
Pleural Effusion	2/54 (3.7%)		1/53 (1.9%)
Pharyngeal Hemorrhage	0/54 (0%)		1/53 (1.9%)
Nasal Congestion	6/54 (11.1%)		8/53 (15.1%)
Productive Cough	0/54 (0%)		3/53 (5.7%)
Laryngeal Inflammation	0/54 (0%)		1/53 (1.9%)
Hypoxia	0/54 (0%)		1/53 (1.9%)
Hoarseness	0/54 (0%)		6/53 (11.3%)
Sleep Apnea	1/54 (1.9%)		0/53 (0%)
Epistaxis	12/54 (22.2%)		25/53 (47.2%)
Dyspnea	28/54 (51.9%)		23/53 (43.4%)
Cough	14/54 (25.9%)		20/53 (37.7%)
Bronchospasm	0/54 (0%)		1/53 (1.9%)
Bronchopulmonary Hemorrhage	0/54 (0%)		1/53 (1.9%)
Allergic Rhinitis	4/54 (7.4%)		5/53 (9.4%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	5/54 (9.3%)		4/53 (7.5%)
Skin Ulceration	0/54 (0%)		1/53 (1.9%)
Skin Hyperpigmentation	0/54 (0%)		5/53 (9.4%)
Rash Acneiform	5/54 (9.3%)		7/53 (13.2%)
Pruritus	0/54 (0%)		4/53 (7.5%)
Periorbital Edema	0/54 (0%)		2/53 (3.8%)
Palmar-Plantar Erythrodysesthesia Syndrome	1/54 (1.9%)		2/53 (3.8%)
Pain Of Skin	1/54 (1.9%)		2/53 (3.8%)
Rash Maculo-Papular	8/54 (14.8%)		5/53 (9.4%)
Nail Ridging	1/54 (1.9%)		1/53 (1.9%)
Nail Loss	3/54 (5.6%)		3/53 (5.7%)
Nail Discoloration	2/54 (3.7%)		6/53 (11.3%)
Hyperhidrosis	0/54 (0%)		3/53 (5.7%)
Erythroderma	0/54 (0%)		1/53 (1.9%)
Erythema Multiforme	1/54 (1.9%)		1/53 (1.9%)
Dry Skin	0/54 (0%)		7/53 (13.2%)
Body Odor	1/54 (1.9%)		0/53 (0%)
Alopecia	36/54 (66.7%)		34/53 (64.2%)
Vascular disorders
Vascular Disorders - Other	0/54 (0%)		1/53 (1.9%)
Thromboembolic Event	6/54 (11.1%)		4/53 (7.5%)
Superficial Thrombophlebitis	0/54 (0%)		1/53 (1.9%)
Lymphedema	0/54 (0%)		4/53 (7.5%)
Hypotension	1/54 (1.9%)		1/53 (1.9%)
Hypertension	10/54 (18.5%)		12/53 (22.6%)
Hot Flashes	2/54 (3.7%)		7/53 (13.2%)
Hematoma	1/54 (1.9%)		1/53 (1.9%)
Flushing	1/54 (1.9%)		2/53 (3.8%)

Limitations/Caveats

The study was targeted to accrue 130 patients, but closed early for futility. Early termination leading to small numbers of subjects analyzed.

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.