Dactinomycin or Methotrexate in Treating Patients With Low-Risk Gestational Trophoblastic Neoplasia

• Sponsor: GOG Foundation (Other)
• Overall Status: Completed
• CT.gov ID: NCT01535053
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 57
• Locations: 289
• Arms: 2
• Actual Duration (Months): 97
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial studies how well methotrexate works compared to dactinomycin in treating patients with low-risk gestational trophoblastic neoplasia. Drugs used in chemotherapy, such as methotrexate and dactinomycin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether methotrexate is more effective than dactinomycin in treating gestational trophoblastic disease.

Condition or Disease	Intervention/Treatment	Phase
Choriocarcinoma; FIGO Stage I Gestational Trophoblastic Tumor; FIGO Stage II Gestational Trophoblastic Tumor; FIGO Stage III Gestational Trophoblastic Tumor; Hydatidiform Mole	Biological: Dactinomycin; Drug: Leucovorin Calcium; Drug: Methotrexate; Other: Quality-of-Life Assessment	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To test the hypothesis that treatment with multi-day methotrexate is inferior to treatment with pulse actinomycin-D (dactinomycin) in patients with low-risk gestational trophoblastic disease with respect to complete response.

SECONDARY OBJECTIVES:

1. To describe the frequency of post protocol surgical treatment for each arm. II. To describe the frequency of post protocol multi-agent chemotherapy treatment for each arm.

2. To compare multi-day methotrexate to actinomycin-D with respect to frequency and severity of adverse events in patients with low-risk gestational trophoblastic neoplasia.

3. To investigate the impact of treatment on overall quality-of-life (QOL) and explore the influence of treatment on issues such as body image, sexual functioning, and patient-reported side effects and disruption.

4. To assess whether uterine artery pulsatility index (UAPI) can provide independent prognostic information predictive of single-drug resistance.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive dactinomycin intravenously (IV) over 15 minutes on day 1.

ARM II: Patients receive methotrexate intramuscularly (IM) on days 1, 3, 5, and 7 and leucovorin calcium orally (PO) on days 2, 4, 6, and 8 OR single agent methotrexate IV on days 1-5.

In both arms, treatment repeats every 14 days for up to 20 courses* in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 1 year and then every 3 months for 1 year.

NOTE: * Patients will be treated for three courses after human chorionic gonadotropin (hCG) < 5 mIU/mL or until evidence of treatment failure (biologic progression), disease progression, or unacceptable toxicity despite dose modifications. Upon normalization of hCG (< 5 mIU/mL), patients will be treated with three additional courses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized Trial of Pulse Actinomycin-D Versus Multi-day Methotrexate for the Treatment of Low-Risk Gestational Trophoblastic Neoplasia
• Actual Study Start Date: Jun 18, 2012
• Actual Primary Completion Date: May 31, 2018
• Actual Study Completion Date: Jul 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (dactinomcin) Patients receive dactinomycin IV over 15 minutes on day 1.	Biological: Dactinomycin; Given IV; Other Names: Actinomycin A IV Actinomycin C1 Actinomycin D Actinomycin I1 Actinomycin IV Actinomycin X 1 Actinomycin-[thr-val-pro-sar-meval] Cosmegen DACT Dactinomycine Lyovac Cosmegen Meractinomycin ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment
Active Comparator: Arm II (leucovorin calcium and methotrexate) Patients receive methotrexate IM on days 1, 3, 5, and 7 and leucovorin calcium PO on days 2, 4, 6, and 8 OR single agent methotrexate IV on days 1-5.	Drug: Leucovorin Calcium; Given PO; Other Names: Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin ; Drug: Methotrexate; Given IV and IM; Other Names: Abitrexate Alpha-Methopterin Amethopterin Brimexate CL 14377 CL-14377 Emtexate Emthexat Emthexate Farmitrexat Fauldexato Folex Folex PFS Lantarel Ledertrexate Lumexon Maxtrex Medsatrexate Metex Methoblastin Methotrexate LPF Methotrexate Methylaminopterin Methotrexatum Metotrexato Metrotex Mexate Mexate-AQ MTX Novatrex Rheumatrex Texate Tremetex Trexeron Trixilem WR-19039 ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Response [hCG testing is performed prior to each cycle to treatment until treatment is completed, up to 10 months. For patients who have responded to treatment hCG must be obtained every 4 weeks for 1 year after completing treatment.]

   Complete Response is defined as 3 consecutive bi-weekly values of hCG<5 over a minimum of 4 weeks of normal hCG values with no values greater than 5 mIU/ml

Secondary Outcome Measures

1. Number of Participants With CTCAE v4 Graded Adverse Events With Low-risk Gestational Trophoblastic Neoplasia by Arm [Assessed throughout the treatment period and within 2-4 weeks after discontinuation of treatment]

   Maximum grade of physician assessed adverse events reported during treatment

2. The Number of Participants With Post Protocol Surgical Treatment for Each Arm. [Anytime during post treatment follow-up for up to 2 years from study entry.]

3. The Number of Participants With Post Protocol Multi-agent Chemotherapy Treatment for Each Arm. [Anytime during post treatment follow-up for up to 2 years from study entry.]

4. Patient-reported Quality of Life (QOL) at Baseline [Prior to cycle 1]

   Patient reported quality of life was measured with the Functional Assessment of Cancer Therapy - Generic (FACT-G). The FACT-G is a scale for assessing general QOL of cancer patients. It consists of four subscales: Physical Well Being, Functional Well Being, Social/Family Well-Being, and Emotional Well-Being. Each item in the FACT-G was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements, reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The FACT-G score is calculated as the sum of the subscale scores. The FACT-G score ranges 0-108. A larger score suggests better QOL.

5. Patient-reported Quality of Life (QOL) After Baseline Visit. [Prior to cycle 3 (4 weeks after cycle 1 if off study treatment prior to cycle 3). Prior to cycle 5, Prior to cycle 7, 26 weeks after starting study treatment.]

   Patient reported quality of life was measured with the Functional Assessment of Cancer Therapy - Generic (FACT-G). The FACT-G is a scale for assessing general QOL of cancer patients. It consists of four subscales: Physical Well Being, Functional Well Being, Social/Family Well-Being, and Emotional Well-Being. Each item in the FACT-G was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements, reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The FACT-G score is calculated as the sum of the subscale scores. The FACT-G score ranges 0-108. A larger score suggests better QOL.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients who meet International Federation of Gynecology and Obstetrics (FIGO) stage I, II, or III criteria for low-risk gestational trophoblastic neoplasia (GTN): post molar GTN or choriocarcinoma (as defined below); patients may have had a second curettage but must still meet GTN criteria below:

• Post molar GTN

• For the purposes of this study, patients must have undergone evacuation of a complete or partial hydatidiform mole and then meet the criteria for GTN defined as:

• A < 10% decrease in the hCG level using as a reference the first value in the series of 4 values taken over a period of 3 weeks (> 50 mIU/ml minimum) OR

• A > 20% sustained rise in the hCG taking as a reference the first value in the series of 3 values taken over a period of 2 weeks (> 50 mIU/ml minimum) OR

• A persistently elevated hCG level a period of 6 months or more following the initial curettage (> 50 mIU/ml minimum)

• Choriocarcinoma

• Histologically proven non-metastatic choriocarcinoma OR

• Histologically proven metastatic choriocarcinoma if the metastatic site(s) is restricted to one (or more) of the following: vagina, parametrium, or lung

• World Health Organization (WHO) risk score 0-6

• Patients must be willing to practice effective contraception for the duration of the study

• White blood cell count (WBC) >= 3,000 cells/mcL

• Granulocytes >= 1,500/mcL

• Platelets >= 100,000/mcL

• Creatinine =< 2.0 mg/dcL

• Bilirubin =< 1.5 x institutional normal

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x institutional normal

• Alkaline phosphatase =< 3 x institutional normal

• Patients who have met the pre-entry requirements

• Before enrolling a patient, the institution must verify the availability of an adequate supply of methotrexate for a full course of therapy

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

Exclusion Criteria:

• Patients who do not have GTN

• Patients with non-gestational choriocarcinoma

• Patients who have previously been treated with cytotoxic chemotherapy; however, patients who received prior low-dose methotrexate for treatment of an ectopic pregnancy will be eligible for this study

• Patients who have received prior pelvic radiation

• Patients with placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT)

• Patients with Gynecologic Oncology Group (GOG) performance status of 3 or 4

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, 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 whose circumstances at the time of study entry do not permit completion of the study or required follow-up

• Patients who wish to breast-feed during treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anchorage Associates in Radiation Medicine	Anchorage	Alaska	United States	98508
2	Anchorage Radiation Therapy Center	Anchorage	Alaska	United States	99504
3	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
4	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
5	Alaska Regional Hospital	Anchorage	Alaska	United States	99508
6	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
7	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
8	Katmai Oncology Group	Anchorage	Alaska	United States	99508
9	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
10	Cancer Center at Saint Joseph's	Phoenix	Arizona	United States	85004
11	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
12	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
13	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
14	Loma Linda University Medical Center	Loma Linda	California	United States	92354
15	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
16	Hartford Hospital	Hartford	Connecticut	United States	06102
17	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
18	Northside Hospital	Atlanta	Georgia	United States	30342
19	Augusta University Medical Center	Augusta	Georgia	United States	30912
20	Northside Hospital-Forsyth	Cumming	Georgia	United States	30041
21	Dekalb Medical Center	Decatur	Georgia	United States	30033
22	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia	United States	30501
23	Low Country Cancer Care	Savannah	Georgia	United States	31404
24	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
25	Summit Cancer Care-Memorial	Savannah	Georgia	United States	31404
26	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
27	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
28	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho	United States	83814
29	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho	United States	83619
30	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho	United States	83642
31	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho	United States	83686
32	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho	United States	83854
33	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
34	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho	United States	83301
35	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
36	Northwestern University	Chicago	Illinois	United States	60611
37	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
38	Carle on Vermilion	Danville	Illinois	United States	61832
39	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
40	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
41	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois	United States	60026
42	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois	United States	60035
43	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
44	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
45	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
46	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois	United States	60451
47	North Shore Medical Center	Skokie	Illinois	United States	60076
48	Carle Cancer Center	Urbana	Illinois	United States	61801
49	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
50	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
51	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
52	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
53	Elkhart General Hospital	Elkhart	Indiana	United States	46515
54	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
55	Community Howard Regional Health	Kokomo	Indiana	United States	46904
56	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
57	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
58	Woodland Cancer Care Center	Michigan City	Indiana	United States	46360
59	Cancer Care Partners LLC	Mishawaka	Indiana	United States	46545
60	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46545
61	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
62	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
63	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
64	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
65	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
66	South Bend Clinic	South Bend	Indiana	United States	46617
67	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
68	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
69	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
70	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
71	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
72	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky	United States	41017
73	Maine Medical Center-Bramhall Campus	Portland	Maine	United States	04102
74	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
75	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
76	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
77	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
78	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
79	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
80	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
81	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
82	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
83	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
84	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
85	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
86	Monroe Cancer Center	Monroe	Michigan	United States	48162
87	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
88	Lakeland Hospital Niles	Niles	Michigan	United States	49120
89	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
90	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
91	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
92	Munson Medical Center	Traverse City	Michigan	United States	49684
93	Metro Health Hospital	Wyoming	Michigan	United States	49519
94	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
95	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
96	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
97	Unity Hospital	Fridley	Minnesota	United States	55432
98	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
99	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
100	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
101	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
102	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
103	Health Partners Inc	Minneapolis	Minnesota	United States	55454
104	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
105	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
106	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
107	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
108	Regions Hospital	Saint Paul	Minnesota	United States	55101
109	United Hospital	Saint Paul	Minnesota	United States	55102
110	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
111	Lakeview Hospital	Stillwater	Minnesota	United States	55082
112	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
113	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
114	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
115	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
116	Cox Cancer Center Branson	Branson	Missouri	United States	65616
117	Freeman Health System	Joplin	Missouri	United States	64804
118	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
119	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
120	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
121	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
122	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
123	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
124	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
125	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
126	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
127	CoxHealth South Hospital	Springfield	Missouri	United States	65807
128	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
129	Billings Clinic Cancer Center	Billings	Montana	United States	59101
130	Saint Vincent Healthcare	Billings	Montana	United States	59101
131	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
132	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
133	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
134	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
135	Great Falls Clinic	Great Falls	Montana	United States	59405
136	Saint Peter's Community Hospital	Helena	Montana	United States	59601
137	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
138	Montana Cancer Specialists	Missoula	Montana	United States	59802
139	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
140	Community Medical Hospital	Missoula	Montana	United States	59804
141	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89106
142	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
143	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
144	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
145	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
146	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
147	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
148	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
149	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
150	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
151	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
152	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
153	Case Western Reserve University	Cleveland	Ohio	United States	44106
154	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
155	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
156	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
157	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
158	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
159	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
160	Grant Medical Center	Columbus	Ohio	United States	43215
161	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
162	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
163	Doctors Hospital	Columbus	Ohio	United States	43228
164	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
165	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
166	Grady Memorial Hospital	Delaware	Ohio	United States	43015
167	Fairfield Medical Center	Lancaster	Ohio	United States	43130
168	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
169	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
170	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
171	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
172	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
173	Licking Memorial Hospital	Newark	Ohio	United States	43055
174	Newark Radiation Oncology	Newark	Ohio	United States	43055
175	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
176	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
177	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
178	Saint Ann's Hospital	Westerville	Ohio	United States	43081
179	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
180	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
181	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
182	Saint Charles Health System	Bend	Oregon	United States	97701
183	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
184	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
185	Bay Area Hospital	Coos Bay	Oregon	United States	97420
186	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
187	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
188	Providence Portland Medical Center	Portland	Oregon	United States	97213
189	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
190	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
191	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania	United States	15009
192	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
193	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
194	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
195	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania	United States	15901
196	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania	United States	15132
197	UPMC-Coraopolis/Heritage Valley Radiation Oncology	Moon	Pennsylvania	United States	15108
198	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
199	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
200	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15213
201	UPMC-Saint Margaret	Pittsburgh	Pennsylvania	United States	15215
202	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
203	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
204	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania	United States	15236
205	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania	United States	15237
206	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania	United States	15243
207	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania	United States	16346
208	Geisinger Medical Group	State College	Pennsylvania	United States	16801
209	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania	United States	15401
210	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania	United States	15301
211	Reading Hospital	West Reading	Pennsylvania	United States	19611
212	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
213	Women and Infants Hospital	Providence	Rhode Island	United States	02905
214	Saint Francis Hospital	Greenville	South Carolina	United States	29601
215	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
216	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
217	Dell Seton Medical Center at The University of Texas	Austin	Texas	United States	78701
218	Parkland Memorial Hospital	Dallas	Texas	United States	75235
219	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
220	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
221	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
222	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington	United States	98005
223	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
224	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
225	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
226	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
227	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
228	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
229	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
230	Minor and James Medical PLLC	Seattle	Washington	United States	98104
231	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
232	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
233	Kaiser Permanente Washington	Seattle	Washington	United States	98112
234	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
235	Providence Regional Cancer System-Shelton	Shelton	Washington	United States	98584
236	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington	United States	99216
237	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington	United States	99204
238	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington	United States	99218
239	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
240	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
241	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
242	Providence Regional Cancer System-Yelm	Yelm	Washington	United States	98597
243	Monongalia Hospital	Morgantown	West Virginia	United States	26505
244	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
245	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
246	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
247	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
248	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
249	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
250	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
251	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
252	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
253	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
254	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
255	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
256	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
257	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
258	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
259	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
260	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
261	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin	United States	53188
262	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
263	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
264	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
265	Big Horn Basin Cancer Center	Cody	Wyoming	United States	82414
266	Billings Clinic-Cody	Cody	Wyoming	United States	82414
267	Welch Cancer Center	Sheridan	Wyoming	United States	82801
268	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
269	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
270	Tohoku University School of Medicine	Sendai	Aoba-ku	Japan	980-8574
271	Kure National Hospital	Kure	Hiroshima	Japan	737
272	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
273	Iwate Medical University Hospital	Shiwa-gun	Iwate	Japan	028-3695
274	Kagoshima City Hospital	Kagoshima City	Kagoshima	Japan	890-8760
275	Niigata University Medical and Dental Hospital	Niigata City	Niigata	Japan	951-8520
276	University of the Ryukyus Hospital-Col Health Scnc	Nakagami-gun	Okinawa	Japan	903-0215
277	Hiroshima University Hospital	Hiroshima City		Japan	734-8551
278	Kindai University	Osaka		Japan	589 8511
279	Saitama Medical University International Medical Center	Saitama		Japan	350-1298
280	Tottori University	Tottori		Japan	680-8550
281	Samsung Medical Center	Seoul	Korea	Korea, Republic of	135-710
282	Catholic University of Korea-Seoul Saint Mary's Hospital	Seoul	Korea	Korea, Republic of	137-040
283	Seoul National University Bundang Hospital	Seongnam City	Kyeonggi-do	Korea, Republic of	463-707
284	Gachon University Gil Hospital	Incheon		Korea, Republic of	405-760
285	Asan Medical Center	Seoul		Korea, Republic of	05505
286	Gangnam Severance Hospital	Seoul		Korea, Republic of	06273
287	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
288	Korea Cancer Center Hospital	Seoul		Korea, Republic of	139-706
289	Weston Park Hospital	Sheffield	England	United Kingdom	S10 2SJ

Sponsors and Collaborators

• GOG Foundation
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Julian C Schink, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 25, 2015

More Information

Publications

None provided.

• Responsible Party: GOG Foundation
• ClinicalTrials.gov Identifier: NCT01535053
• Other Study ID Numbers: GOG-0275; NCI-2012-00250; CDR0000725211; PGOG-0275_A08PAMDREVW01; GOG-0275; GOG-0275; GOG-0275; U10CA180868; U10CA027469
• First Posted: Feb 17, 2012
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Additional relevant MeSH terms: Choriocarcinoma; Trophoblastic Neoplasms; Gestational Trophoblastic Disease; Hydatidiform Mole; Calcium, Dietary; Leucovorin; Folic Acid; Dactinomycin; Methotrexate; Calcium; Levoleucovorin

Study Results

Participant Flow

Recruitment Details	The study was activated on 6/18/2012and closed to accrual prematurely on 9/20/2016 by the sponsor due to slow accrual.
Pre-assignment Detail	Sites declared in advance which of 2 methotrexate regimens they would follow for patients who received a random treatment allocation to the methotrexate arm. Randomization is stratified by country (US, Canada, Japan, Korea, Australia, United Kingdom, etc.) and Multi-day methotrexate regimen (8- or 5-day) used by the participating site.

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
Period Title: Overall Study
STARTED	29	28
COMPLETED	28	26
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)	Total
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.	Total of all reporting groups
Overall Participants	28	26	54
Age, Customized (Count of Participants)
10-19 years	1 3.6%	1 3.8%	2 3.7%
20-29 years	14 50%	11 42.3%	25 46.3%
30-39 years	11 39.3%	11 42.3%	22 40.7%
40-49 years	2 7.1%	3 11.5%	5 9.3%
Sex: Female, Male (Count of Participants)
Female	28 100%	26 100%	54 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	26 92.9%	24 92.3%	50 92.6%
Not Hispanic or Latino	2 7.1%	2 7.7%	4 7.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	6 21.4%	6 23.1%	12 22.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 21.4%	1 3.8%	7 13%
White	16 57.1%	19 73.1%	35 64.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response
Description	Complete Response is defined as 3 consecutive bi-weekly values of hCG<5 over a minimum of 4 weeks of normal hCG values with no values greater than 5 mIU/ml
Time Frame	hCG testing is performed prior to each cycle to treatment until treatment is completed, up to 10 months. For patients who have responded to treatment hCG must be obtained every 4 weeks for 1 year after completing treatment.

Outcome Measure Data

Analysis Population Description

Eligible patients

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
Measure Participants	28	26
Number (95% Confidence Interval) [percentage of participants]	78.6 280.7%	88.5 340.4%

2. Secondary Outcome

Title	Number of Participants With CTCAE v4 Graded Adverse Events With Low-risk Gestational Trophoblastic Neoplasia by Arm
Description	Maximum grade of physician assessed adverse events reported during treatment
Time Frame	Assessed throughout the treatment period and within 2-4 weeks after discontinuation of treatment

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
Measure Participants	28	26
Grade 1	7 25%	4 15.4%
Grade 2	14 50%	10 38.5%
Grade 3	6 21.4%	10 38.5%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%

3. Secondary Outcome

Title	The Number of Participants With Post Protocol Surgical Treatment for Each Arm.
Time Frame	Anytime during post treatment follow-up for up to 2 years from study entry.

Outcome Measure Data

Analysis Population Description

Non-responding eligible patients in follow-up

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
Measure Participants	7	5
Number [participants]	0 0%	0 0%

4. Secondary Outcome

Title	The Number of Participants With Post Protocol Multi-agent Chemotherapy Treatment for Each Arm.
Time Frame	Anytime during post treatment follow-up for up to 2 years from study entry.

Outcome Measure Data

Analysis Population Description

Non-responding eligible patients in follow-up

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
Measure Participants	7	5
Number [participants]	0 0%	0 0%

5. Secondary Outcome

Title	Patient-reported Quality of Life (QOL) at Baseline
Description	Patient reported quality of life was measured with the Functional Assessment of Cancer Therapy - Generic (FACT-G). The FACT-G is a scale for assessing general QOL of cancer patients. It consists of four subscales: Physical Well Being, Functional Well Being, Social/Family Well-Being, and Emotional Well-Being. Each item in the FACT-G was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements, reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The FACT-G score is calculated as the sum of the subscale scores. The FACT-G score ranges 0-108. A larger score suggests better QOL.
Time Frame	Prior to cycle 1

Outcome Measure Data

Analysis Population Description

Provided baseline QOL questionnaire

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
Measure Participants	27	27
Mean (Standard Error) [units on a scale]	82.3 (2.7)	81.9 (3.3)

6. Secondary Outcome

Title	Patient-reported Quality of Life (QOL) After Baseline Visit.
Description	Patient reported quality of life was measured with the Functional Assessment of Cancer Therapy - Generic (FACT-G). The FACT-G is a scale for assessing general QOL of cancer patients. It consists of four subscales: Physical Well Being, Functional Well Being, Social/Family Well-Being, and Emotional Well-Being. Each item in the FACT-G was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements, reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The FACT-G score is calculated as the sum of the subscale scores. The FACT-G score ranges 0-108. A larger score suggests better QOL.
Time Frame	Prior to cycle 3 (4 weeks after cycle 1 if off study treatment prior to cycle 3). Prior to cycle 5, Prior to cycle 7, 26 weeks after starting study treatment.

Outcome Measure Data

Analysis Population Description

Provided baseline and ≥1 follow-up assessments

Arm/Group Title	Regimen I (Dactinomycin)	Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)	institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
Measure Participants	27	27
Pre-cycle 3	78.3 (2.3)	81.6 (2.7)
Pre-cycle 5	75.5 (3.3)	78.9 (2.8)
Pre-cycle 7	85.0 (2.7)	84.5 (2.2)
26 weeks	91.2 (2.9)	90.9 (2.9)

Adverse Events

Time Frame	Through Study Treatment and up to 30 days after discontinuing treatment.
Adverse Event Reporting Description	Participants listed in the all-cause mortality include all enrolled. Participants in the Serious Adverse Event and Other Adverse Events include all eligible AND treated. Therefore, the number of participants listed in the all-cause mortality is larger than the serious adverse event and other adverse event tables.
Arm/Group Title	Regimen I (Dactinomycin)		Regimen II (Methotrexate)
Arm/Group Description	IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)		institutional preference of either: IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.
All Cause Mortality
	Regimen I (Dactinomycin)		Regimen II (Methotrexate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/28 (0%)
Serious Adverse Events
	Regimen I (Dactinomycin)		Regimen II (Methotrexate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/28 (3.6%)		1/26 (3.8%)
Infections and infestations
Appendicitis	0/28 (0%)		1/26 (3.8%)
Psychiatric disorders
Psychiatric Disorders - Other	1/28 (3.6%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Regimen I (Dactinomycin)		Regimen II (Methotrexate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/28 (96.4%)		24/26 (92.3%)
Blood and lymphatic system disorders
Lymph Node Pain	0/28 (0%)		1/26 (3.8%)
Blood And Lymphatic System Disorders - Other	1/28 (3.6%)		3/26 (11.5%)
Anemia	13/28 (46.4%)		15/26 (57.7%)
Cardiac disorders
Palpitations	1/28 (3.6%)		1/26 (3.8%)
Cardiac Disorders - Other	0/28 (0%)		1/26 (3.8%)
Ear and labyrinth disorders
Tinnitus	1/28 (3.6%)		4/26 (15.4%)
Hearing Impaired	0/28 (0%)		1/26 (3.8%)
Ear Pain	2/28 (7.1%)		0/26 (0%)
Eye disorders
Eye Disorders - Other	0/28 (0%)		3/26 (11.5%)
Watering Eyes	0/28 (0%)		4/26 (15.4%)
Eye Pain	1/28 (3.6%)		0/26 (0%)
Photophobia	0/28 (0%)		1/26 (3.8%)
Blurred Vision	4/28 (14.3%)		3/26 (11.5%)
Dry Eye	0/28 (0%)		4/26 (15.4%)
Gastrointestinal disorders
Dysphagia	1/28 (3.6%)		3/26 (11.5%)
Dyspepsia	0/28 (0%)		1/26 (3.8%)
Constipation	12/28 (42.9%)		11/26 (42.3%)
Diarrhea	7/28 (25%)		7/26 (26.9%)
Vomiting	8/28 (28.6%)		6/26 (23.1%)
Stomach Pain	0/28 (0%)		2/26 (7.7%)
Abdominal Pain	10/28 (35.7%)		6/26 (23.1%)
Oral Dysesthesia	1/28 (3.6%)		0/26 (0%)
Mucositis Oral	12/28 (42.9%)		20/26 (76.9%)
Gastrointestinal Disorders - Other	0/28 (0%)		1/26 (3.8%)
Gingival Pain	1/28 (3.6%)		1/26 (3.8%)
Nausea	20/28 (71.4%)		16/26 (61.5%)
Gastroesophageal Reflux Disease	3/28 (10.7%)		1/26 (3.8%)
General disorders
General Disorders And Administration Site Conditio	3/28 (10.7%)		0/26 (0%)
Pain	0/28 (0%)		2/26 (7.7%)
Malaise	3/28 (10.7%)		1/26 (3.8%)
Localized Edema	0/28 (0%)		1/26 (3.8%)
Flu Like Symptoms	1/28 (3.6%)		2/26 (7.7%)
Non-Cardiac Chest Pain	1/28 (3.6%)		0/26 (0%)
Edema Limbs	1/28 (3.6%)		0/26 (0%)
Edema Face	0/28 (0%)		1/26 (3.8%)
Fatigue	18/28 (64.3%)		15/26 (57.7%)
Fever	2/28 (7.1%)		1/26 (3.8%)
Chills	1/28 (3.6%)		1/26 (3.8%)
Immune system disorders
Allergic Reaction	0/28 (0%)		1/26 (3.8%)
Infections and infestations
Infections And Infestations - Other	4/28 (14.3%)		1/26 (3.8%)
Upper Respiratory Infection	0/28 (0%)		1/26 (3.8%)
Vulval Infection	0/28 (0%)		1/26 (3.8%)
Skin Infection	1/28 (3.6%)		2/26 (7.7%)
Pharyngitis	0/28 (0%)		1/26 (3.8%)
Vaginal Infection	0/28 (0%)		2/26 (7.7%)
Urinary Tract Infection	1/28 (3.6%)		1/26 (3.8%)
Injury, poisoning and procedural complications
Bruising	1/28 (3.6%)		0/26 (0%)
Investigations
Investigations - Other	1/28 (3.6%)		0/26 (0%)
Weight Gain	0/28 (0%)		2/26 (7.7%)
Platelet Count Decreased	3/28 (10.7%)		4/26 (15.4%)
Hemoglobin Increased	1/28 (3.6%)		0/26 (0%)
Ggt Increased	1/28 (3.6%)		1/26 (3.8%)
Neutrophil Count Decreased	5/28 (17.9%)		7/26 (26.9%)
White Blood Cell Decreased	4/28 (14.3%)		6/26 (23.1%)
Aspartate Aminotransferase Increased	2/28 (7.1%)		1/26 (3.8%)
Alkaline Phosphatase Increased	1/28 (3.6%)		0/26 (0%)
Alanine Aminotransferase Increased	2/28 (7.1%)		1/26 (3.8%)
Metabolism and nutrition disorders
Hypophosphatemia	0/28 (0%)		2/26 (7.7%)
Hyponatremia	1/28 (3.6%)		0/26 (0%)
Hypokalemia	2/28 (7.1%)		0/26 (0%)
Hypoglycemia	3/28 (10.7%)		0/26 (0%)
Hypocalcemia	1/28 (3.6%)		2/26 (7.7%)
Hypoalbuminemia	1/28 (3.6%)		2/26 (7.7%)
Hyperglycemia	4/28 (14.3%)		1/26 (3.8%)
Anorexia	4/28 (14.3%)		7/26 (26.9%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	1/28 (3.6%)		1/26 (3.8%)
Myalgia	3/28 (10.7%)		1/26 (3.8%)
Generalized Muscle Weakness	2/28 (7.1%)		0/26 (0%)
Back Pain	2/28 (7.1%)		1/26 (3.8%)
Arthralgia	1/28 (3.6%)		0/26 (0%)
Musculoskeletal And Connective Tissue Disorder - O	0/28 (0%)		1/26 (3.8%)
Nervous system disorders
Peripheral Sensory Neuropathy	1/28 (3.6%)		0/26 (0%)
Peripheral Motor Neuropathy	1/28 (3.6%)		0/26 (0%)
Paresthesia	1/28 (3.6%)		1/26 (3.8%)
Headache	8/28 (28.6%)		5/26 (19.2%)
Facial Muscle Weakness	1/28 (3.6%)		0/26 (0%)
Dysgeusia	1/28 (3.6%)		0/26 (0%)
Syncope	1/28 (3.6%)		0/26 (0%)
Dizziness	2/28 (7.1%)		0/26 (0%)
Psychiatric disorders
Psychiatric Disorders - Other	1/28 (3.6%)		0/26 (0%)
Suicidal Ideation	0/28 (0%)		1/26 (3.8%)
Personality Change	1/28 (3.6%)		0/26 (0%)
Insomnia	1/28 (3.6%)		6/26 (23.1%)
Depression	1/28 (3.6%)		1/26 (3.8%)
Confusion	0/28 (0%)		1/26 (3.8%)
Anxiety	2/28 (7.1%)		2/26 (7.7%)
Renal and urinary disorders
Urinary Retention	1/28 (3.6%)		0/26 (0%)
Urinary Tract Pain	1/28 (3.6%)		0/26 (0%)
Urinary Frequency	1/28 (3.6%)		0/26 (0%)
Proteinuria	0/28 (0%)		1/26 (3.8%)
Hematuria	1/28 (3.6%)		3/26 (11.5%)
Reproductive system and breast disorders
Reproductive System And Breast Disorders - Other	1/28 (3.6%)		0/26 (0%)
Vaginal Hemorrhage	6/28 (21.4%)		7/26 (26.9%)
Vaginal Dryness	0/28 (0%)		1/26 (3.8%)
Perineal Pain	1/28 (3.6%)		0/26 (0%)
Pelvic Pain	1/28 (3.6%)		1/26 (3.8%)
Menorrhagia	2/28 (7.1%)		0/26 (0%)
Irregular Menstruation	1/28 (3.6%)		0/26 (0%)
Vaginal Discharge	5/28 (17.9%)		3/26 (11.5%)
Vaginal Inflammation	0/28 (0%)		1/26 (3.8%)
Respiratory, thoracic and mediastinal disorders
Sore Throat	1/28 (3.6%)		0/26 (0%)
Sneezing	1/28 (3.6%)		0/26 (0%)
Pleuritic Pain	0/28 (0%)		3/26 (11.5%)
Dyspnea	5/28 (17.9%)		4/26 (15.4%)
Cough	4/28 (14.3%)		2/26 (7.7%)
Allergic Rhinitis	1/28 (3.6%)		1/26 (3.8%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	2/28 (7.1%)		2/26 (7.7%)
Urticaria	1/28 (3.6%)		0/26 (0%)
Skin Ulceration	0/28 (0%)		1/26 (3.8%)
Skin Hyperpigmentation	1/28 (3.6%)		0/26 (0%)
Rash Acneiform	2/28 (7.1%)		1/26 (3.8%)
Pruritus	0/28 (0%)		3/26 (11.5%)
Photosensitivity	1/28 (3.6%)		1/26 (3.8%)
Rash Maculo-Papular	3/28 (10.7%)		3/26 (11.5%)
Dry Skin	1/28 (3.6%)		3/26 (11.5%)
Alopecia	7/28 (25%)		5/26 (19.2%)
Vascular disorders
Thromboembolic Event	1/28 (3.6%)		0/26 (0%)
Phlebitis	1/28 (3.6%)		0/26 (0%)
Hypotension	0/28 (0%)		1/26 (3.8%)
Hypertension	1/28 (3.6%)		1/26 (3.8%)
Hot Flashes	3/28 (10.7%)		1/26 (3.8%)
Flushing	0/28 (0%)		2/26 (7.7%)

Limitations/Caveats

Early closure leading to non-compliance and small numbers of subjects analyzed. Study cannot be considered terminated because some participants are still being examined for follow-up.

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.