Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

• Sponsor: GOG Foundation (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01042522
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 63
• Locations: 219
• Arms: 2
• Anticipated Duration (Months): 152.8
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies paclitaxel and carboplatin to see how well they work compared with bleomycin sulfate, etoposide phosphate, and cisplatin in treating patients with sex cord-ovarian stromal tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or has returned (recurrent). Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective in treating sex cord-ovarian stromal tumors.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor, Not Otherwise Specified; Ovarian Steroid Cell Tumor	Biological: Bleomycin Sulfate; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide Phosphate; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the activity of paclitaxel and carboplatin with respect to progression free survival (using bleomycin, etoposide, and cisplatin [BEP] as a reference) for newly diagnosed advanced or recurrent chemonaive ovarian sex cord-stromal tumors.

SECONDARY OBJECTIVES:

1. To estimate the toxicity of paclitaxel and carboplatin, and bleomycin, etoposide, and cisplatin in this patient population.

2. To estimate overall survival for paclitaxel and carboplatin relative to that of BEP.

3. To evaluate response rate in the subset of patients with measurable disease.

TERTIARY OBJECTIVES:

1. To collect fixed and/or frozen tumor tissue for future translational research studies.

2. To explore the utility of inhibin A and inhibin B as prognostic and predictive biomarkers for ovarian sex cord-stromal tumors and to examine changes in these markers with treatment.

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

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bleomycin sulfate IV on day 1 and etoposide phosphate* IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients who have received prior radiotherapy receive etoposide phosphate on days 1-4.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Paclitaxel and Carboplatin vs. Bleomycin, Etoposide, and Cisplatin for Newly Diagnosed Advanced Stage and Recurrent Chemonaive Sex Cord-Stromal Tumors of the Ovary
• Actual Study Start Date: Feb 8, 2010
• Actual Primary Completion Date: Jun 12, 2020
• Anticipated Study Completion Date: Nov 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (paclitaxel, carboplatin) Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat
Experimental: Arm II (bleomycin sulfate, etoposide phosphate, cisplatin) Patients receive bleomycin sulfate IV on day 1 and etoposide IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Biological: Bleomycin Sulfate; Given IV; Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Bleomycini Sulfas Blexane Oil Bleo ; Drug: Cisplatin; Given IV; Other Names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin ; Drug: Etoposide Phosphate; Given IV; Other Names: Etopophos ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [From start of treatment to time of progression or death, whichever occurs first. Median follow-up time was 48 months.]

   The relationship of randomized treatment to progression free survival. The RECIST 1.1 criteria are used for disease progression. This is the criteria: progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

Secondary Outcome Measures

1. Tumor Response Rate [Median followup time was 48 months.]

   Proportion of evaluable patients with complete or partial tumor response by RECIST 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (ORR = CR + PR).

2. Overall Survival (OS) [From start of treatment to time of death or the date of last contact, assessed up to 10 years. Median follow-up time was 48 months.]

   The relationship of treatment to overall survival will be assessed. The number of death events in the treatment arm is reported.

Other Outcome Measures

1. Change in Inhibin A and Inhibin B Levels [Baseline to up to 2 years]

   Pre-treatment levels of inhibin A and inhibin B will be examined in relation to OS and PFS in Cox proportional hazards models. Changes from baseline in inhibin levels will be compared between treatment groups using mixed effects models accounting for the longitudinal nature of the data. The repeated measures of inhibin will also be explored versus overall survival and PFS using time-dependent covariates in Cox proportional hazards models.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with histologically confirmed ovarian stromal tumor [granulosa cell tumor, ganulosa cell-theca cell tumor, Sertoli-Leydig cell tumor (androblastoma), steroid (lipid) cell tumor, gynandroblastoma, unclassified sex cord-stromal tumor, sex cord tumor with annular tubules]

• Patients must have newly diagnosed, stage IIA - IV disease and must be entered within eight weeks from surgery; they may have either measurable residual disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, or they may have no measurable residual disease; OR, they must have biopsy-proven recurrent disease of any stage and have never received cytotoxic chemotherapy

• Patients must have a Gynecologic Oncology Group (GOG) performance grade of 0, 1, or 2

• Patients of childbearing potential must have a negative serum pregnancy test and must agree to practice an effective means of birth control

• Patients in the measureable disease cohort 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

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to Common Terminology Criteria for Adverse Events (CTCAE) grade 1

• Platelet greater than or equal to 100,000/mcl

• Creatinine no greater than the institutional upper limits of normal

• Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (CTCAE grade 1)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3.0 x ULN (CTCAE grade 1)

• Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE grade 1)

• Neuropathy (sensory and motor) less than or equal to CTCAE grade 1

• No signs of clinically significant hearing loss

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

• Patients must have pulmonary function sufficient to receive bleomycin, with normal lung expansion, absence of crackles on auscultation, and normal carbon monoxide diffusion (DLCO), defined as greater than 80% predicted

• Patients with a history of hypersensitivity reactions to prior chemotherapy administered for previous cancer diagnoses are eligible to participate in the study, unless the hypersensitivity reaction consisted of anaphylaxis not amenable to desensitization

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

• Patients must be entered within 8 weeks after surgery performed for either 1) initial diagnosis, staging, and/or cytoreduction, or 2) (if done) management of recurrent disease in a chemonaive patient

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

Exclusion Criteria:

• Patients who have received any prior cytotoxic chemotherapy or biologics for sex cord-stromal tumors (SCSTs)

• Patients with apparent stage I disease who have not undergone a staging procedure

• 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

• Woman who are pregnant or breastfeeding

• Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator can consult the study chair or study co-chairs for uncertainty in this regard

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
2	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
3	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
4	Katmai Oncology Group	Anchorage	Alaska	United States	99508
5	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
6	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
7	Olive View-University of California Los Angeles Medical Center	Sylmar	California	United States	91342
8	University of Colorado Hospital	Aurora	Colorado	United States	80045
9	Hartford Hospital	Hartford	Connecticut	United States	06102
10	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
11	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
12	Northside Hospital	Atlanta	Georgia	United States	30342
13	Augusta University Medical Center	Augusta	Georgia	United States	30912
14	Northside Hospital-Forsyth	Cumming	Georgia	United States	30041
15	Central Georgia Gynecologic Oncology	Macon	Georgia	United States	31201
16	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
17	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
18	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho	United States	83814
19	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho	United States	83854
20	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
21	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
22	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
23	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
24	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
25	SIH Cancer Institute	Carterville	Illinois	United States	62918
26	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
27	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
28	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
29	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
30	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
31	Crossroads Cancer Center	Effingham	Illinois	United States	62401
32	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
33	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
34	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
35	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
36	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois	United States	60026
37	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois	United States	60035
38	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
39	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
40	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
41	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
42	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois	United States	60451
43	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
44	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
45	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
46	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
47	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
48	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
49	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
50	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
51	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
52	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
53	Valley Radiation Oncology	Peru	Illinois	United States	61354
54	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
55	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
56	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
57	Springfield Clinic	Springfield	Illinois	United States	62702
58	Memorial Medical Center	Springfield	Illinois	United States	62781
59	Southwest Illinois Health Services LLP	Swansea	Illinois	United States	62226
60	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
61	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
62	Coffeyville Regional Medical Center	Coffeyville	Kansas	United States	67337
63	University of Kansas Clinical Research Center	Fairway	Kansas	United States	66205
64	HaysMed University of Kansas Health System	Hays	Kansas	United States	67601
65	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
66	Olathe Health Cancer Center	Olathe	Kansas	United States	66061
67	Ascension Via Christi - Pittsburg	Pittsburg	Kansas	United States	66762
68	Salina Regional Health Center	Salina	Kansas	United States	67401
69	University of Kansas Health System Saint Francis Campus	Topeka	Kansas	United States	66606
70	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas	United States	66205
71	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
72	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
73	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
74	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
75	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
76	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
77	Henry Ford Hospital	Detroit	Michigan	United States	48202
78	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
79	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
80	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
81	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
82	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
83	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
84	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
85	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
86	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
87	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
88	Cox Cancer Center Branson	Branson	Missouri	United States	65616
89	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
90	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
91	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
92	Freeman Health System	Joplin	Missouri	United States	64804
93	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
94	Truman Medical Centers	Kansas City	Missouri	United States	64108
95	University of Kansas Cancer Center - North	Kansas City	Missouri	United States	64154
96	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri	United States	64116
97	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
98	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
99	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
100	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
101	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
102	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
103	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
104	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
105	CoxHealth South Hospital	Springfield	Missouri	United States	65807
106	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
107	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
108	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
109	Billings Clinic Cancer Center	Billings	Montana	United States	59101
110	Saint Vincent Healthcare	Billings	Montana	United States	59101
111	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
112	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
113	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
114	Great Falls Clinic	Great Falls	Montana	United States	59405
115	Saint Peter's Community Hospital	Helena	Montana	United States	59601
116	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
117	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
118	Community Medical Hospital	Missoula	Montana	United States	59804
119	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
120	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
121	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
122	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
123	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
124	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
125	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
126	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
127	Memorial Sloan Kettering Sleepy Hollow	Sleepy Hollow	New York	United States	10591
128	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
129	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
130	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
131	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
132	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina	United States	28025
133	Duke University Medical Center	Durham	North Carolina	United States	27710
134	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
135	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
136	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
137	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
138	Case Western Reserve University	Cleveland	Ohio	United States	44106
139	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
140	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
141	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
142	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
143	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
144	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
145	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
146	Grant Medical Center	Columbus	Ohio	United States	43215
147	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
148	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
149	Doctors Hospital	Columbus	Ohio	United States	43228
150	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
151	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
152	Grady Memorial Hospital	Delaware	Ohio	United States	43015
153	Dublin Methodist Hospital	Dublin	Ohio	United States	43016
154	Central Ohio Breast and Endocrine Surgery	Gahanna	Ohio	United States	43230
155	Mount Carmel Grove City Hospital	Grove City	Ohio	United States	43123
156	Fairfield Medical Center	Lancaster	Ohio	United States	43130
157	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
158	OhioHealth Mansfield Hospital	Mansfield	Ohio	United States	44903
159	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
160	OhioHealth Marion General Hospital	Marion	Ohio	United States	43302
161	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
162	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
163	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
164	Licking Memorial Hospital	Newark	Ohio	United States	43055
165	Newark Radiation Oncology	Newark	Ohio	United States	43055
166	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
167	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
168	Saint Ann's Hospital	Westerville	Ohio	United States	43081
169	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
170	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
171	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
172	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
173	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
174	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
175	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
176	Providence Portland Medical Center	Portland	Oregon	United States	97213
177	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
178	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
179	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
180	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
181	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
182	Jefferson Hospital	Jefferson Hills	Pennsylvania	United States	15025
183	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
184	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
185	Forbes Hospital	Monroeville	Pennsylvania	United States	15146
186	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
187	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
188	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
189	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
190	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania	United States	17901
191	Community Medical Center	Scranton	Pennsylvania	United States	18510
192	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania	United States	17870
193	Geisinger Medical Group	State College	Pennsylvania	United States	16801
194	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania	United States	15090
195	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
196	Women and Infants Hospital	Providence	Rhode Island	United States	02905
197	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
198	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
199	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
200	Parkland Memorial Hospital	Dallas	Texas	United States	75235
201	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
202	M D Anderson Cancer Center	Houston	Texas	United States	77030
203	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
204	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
205	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
206	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
207	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
208	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
209	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
210	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
211	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
212	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
213	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
214	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495
215	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
216	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
217	Big Horn Basin Cancer Center	Cody	Wyoming	United States	82414
218	Billings Clinic-Cody	Cody	Wyoming	United States	82414
219	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• GOG Foundation
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jubilee Brown, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 13, 2016

More Information

Publications

None provided.

• Responsible Party: GOG Foundation
• ClinicalTrials.gov Identifier: NCT01042522
• Other Study ID Numbers: GOG-0264; NCI-2011-02000; CDR0000662814; GOG-0264; GOG-0264; U10CA180868; U10CA027469
• First Posted: Jan 5, 2010
• Last Update Posted: Jan 25, 2022
• Last Verified: Dec 1, 2021

• Additional relevant MeSH terms: Neoplasms; Sex Cord-Gonadal Stromal Tumors; Granulosa Cell Tumor; Leydig Cell Tumor; Sertoli-Leydig Cell Tumor; Paclitaxel; Etoposide; Cisplatin; Carboplatin; Albumin-Bound Paclitaxel; Bleomycin; Etoposide phosphate

Study Results

Participant Flow

Arm/Group Title	Arm I (Paclitaxel, Carboplatin)	Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV	Patients receive bleomycin sulfate IV on day 1 and etoposide IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Bleomycin Sulfate: Given IV Cisplatin: Given IV Etoposide Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	31	32
COMPLETED	23	26
NOT COMPLETED	8	6

Baseline Characteristics

Arm/Group Title	Arm I (Paclitaxel, Carboplatin)	Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)	Total
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV	Patients receive bleomycin sulfate IV on day 1 and etoposide IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Bleomycin Sulfate: Given IV Cisplatin: Given IV Etoposide Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies	Total of all reporting groups
Overall Participants	31	32	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.71 (12.51)	44.05 (13.86)	47.33 (13.53)
Age, Customized (Count of Participants)
20 - 29 years	2 6.5%	7 21.9%	9 14.3%
30 - 39 years	2 6.5%	5 15.6%	7 11.1%
40 - 49 years	13 41.9%	6 18.8%	19 30.2%
50 - 59 years	6 19.4%	10 31.3%	16 25.4%
>= 60 years	8 25.8%	4 12.5%	12 19%
Sex: Female, Male (Count of Participants)
Female	31 100%	32 100%	63 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 9.7%	8 25%	11 17.5%
Not Hispanic or Latino	27 87.1%	23 71.9%	50 79.4%
Unknown or Not Reported	1 3.2%	1 3.1%	2 3.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.2%	1 3.1%	2 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 19.4%	5 15.6%	11 17.5%
White	23 74.2%	25 78.1%	48 76.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.2%	1 3.1%	2 3.2%
Performance Status (Count of Participants)
0	21 67.7%	28 87.5%	49 77.8%
1	9 29%	4 12.5%	13 20.6%
2	1 3.2%	0 0%	1 1.6%
Measurable Disease (Count of Participants)
Measurable Disease	11 35.5%	12 37.5%	23 36.5%
No Measurable Disease	20 64.5%	20 62.5%	40 63.5%
Cell Type (Count of Participants)
Lipid Cell Tumor	1 3.2%	0 0%	1 1.6%
Granulosa Cell Tumor	28 90.3%	27 84.4%	55 87.3%
Sex Cord Stromal Tumor, Unclassified	2 6.5%	2 6.3%	4 6.3%
Sertoli-leydig Cell Tumor	0 0%	3 9.4%	3 4.8%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	The relationship of randomized treatment to progression free survival. The RECIST 1.1 criteria are used for disease progression. This is the criteria: progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time Frame	From start of treatment to time of progression or death, whichever occurs first. Median follow-up time was 48 months.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Arm I (Paclitaxel, Carboplatin)	Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV	Patients receive bleomycin sulfate IV on day 1 and etoposide IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Bleomycin Sulfate: Given IV Cisplatin: Given IV Etoposide Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	31	32
Median (95% Confidence Interval) [months]	27.7	19.7

2. Secondary Outcome

Title	Tumor Response Rate
Description	Proportion of evaluable patients with complete or partial tumor response by RECIST 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (ORR = CR + PR).
Time Frame	Median followup time was 48 months.

Outcome Measure Data

Analysis Population Description

Patients with at least one target lesion by RECIST 1.1 criteria and and at least one CT tumor assessment

Arm/Group Title	Arm I (Paclitaxel, Carboplatin)	Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV	Patients receive bleomycin sulfate IV on day 1 and etoposide IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Bleomycin Sulfate: Given IV Cisplatin: Given IV Etoposide Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	14	13
Number (95% Confidence Interval) [proportion of participants]	0.43 1.4%	0.54 1.7%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	The relationship of treatment to overall survival will be assessed. The number of death events in the treatment arm is reported.
Time Frame	From start of treatment to time of death or the date of last contact, assessed up to 10 years. Median follow-up time was 48 months.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Arm I (Paclitaxel, Carboplatin)	Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV	Patients receive bleomycin sulfate IV on day 1 and etoposide IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Bleomycin Sulfate: Given IV Cisplatin: Given IV Etoposide Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	31	32
Count of Participants [Participants]	5 16.1%	8 25%

4. Other Pre-specified Outcome

Title	Change in Inhibin A and Inhibin B Levels
Description	Pre-treatment levels of inhibin A and inhibin B will be examined in relation to OS and PFS in Cox proportional hazards models. Changes from baseline in inhibin levels will be compared between treatment groups using mixed effects models accounting for the longitudinal nature of the data. The repeated measures of inhibin will also be explored versus overall survival and PFS using time-dependent covariates in Cox proportional hazards models.
Time Frame	Baseline to up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	The adverse events were assessed during the treatment period and up to 100 days after stopping study treatment (an average of 33 months).
Arm/Group Title	Arm I (Paclitaxel, Carboplatin)		Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Paclitaxel: Given IV		Patients receive bleomycin sulfate IV on day 1 and etoposide IV over 1 hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Bleomycin Sulfate: Given IV Cisplatin: Given IV Etoposide Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Arm I (Paclitaxel, Carboplatin)		Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/31 (16.1%)		8/32 (25%)
Serious Adverse Events
	Arm I (Paclitaxel, Carboplatin)		Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/31 (19.4%)		11/32 (34.4%)
Blood and lymphatic system disorders
Anemia	1/31 (3.2%)		0/32 (0%)
Febrile Neutropenia	0/31 (0%)		2/32 (6.3%)
Cardiac disorders
Sinus Bradycardia	0/31 (0%)		1/32 (3.1%)
Gastrointestinal disorders
Ileus	0/31 (0%)		1/32 (3.1%)
General disorders
Pain	1/31 (3.2%)		0/32 (0%)
Death Nos	1/31 (3.2%)		0/32 (0%)
Investigations
Neutrophil Count Decreased	5/31 (16.1%)		7/32 (21.9%)
Metabolism and nutrition disorders
Hyperglycemia	0/31 (0%)		1/32 (3.1%)
Nervous system disorders
Syncope	0/31 (0%)		1/32 (3.1%)
Vascular disorders
Thromboembolic Event	0/31 (0%)		1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	Arm I (Paclitaxel, Carboplatin)		Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/31 (100%)		29/32 (90.6%)
Blood and lymphatic system disorders
Leukocytosis	0/31 (0%)		2/32 (6.3%)
Blood And Lymphatic System Disorders - Other	3/31 (9.7%)		2/32 (6.3%)
Anemia	26/31 (83.9%)		26/32 (81.3%)
Cardiac disorders
Atrial Fibrillation	0/31 (0%)		1/32 (3.1%)
Sinus Bradycardia	0/31 (0%)		1/32 (3.1%)
Palpitations	1/31 (3.2%)		4/32 (12.5%)
Cardiac Disorders - Other	1/31 (3.2%)		0/32 (0%)
Sinus Tachycardia	1/31 (3.2%)		2/32 (6.3%)
Ear and labyrinth disorders
Tinnitus	3/31 (9.7%)		11/32 (34.4%)
Ear Pain	1/31 (3.2%)		1/32 (3.1%)
Endocrine disorders
Hypothyroidism	1/31 (3.2%)		1/32 (3.1%)
Hyperthyroidism	0/31 (0%)		1/32 (3.1%)
Endocrine Disorders - Other	0/31 (0%)		1/32 (3.1%)
Eye disorders
Eye Disorders - Other	2/31 (6.5%)		0/32 (0%)
Watering Eyes	0/31 (0%)		1/32 (3.1%)
Blurred Vision	3/31 (9.7%)		5/32 (15.6%)
Gastrointestinal disorders
Dyspepsia	2/31 (6.5%)		8/32 (25%)
Constipation	18/31 (58.1%)		11/32 (34.4%)
Diarrhea	7/31 (22.6%)		9/32 (28.1%)
Vomiting	9/31 (29%)		14/32 (43.8%)
Abdominal Pain	5/31 (16.1%)		11/32 (34.4%)
Mucositis Oral	3/31 (9.7%)		8/32 (25%)
Gastrointestinal Disorders - Other	0/31 (0%)		1/32 (3.1%)
Oral Pain	0/31 (0%)		2/32 (6.3%)
Nausea	22/31 (71%)		25/32 (78.1%)
Gastroesophageal Reflux Disease	2/31 (6.5%)		1/32 (3.1%)
Hemorrhoidal Hemorrhage	1/31 (3.2%)		0/32 (0%)
Hemorrhoids	1/31 (3.2%)		0/32 (0%)
Toothache	0/31 (0%)		1/32 (3.1%)
Esophageal Pain	0/31 (0%)		2/32 (6.3%)
Flatulence	0/31 (0%)		1/32 (3.1%)
General disorders
General Disorders And Administration Site Conditions	0/31 (0%)		4/32 (12.5%)
Pain	8/31 (25.8%)		4/32 (12.5%)
Neck Edema	0/31 (0%)		1/32 (3.1%)
Malaise	1/31 (3.2%)		1/32 (3.1%)
Injection Site Reaction	1/31 (3.2%)		0/32 (0%)
Flu Like Symptoms	1/31 (3.2%)		1/32 (3.1%)
Non-Cardiac Chest Pain	1/31 (3.2%)		2/32 (6.3%)
Edema Limbs	3/31 (9.7%)		7/32 (21.9%)
Fatigue	23/31 (74.2%)		23/32 (71.9%)
Fever	4/31 (12.9%)		4/32 (12.5%)
Chills	1/31 (3.2%)		2/32 (6.3%)
Infusion Related Reaction	2/31 (6.5%)		3/32 (9.4%)
Immune system disorders
Allergic Reaction	1/31 (3.2%)		1/32 (3.1%)
Infections and infestations
Wound Infection	0/31 (0%)		1/32 (3.1%)
Upper Respiratory Infection	1/31 (3.2%)		0/32 (0%)
Skin Infection	2/31 (6.5%)		0/32 (0%)
Sinusitis	3/31 (9.7%)		1/32 (3.1%)
Papulopustular Rash	1/31 (3.2%)		0/32 (0%)
Mucosal Infection	0/31 (0%)		2/32 (6.3%)
Lung Infection	1/31 (3.2%)		0/32 (0%)
Eye Infection	1/31 (3.2%)		0/32 (0%)
Vaginal Infection	2/31 (6.5%)		1/32 (3.1%)
Urinary Tract Infection	0/31 (0%)		3/32 (9.4%)
Catheter Related Infection	0/31 (0%)		1/32 (3.1%)
Bronchial Infection	0/31 (0%)		1/32 (3.1%)
Enterocolitis Infectious	0/31 (0%)		1/32 (3.1%)
Injury, poisoning and procedural complications
Vascular Access Complication	0/31 (0%)		1/32 (3.1%)
Fall	1/31 (3.2%)		1/32 (3.1%)
Wound Complication	1/31 (3.2%)		0/32 (0%)
Burn	0/31 (0%)		1/32 (3.1%)
Bruising	1/31 (3.2%)		1/32 (3.1%)
Investigations
Investigations - Other	1/31 (3.2%)		2/32 (6.3%)
Weight Loss	1/31 (3.2%)		2/32 (6.3%)
Weight Gain	1/31 (3.2%)		4/32 (12.5%)
Platelet Count Decreased	17/31 (54.8%)		15/32 (46.9%)
Lymphocyte Count Decreased	0/31 (0%)		6/32 (18.8%)
Ggt Increased	1/31 (3.2%)		0/32 (0%)
Creatinine Increased	1/31 (3.2%)		1/32 (3.1%)
Cholesterol High	0/31 (0%)		1/32 (3.1%)
Neutrophil Count Decreased	26/31 (83.9%)		29/32 (90.6%)
Carbon Monoxide Diffusing Capacity Decreased	0/31 (0%)		1/32 (3.1%)
White Blood Cell Decreased	22/31 (71%)		27/32 (84.4%)
Aspartate Aminotransferase Increased	4/31 (12.9%)		1/32 (3.1%)
Alkaline Phosphatase Increased	3/31 (9.7%)		4/32 (12.5%)
Alanine Aminotransferase Increased	2/31 (6.5%)		3/32 (9.4%)
Metabolism and nutrition disorders
Hypophosphatemia	0/31 (0%)		2/32 (6.3%)
Hyponatremia	3/31 (9.7%)		5/32 (15.6%)
Hypomagnesemia	7/31 (22.6%)		6/32 (18.8%)
Hypokalemia	1/31 (3.2%)		8/32 (25%)
Hypoglycemia	0/31 (0%)		2/32 (6.3%)
Hypocalcemia	3/31 (9.7%)		5/32 (15.6%)
Hypoalbuminemia	2/31 (6.5%)		3/32 (9.4%)
Hypertriglyceridemia	0/31 (0%)		1/32 (3.1%)
Hypernatremia	1/31 (3.2%)		1/32 (3.1%)
Hypermagnesemia	1/31 (3.2%)		1/32 (3.1%)
Hyperkalemia	1/31 (3.2%)		2/32 (6.3%)
Hyperglycemia	5/31 (16.1%)		4/32 (12.5%)
Hypercalcemia	0/31 (0%)		2/32 (6.3%)
Dehydration	2/31 (6.5%)		1/32 (3.1%)
Anorexia	10/31 (32.3%)		6/32 (18.8%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	4/31 (12.9%)		1/32 (3.1%)
Myalgia	8/31 (25.8%)		3/32 (9.4%)
Muscle Weakness Lower Limb	1/31 (3.2%)		0/32 (0%)
Generalized Muscle Weakness	3/31 (9.7%)		3/32 (9.4%)
Flank Pain	0/31 (0%)		2/32 (6.3%)
Bone Pain	6/31 (19.4%)		1/32 (3.1%)
Back Pain	4/31 (12.9%)		5/32 (15.6%)
Arthritis	1/31 (3.2%)		0/32 (0%)
Arthralgia	7/31 (22.6%)		5/32 (15.6%)
Musculoskeletal And Connective Tissue Disorder - Other	0/31 (0%)		2/32 (6.3%)
Nervous system disorders
Tremor	1/31 (3.2%)		1/32 (3.1%)
Presyncope	0/31 (0%)		1/32 (3.1%)
Peripheral Sensory Neuropathy	19/31 (61.3%)		13/32 (40.6%)
Peripheral Motor Neuropathy	1/31 (3.2%)		1/32 (3.1%)
Paresthesia	1/31 (3.2%)		0/32 (0%)
Memory Impairment	3/31 (9.7%)		0/32 (0%)
Headache	7/31 (22.6%)		12/32 (37.5%)
Extrapyramidal Disorder	0/31 (0%)		1/32 (3.1%)
Dysgeusia	2/31 (6.5%)		2/32 (6.3%)
Syncope	1/31 (3.2%)		1/32 (3.1%)
Dizziness	3/31 (9.7%)		6/32 (18.8%)
Cognitive Disturbance	0/31 (0%)		1/32 (3.1%)
Psychiatric disorders
Restlessness	1/31 (3.2%)		0/32 (0%)
Insomnia	8/31 (25.8%)		6/32 (18.8%)
Depression	4/31 (12.9%)		7/32 (21.9%)
Confusion	1/31 (3.2%)		1/32 (3.1%)
Anxiety	5/31 (16.1%)		6/32 (18.8%)
Renal and urinary disorders
Urinary Urgency	0/31 (0%)		1/32 (3.1%)
Urinary Incontinence	1/31 (3.2%)		1/32 (3.1%)
Urinary Tract Pain	1/31 (3.2%)		4/32 (12.5%)
Urinary Frequency	2/31 (6.5%)		1/32 (3.1%)
Proteinuria	0/31 (0%)		1/32 (3.1%)
Cystitis Noninfective	0/31 (0%)		1/32 (3.1%)
Acute Kidney Injury	0/31 (0%)		2/32 (6.3%)
Reproductive system and breast disorders
Vaginal Hemorrhage	1/31 (3.2%)		3/32 (9.4%)
Vaginal Dryness	0/31 (0%)		1/32 (3.1%)
Pelvic Pain	2/31 (6.5%)		0/32 (0%)
Vaginal Discharge	3/31 (9.7%)		1/32 (3.1%)
Dyspareunia	0/31 (0%)		1/32 (3.1%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic And Mediastinal Disorders - Other	1/31 (3.2%)		1/32 (3.1%)
Sore Throat	1/31 (3.2%)		1/32 (3.1%)
Sneezing	0/31 (0%)		1/32 (3.1%)
Postnasal Drip	1/31 (3.2%)		1/32 (3.1%)
Pleural Effusion	0/31 (0%)		1/32 (3.1%)
Nasal Congestion	5/31 (16.1%)		2/32 (6.3%)
Pleuritic Pain	0/31 (0%)		1/32 (3.1%)
Laryngeal Inflammation	1/31 (3.2%)		0/32 (0%)
Hoarseness	0/31 (0%)		1/32 (3.1%)
Hiccups	1/31 (3.2%)		0/32 (0%)
Epistaxis	1/31 (3.2%)		0/32 (0%)
Dyspnea	7/31 (22.6%)		9/32 (28.1%)
Cough	8/31 (25.8%)		5/32 (15.6%)
Allergic Rhinitis	0/31 (0%)		2/32 (6.3%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	2/31 (6.5%)		0/32 (0%)
Skin Hyperpigmentation	0/31 (0%)		3/32 (9.4%)
Scalp Pain	1/31 (3.2%)		1/32 (3.1%)
Rash Acneiform	1/31 (3.2%)		2/32 (6.3%)
Pruritus	1/31 (3.2%)		2/32 (6.3%)
Rash Maculo-Papular	1/31 (3.2%)		3/32 (9.4%)
Nail Discoloration	0/31 (0%)		2/32 (6.3%)
Dry Skin	1/31 (3.2%)		2/32 (6.3%)
Alopecia	25/31 (80.6%)		19/32 (59.4%)
Vascular disorders
Thromboembolic Event	0/31 (0%)		2/32 (6.3%)
Phlebitis	1/31 (3.2%)		0/32 (0%)
Hypotension	3/31 (9.7%)		0/32 (0%)
Hypertension	6/31 (19.4%)		5/32 (15.6%)
Hot Flashes	8/31 (25.8%)		6/32 (18.8%)
Hematoma	1/31 (3.2%)		0/32 (0%)
Flushing	3/31 (9.7%)		0/32 (0%)

Limitations/Caveats

An interim analysis was planned occur after 20 PFS events were observed in either arm (roughly 50% information time). The futility threshold for paclitaxel and carboplatin relative to BEP was HR>1.10. Median followup time was 48 months. The study closed at the interim analysis for futility, and difficulty with accrual. At the time of closures, 63 of a planned 128 patients had enrolled at the time of accrual suspension.

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.