Temsirolimus, Carboplatin, and Paclitaxel as First-Line Therapy in Treating Patients With Newly Diagnosed Stage III-IV Clear Cell Ovarian Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01196429
• Collaborator: NRG Oncology (Other)
• Enrollment: 90
• Locations: 145
• Arm: 1
• Duration (Months): 53
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well temsirolimus, carboplatin, and paclitaxel as first-line therapy works in treating patients with newly diagnosed stage III-IV clear cell ovarian cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with combination chemotherapy may be an effective treatment for ovarian cancer.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Clear Cell Cystadenocarcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer	Drug: Carboplatin; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Temsirolimus	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the activity of the study regimen as measured by the proportion of patients who are alive and progression-free for at least 12 months after study entry in patients with newly diagnosed stage III or IV clear cell ovarian cancer in the following populations: patients in the United States (U.S.) and worldwide (outside of Japan) and patients in Japan.

2. To compare progression-free survival in newly diagnosed stage III or IV clear cell ovarian cancer patients in patients in the U.S. and worldwide (outside of Japan) versus patients in Japan.

SECONDARY OBJECTIVES:

1. To characterize the duration of overall survival and progression-free survival in each population.

2. To examine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4 in each population.

3. To estimate the rate of objective tumor response in patients with measurable disease.

TERTIARY OBJECTIVES:

1. To explore whether immunohistochemical (IHC) expression of components of the mammalian target of rapamycin (mTOR) signaling pathway (phosphatase and tensin homolog [PTEN], total and phosphorylated protein kinase B [Akt], as well as, ATP-binding cassette, sub-family C [CFTR/MRP], member 3 [ABCC3] [MRP3], ATPase, H+ transporting, lysosomal accessory protein 1 [AB CF2], cyclin E, and vascular endothelial growth factor [VEGF]) are associated with outcome, nationality or clinical characteristics.

2. To explore whether there is any differences in differential gene expression profiles between U.S. and worldwide (outside of Japan) versus Japanese patients.

OUTLINE:

Patients receive paclitaxel* intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity.

NOTE: * For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Temsirolimus (CCI-779) (NCI Supplied Agent: NSC# 683864,) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus Consolidation as First-Line Therapy in the Treatment of Clear Cell Carcinoma of the Ovary
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (paclitaxel, carboplatin, temsirolimus, docetaxel) Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity. NOTE: * For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour.

Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Drug: Docetaxel; Given IV; Other Names: RP56976 Taxotere Taxotere Injection Concentrate ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Drug: Temsirolimus; Given IV; Other Names: CCI-779 CCI-779 Rapamycin Analog Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Who Are Alive and Progression-free for at Least 12 Months After Study Entry in Patients With Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer in the Following Populations: Patients in the U.S./Worldwide and Japan [Tumor scans were done every other cycle for the first 6 months; then every 3 months x2; then every 6 months thereafter; and at any other time if clinically indicated or signs suggestive of progressive disease or rising levels; for up to 5 years.]

   Progression of target lesions (TL) was a >=20% increase in the sum of the diameters of TL, taking as reference the smallest sum on study (including the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must demonstrate an absolute increase >=5 mm. Progression of non-target lesions (NTL) as defined as appearance of >=1 new lesions or unequivocal progression of existing NTL. Unequivocal progression should not normally trump target lesion status; it must be representative of overall disease status change, not a single lesion increase. Clear progression of only NTL is exceptional, but the opinion of the treating physician should prevail in such circumstances, and the progression status should be later confirmed by a review panel (or Principal Investigator). Progression of TL, unequivocal progression of NTL, or new lesions constitutes progression. This description is abbreviated; see the RECIST 1.1 manuscript for further details.

2. Compare Progression-free Survival in Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer Patients in Patients in the U.S. and Worldwide (Outside of Japan) Versus Patients in Japan. [Tumor scans were done every other cycle for the first 6 months;then every 3 mnths x2;then every 6 mnths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggesting progressive dx or rising serum tumor marker le]

   Progression-free survival (PFS) was defined s the period from study entry until disease progression, death, or the last date of contact. Progression was based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Outcome measure data not reported because protocol stated "If the combination is declared active (i.e. HO is rejected) in one or both of the populations, the two populations will be compared with respect to PFS using a logrank test stratified by optimal/suboptimal disease status." The combination was not declared active in either population.

3. Frequency and Severity of Toxicity [Each cycle while on treatment]

   Grade 3 or higher adverse events were graded by CTC AE v4

Secondary Outcome Measures

1. Progression-free Survival [Tumor scans were done every other cycle for the first 6 months; then every 3 months x 2; then every 6 mths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising tumor mark]

   Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1

2. Overall Survival [Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.]

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

3. Objective Tumor Response [Every other cycle for first 6 months; then every 3 months for two years; then every six months for the next three years; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tu]

   Complete and Partial Tumor Response by RECIST 1.1. RECIST1.1 is a multi-page paper, and response is defined in the protocol across multiple pages, so it is not practical to define response here.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have stage III or IV clear cell ovarian cancer; primary tumors must be at least 50% clear cell histomorphology in order to be eligible; in addition, the tumors should be negative for expression of Wilms tumor 1 (WT-1) antigen and estrogen receptor (ER) antigen by immunohistochemistry; appropriate tissue sections to confirm stage and histologic classification of cell type must be sent to Gynecologic Oncology Group (GOG) for central pathology review; immunohistochemical stained slides for ER and WT-1 antigen must be also be submitted to GOG for pathology review

• Patients who have met the pre-entry requirements

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

• Patients with a GOG performance status of 0, 1, or 2

• Patients must be entered between 2 and 12 weeks after initial surgery; performed for the combined purpose of diagnosis, staging and cytoreduction

• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])

• Absolute neutrophil count >= 1,500/mcl

• Platelets >= 100,000/mcl

• Total bilirubin within normal institutional limits

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times institutional upper limit of normal (< 5 times upper limit of normal [ULN] for subjects with liver metastases)

• Alkaline phosphatase =< 2.5 times institutional upper limit of normal (< 5 times ULN for subjects with liver metastases)

• Creatinine =< 1.5 x institutional upper limit of normal, grade 1 per CTCAE v. 4.0

• Cholesterol =< 350 mg/dL (fasting)

• Triglycerides =< 400 mg/dL (fasting)

• Albumin >= 3.0 g/dL

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus)

• Partial thromboplastin time (PTT) < 1.2 times the upper limit of normal

• Neurologic function (sensory and motor) =< CTCAE grade 1

Exclusion Criteria:

• 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 who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than five years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their clear cell ovarian cancer

• Patients with primary peritoneal and fallopian tube carcinoma are not eligible

• Previous treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus), paclitaxel, or carboplatin

• Patients cannot be receiving enzyme-inducing antiepileptic drugs (enzyme-inducing antiepileptic drugs [EIAEDs]; e.g., phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's Wort; use of agents that potently inhibit CYP3A4 (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited; the appropriateness of use of such agents is left to physician discretion; strong CYP3A4 inhibitors are prohibited

• Patients receiving any investigational agents

• Patients with severely impaired lung function defined as a diffusion lung capacity for carbon monoxide (DLCO) =< 50% of the normal predicted value and/or oxygen (O2) saturation =< 88% at rest on room air

• Patients with symptomatic congestive heart failure of New York Heart Association class III or IV, unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant disease

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• Patients on maintenance corticosteroids are ineligible with the exception of short term use (fewer than 5 days)

• Patients with baseline requirement for oxygen

• Patients with serious concomitant illness which, in the opinion of the treating physician, will place patient at unreasonable risk from therapy on this protocol

• Patients who are pregnant or nursing; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of study therapies

• Patients with poorly controlled diabetes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
2	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
3	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
4	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
5	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
6	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
7	Hartford Hospital	Hartford	Connecticut	United States	06102
8	Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
9	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
10	Florida Hospital Orlando	Orlando	Florida	United States	32803
11	Memorial University Medical Center	Savannah	Georgia	United States	31404
12	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
13	Northwestern University	Chicago	Illinois	United States	60611
14	Rush University Medical Center	Chicago	Illinois	United States	60612
15	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
16	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
17	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
18	Cadence Cancer Center in Warrenville	Warrenville	Illinois	United States	60555
19	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
20	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
21	Elkhart General Hospital	Elkhart	Indiana	United States	46515
22	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
23	Saint Vincent Oncology Center	Indianapolis	Indiana	United States	46260
24	Community Howard Regional Health	Kokomo	Indiana	United States	46904
25	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
26	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
27	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
28	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
29	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
30	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
31	South Bend Clinic	South Bend	Indiana	United States	46617
32	Northern Indiana Cancer Research Consortium CCOP	South Bend	Indiana	United States	46628
33	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
34	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
35	Iowa Oncology Research Association CCOP	Des Moines	Iowa	United States	50309
36	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
37	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
38	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
39	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
40	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
41	Walter Reed Army Medical Center-Olney	Olney	Maryland	United States	20832
42	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
43	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
44	Baystate Medical Center	Springfield	Massachusetts	United States	01199
45	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
46	Michigan Cancer Research Consortium CCOP	Ann Arbor	Michigan	United States	48106
47	Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48124
48	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
49	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
50	Hurley Medical Center	Flint	Michigan	United States	48502
51	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
52	Gynecologic Oncology of West Michigan PLLC	Grand Rapids	Michigan	United States	49546
53	Allegiance Health	Jackson	Michigan	United States	49201
54	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
55	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
56	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
57	Sparrow Hospital	Lansing	Michigan	United States	48912
58	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
59	Michiana Hematology Oncology PC-Niles	Niles	Michigan	United States	49120
60	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
61	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
62	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
63	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
64	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
65	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
66	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
67	Mercy Hospital-Joplin	Joplin	Missouri	United States	64804
68	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
69	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
70	CoxHealth South Hospital	Springfield	Missouri	United States	65807
71	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
72	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
73	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
74	Winthrop University Hospital	Mineola	New York	United States	11501
75	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
76	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
77	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
78	Duke University Medical Center	Durham	North Carolina	United States	27710
79	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
80	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
81	University of Cincinnati	Cincinnati	Ohio	United States	45267
82	Case Western Reserve University	Cleveland	Ohio	United States	44106
83	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
84	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
85	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
86	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
87	Kettering Medical Center	Kettering	Ohio	United States	45429
88	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
89	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
90	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
91	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
92	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
93	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
94	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
95	Geisinger Medical Group	State College	Pennsylvania	United States	16801
96	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
97	Women and Infants Hospital	Providence	Rhode Island	United States	02905
98	M D Anderson Cancer Center CCOP Research Base	Houston	Texas	United States	77030
99	M D Anderson Cancer Center	Houston	Texas	United States	77030
100	PeaceHealth Medical Group PC	Bellingham	Washington	United States	98226
101	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
102	Harrison Medical Center	Bremerton	Washington	United States	98310
103	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
104	Skagit Valley Hospital Regional Cancer Care Center	Mount Vernon	Washington	United States	98273
105	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
106	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
107	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
108	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
109	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
110	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
111	Northwest Hospital	Seattle	Washington	United States	98133
112	University of Washington Medical Center	Seattle	Washington	United States	98195
113	Olympic Medical Cancer Care Center	Sequim	Washington	United States	98384
114	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
115	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington	United States	99204
116	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
117	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
118	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
119	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
120	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
121	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
122	Tohoku University School of Medicine	Sendai	Aoba-ku	Japan	980-8574
123	Kure National Hospital	Kure	Hiroshima	Japan	737
124	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
125	Hyogo Cancer Center	Akashi-city	Hyogo	Japan	673-8558
126	Iwate Medical University School of Medicine	Morioka	Iwate	Japan	020-8505
127	Kagoshima City Hospital	Kagoshima City	Kagoshima	Japan	890-8760
128	Niigata University Medical and Dental Hospital	Niigata City	Niigata	Japan	951-8520
129	University of the Ryukyus Hospital-Col Health Scnc	Nakagami-gun	Okinawa	Japan	903-0215
130	Shizuoka Cancer Center	Shizuoka City	Suntou	Japan	411-8777
131	Keio University	Shinjuku-ku	Tokyo	Japan	160-8582
132	Shikoku Cancer Center	Matsuyama		Japan	791-0280
133	National Kyushu Cancer Center	Minami-ku		Japan	811 1395
134	Jikei University School of Medicine	Minato-ku, Tokyo		Japan	105-8461
135	Kinki University	Osaka, Osaka		Japan	589 8511
136	Saitama Medical University International Medical Center	Saitama		Japan	350-1298
137	National Cancer Center Hospital	Tokyo		Japan	104 0045
138	Tottori University	Tottori		Japan	680-8550
139	Keimyung University-Dongsan Medical Center	Jung-Ku	Daegu	Korea, Republic of	700-712
140	National Cancer Center-Korea	Goyang-si	Gyeonggi-do	Korea, Republic of	410-769
141	Samsung Medical Center	Seoul	Korea	Korea, Republic of	135-710
142	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
143	Gangnam Severance Hospital	Seoul		Korea, Republic of	135-720
144	Asan Medical Center	Seoul		Korea, Republic of	138-736
145	Korea Cancer Center Hospital	Seoul		Korea, Republic of	139-706

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: John Farley, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01196429
• Other Study ID Numbers: NCI-2011-02653; NCI-2011-02653; CDR0000684262; GOG-0268; GOG-0268; GOG-0268; U10CA180868; U10CA027469
• First Posted: Sep 8, 2010
• Last Update Posted: Aug 8, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma; Sirolimus; Paclitaxel; Docetaxel; Carboplatin; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	The study was activated on 8/30/2010 and closed to accrual on 1/6/2014.
Pre-assignment Detail	Additional details about the interventions administered were not included because these are groups (not arms).

Arm/Group Title	US/Korea	Japan
Arm/Group Description	Temsirolimus (CCI-779) 25mg IV Days 1 and 8, Carboplatin AUC= 6 IV Day 1 and Paclitaxel 175 mg/m2 IV on Day 1 every 3 weeks for cycles 1-6 or disease progression. Followed by consolidation therapy with temsirolimus (CCI-779) 25 mg weekly on Days 1, 8 and 15 every 3 weeks cycles 7-17 or until disease progression	Temsirolimus (CCI-779) 25mg IV Days 1 and 8, Carboplatin AUC= 6 IV Day 1 and Paclitaxel 175 mg/m2 IV on Day 1 every 3 weeks for cycles 1-6 or disease progression. Followed by consolidation therapy with temsirolimus (CCI-779) 25 mg weekly on Days 1, 8 and 15 every 3 weeks cycles 7-17 or until disease progression
Period Title: Overall Study
STARTED	45	45
COMPLETED	42	45
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	US/Korea	Japan	Total
Arm/Group Description	Temsirolimus (CCI-779) 25mg IV Days 1 and 8, Carboplatin AUC= 6 IV Day 1 and Paclitaxel 175 mg/m2 IV on Day 1 every 3 weeks for cycles 1-6 or disease progression. Followed by consolidation therapy with temsirolimus (CCI-779) 25 mg weekly on Days 1, 8 and 15 every 3 weeks cycles 7-17 or until disease progression	Temsirolimus (CCI-779) 25mg IV Days 1 and 8, Carboplatin AUC= 6 IV Day 1 and Paclitaxel 175 mg/m2 IV on Day 1 every 3 weeks for cycles 1-6 or disease progression. Followed by consolidation therapy with temsirolimus (CCI-779) 25 mg weekly on Days 1, 8 and 15 every 3 weeks cycles 7-17 or until disease progression	Total of all reporting groups
Overall Participants	42	45	87
Age, Customized (participants) [Number]
20-29 years	1 2.4%	1 2.2%	2 2.3%
30-39 years	2 4.8%	3 6.7%	5 5.7%
40-49 years	12 28.6%	9 20%	21 24.1%
50-59 years	21 50%	21 46.7%	42 48.3%
60-69 years	6 14.3%	8 17.8%	14 16.1%
70-79 years	0 0%	3 6.7%	3 3.4%
80-89 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	42 100%	45 100%	87 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Are Alive and Progression-free for at Least 12 Months After Study Entry in Patients With Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer in the Following Populations: Patients in the U.S./Worldwide and Japan
Description	Progression of target lesions (TL) was a >=20% increase in the sum of the diameters of TL, taking as reference the smallest sum on study (including the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must demonstrate an absolute increase >=5 mm. Progression of non-target lesions (NTL) as defined as appearance of >=1 new lesions or unequivocal progression of existing NTL. Unequivocal progression should not normally trump target lesion status; it must be representative of overall disease status change, not a single lesion increase. Clear progression of only NTL is exceptional, but the opinion of the treating physician should prevail in such circumstances, and the progression status should be later confirmed by a review panel (or Principal Investigator). Progression of TL, unequivocal progression of NTL, or new lesions constitutes progression. This description is abbreviated; see the RECIST 1.1 manuscript for further details.
Time Frame	Tumor scans were done every other cycle for the first 6 months; then every 3 months x2; then every 6 months thereafter; and at any other time if clinically indicated or signs suggestive of progressive disease or rising levels; for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	US/Korea	Japan
Arm/Group Description	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Patients censored prior to 12 months were considered failures in this analysis. Progression was based on RECIST 1.1	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Patients censored prior to 12 months were considered failures in this analysis. Progression was based on RECIST 1.1
Measure Participants	42	45
Number (90% Confidence Interval) [percentage of participants]	43 102.4%	53 117.8%

2. Primary Outcome

Title	Compare Progression-free Survival in Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer Patients in Patients in the U.S. and Worldwide (Outside of Japan) Versus Patients in Japan.
Description	Progression-free survival (PFS) was defined s the period from study entry until disease progression, death, or the last date of contact. Progression was based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Outcome measure data not reported because protocol stated "If the combination is declared active (i.e. HO is rejected) in one or both of the populations, the two populations will be compared with respect to PFS using a logrank test stratified by optimal/suboptimal disease status." The combination was not declared active in either population.
Time Frame	Tumor scans were done every other cycle for the first 6 months;then every 3 mnths x2;then every 6 mnths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggesting progressive dx or rising serum tumor marker le

Outcome Measure Data

Analysis Population Description

The protocol stated "if the combination is declared active (i.e., HO is rejected) in one or both of the populations, the two populations will be compared with respect to PFS using a logrank test stratified by optimal/suboptimal disease status". The combination was not declared active in either population.

Arm/Group Title	US/Korea	Japan
Arm/Group Description	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Patients censored prior to 12 months were considered failures in this analysis. Progression was based on RECIST 1.1	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Patients censored prior to 12 months were considered failures in this analysis. Progression was based on RECIST 1.1
Measure Participants	0	0

3. Primary Outcome

Title	Frequency and Severity of Toxicity
Description	Grade 3 or higher adverse events were graded by CTC AE v4
Time Frame	Each cycle while on treatment

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	US/Korea	Japan
Arm/Group Description	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Patients censored prior to 12 months were considered failures in this analysis. Progression was based on RECIST 1.1	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Patients censored prior to 12 months were considered failures in this analysis. Progression was based on RECIST 1.1
Measure Participants	42	45
Neutrophil count decreased	36 85.7%	42 93.3%
White blood cell decreased	27 64.3%	32 71.1%
Anemia	9 21.4%	13 28.9%
Platelet count decreased	10 23.8%	10 22.2%
Hypertension	4 9.5%	10 22.2%
hypertriglyceridemia	6 14.3%	7 15.6%
Mucositis oral	5 11.9%	5 11.1%
Febrile neutropenia	4 9.5%	5 11.1%
Diarrhea	6 14.3%	2 4.4%
Hypokalemia	3 7.1%	4 8.9%
Hyperglycemia	4 9.5%	2 4.4%
Abdominal pain	3 7.1%	1 2.2%
Lymphocyte count decreased	2 4.8%	2 4.4%
Nausea	1 2.4%	2 4.4%
Urinary tract infection	3 7.1%	0 0%
GGT increased	0 0%	3 6.7%
Edema limbs	2 4.8%	0 0%
Fatigue	1 2.4%	1 2.2%
Fever	1 2.4%	1 2.2%
Non-cardiac chest pain	2 4.8%	0 0%
Cholesterol high	0 0%	2 4.4%
Weight gain	2 4.8%	0 0%
Hypoalbuminemia	1 2.4%	1 2.2%
Hyponatremia	2 4.8%	0 0%
Hypophosphatemia	0 0%	2 4.4%
Peripheral Sensory neuropathy	0 0%	2 4.4%
Cough	2 4.8%	0 0%
Dyspnea	2 4.8%	0 0%
Pharyngeal mucositis	0 0%	2 4.4%
Rash maculo-papular	1 2.4%	1 2.2%
Colonic perforation	0 0%	1 2.2%
Constipation	1 2.4%	0 0%
Ileus	1 2.4%	0 0%
Oral pain	1 2.4%	0 0%
Small intestinal obstruction	1 2.4%	0 0%
Vomiting	1 2.4%	0 0%
Pain	1 2.4%	0 0%
Cholecystitis	1 2.4%	0 0%
Hepatobiliary disorders-other	0 0%	1 2.2%
Appendicitis perforated	0 0%	1 2.2%
Kidney infection	1 2.4%	0 0%
Lung infection	1 2.4%	0 0%
Peripherl nerve infection	1 2.4%	0 0%
Pharyngitis	0 0%	1 2.2%
Skin infection	1 2.4%	0 0%
Infections and infestations -other	1 2.4%	0 0%
Alanine aminotransferase increased	0 0%	1 2.2%
Aspartate aminotransferase increased	0 0%	1 2.2%
Creatiine increased	0 0%	1 2.2%
Anorexia	0 0%	1 2.2%
Dehydration	1 2.4%	0 0%
Hypermagnesemia	0 0%	1 2.2%
Back Pain	1 2.4%	0 0%
Bone Pain	1 2.4%	0 0%
Flank pain	1 2.4%	0 0%
Pain in Extremity	1 2.4%	0 0%
Dizziness	0 0%	1 2.2%
Paresthesia	1 2.4%	0 0%
Vasovagal reaction	1 2.4%	0 0%
Anxiety	1 2.4%	0 0%
Dysparenuia	1 2.4%	0 0%
Pneumonitis	0 0%	1 2.2%
Sore throat	1 2.4%	0 0%
Hypotension	1 2.4%	0 0%
Lymphocele	1 2.4%	0 0%

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1
Time Frame	Tumor scans were done every other cycle for the first 6 months; then every 3 months x 2; then every 6 mths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising tumor mark

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	US/Korea	Japan
Arm/Group Description	Patients enrolled from the U.S.and Korea	Patients enrolled from Japan
Measure Participants	42	45
Median (90% Confidence Interval) [months]	11.0	12.1

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame	Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	US/Korea	Japan
Arm/Group Description	Patients enrolled from the U.S.and Korea	Patients enrolled from Japan
Measure Participants	42	45
Median (90% Confidence Interval) [months]	22.6	25.6

6. Secondary Outcome

Title	Objective Tumor Response
Description	Complete and Partial Tumor Response by RECIST 1.1. RECIST1.1 is a multi-page paper, and response is defined in the protocol across multiple pages, so it is not practical to define response here.
Time Frame	Every other cycle for first 6 months; then every 3 months for two years; then every six months for the next three years; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tu

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	US/Korea	Japan
Arm/Group Description	Patients enrolled from the U.S.and Korea	Patients enrolled from Japan
Measure Participants	42	45
Number (90% Confidence Interval) [percentage of participants]	54 128.6%	71 157.8%

Adverse Events

Time Frame	Study Treatment
Arm/Group Title	US/Korea		Japan
Arm/Group Description	Temsirolimus (CCI-779) 25mg IV Days 1 and 8, Carboplatin AUC= 6 IV Day 1 and Paclitaxel 175 mg/m2 IV on Day 1 every 3 weeks for cycles 1-6 or disease progression. Followed by consolidation therapy with temsirolimus (CCI-779) 25 mg weekly on Days 1, 8 and 15 every 3 weeks cycles 7-17 or until disease progression		Temsirolimus (CCI-779) 25mg IV Days 1 and 8, Carboplatin AUC= 6 IV Day 1 and Paclitaxel 175 mg/m2 IV on Day 1 every 3 weeks for cycles 1-6 or disease progression. Followed by consolidation therapy with temsirolimus (CCI-779) 25 mg weekly on Days 1, 8 and 15 every 3 weeks cycles 7-17 or until disease progression
All Cause Mortality
	US/Korea		Japan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	US/Korea		Japan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/42 (26.2%)		8/45 (17.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/42 (2.4%)		0/45 (0%)
Gastrointestinal disorders
Small Intestinal Obstruction	1/42 (2.4%)		0/45 (0%)
Abdominal Pain	2/42 (4.8%)		0/45 (0%)
Mucositis Oral	1/42 (2.4%)		0/45 (0%)
General disorders
Non-Cardiac Chest Pain	1/42 (2.4%)		0/45 (0%)
Fever	1/42 (2.4%)		1/45 (2.2%)
Hepatobiliary disorders
Hepatobiliary Disorders - Other	0/42 (0%)		1/45 (2.2%)
Cholecystitis	2/42 (4.8%)		0/45 (0%)
Infections and infestations
Kidney Infection	1/42 (2.4%)		0/45 (0%)
Urinary Tract Infection	1/42 (2.4%)		0/45 (0%)
Appendicitis Perforated	0/42 (0%)		1/45 (2.2%)
Investigations
Platelet Count Decreased	0/42 (0%)		2/45 (4.4%)
Neutrophil Count Decreased	5/42 (11.9%)		1/45 (2.2%)
White Blood Cell Decreased	1/42 (2.4%)		0/45 (0%)
Metabolism and nutrition disorders
Hypertriglyceridemia	2/42 (4.8%)		0/45 (0%)
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness	1/42 (2.4%)		0/45 (0%)
Back Pain	1/42 (2.4%)		0/45 (0%)
Nervous system disorders
Dizziness	0/42 (0%)		1/45 (2.2%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/42 (2.4%)		0/45 (0%)
Pharyngeal Mucositis	0/42 (0%)		1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	US/Korea		Japan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/42 (100%)		45/45 (100%)
Blood and lymphatic system disorders
Lymph Node Pain	1/42 (2.4%)		0/45 (0%)
Anemia	42/42 (100%)		45/45 (100%)
Febrile Neutropenia	3/42 (7.1%)		5/45 (11.1%)
Cardiac disorders
Atrial Fibrillation	1/42 (2.4%)		0/45 (0%)
Palpitations	3/42 (7.1%)		4/45 (8.9%)
Sinus Tachycardia	3/42 (7.1%)		3/45 (6.7%)
Chest Pain - Cardiac	0/42 (0%)		3/45 (6.7%)
Ear and labyrinth disorders
Vertigo	0/42 (0%)		2/45 (4.4%)
Tinnitus	9/42 (21.4%)		0/45 (0%)
Hearing Impaired	2/42 (4.8%)		0/45 (0%)
Ear Pain	1/42 (2.4%)		0/45 (0%)
Endocrine disorders
Hypothyroidism	1/42 (2.4%)		0/45 (0%)
Hypoparathyroidism	1/42 (2.4%)		0/45 (0%)
Eye disorders
Watering Eyes	0/42 (0%)		1/45 (2.2%)
Conjunctivitis	0/42 (0%)		7/45 (15.6%)
Blurred Vision	8/42 (19%)		0/45 (0%)
Dry Eye	2/42 (4.8%)		2/45 (4.4%)
Gastrointestinal disorders
Enterocolitis	0/42 (0%)		1/45 (2.2%)
Dysphagia	7/42 (16.7%)		0/45 (0%)
Dyspepsia	8/42 (19%)		1/45 (2.2%)
Colonic Perforation	0/42 (0%)		1/45 (2.2%)
Colitis	1/42 (2.4%)		0/45 (0%)
Constipation	19/42 (45.2%)		21/45 (46.7%)
Diarrhea	24/42 (57.1%)		26/45 (57.8%)
Cheilitis	0/42 (0%)		3/45 (6.7%)
Vomiting	16/42 (38.1%)		18/45 (40%)
Bloating	4/42 (9.5%)		0/45 (0%)
Stomach Pain	0/42 (0%)		8/45 (17.8%)
Anal Mucositis	2/42 (4.8%)		2/45 (4.4%)
Rectal Mucositis	0/42 (0%)		1/45 (2.2%)
Abdominal Pain	17/42 (40.5%)		8/45 (17.8%)
Rectal Hemorrhage	2/42 (4.8%)		0/45 (0%)
Oral Dysesthesia	1/42 (2.4%)		0/45 (0%)
Mucositis Oral	25/42 (59.5%)		40/45 (88.9%)
Gastrointestinal Disorders - Other	2/42 (4.8%)		0/45 (0%)
Anal Pain	0/42 (0%)		1/45 (2.2%)
Oral Hemorrhage	1/42 (2.4%)		0/45 (0%)
Ileus	1/42 (2.4%)		5/45 (11.1%)
Gastrointestinal Pain	1/42 (2.4%)		1/45 (2.2%)
Gingival Pain	1/42 (2.4%)		0/45 (0%)
Oral Pain	4/42 (9.5%)		0/45 (0%)
Abdominal Distension	4/42 (9.5%)		0/45 (0%)
Nausea	28/42 (66.7%)		26/45 (57.8%)
Gastroesophageal Reflux Disease	2/42 (4.8%)		1/45 (2.2%)
Rectal Pain	1/42 (2.4%)		0/45 (0%)
Hemorrhoidal Hemorrhage	1/42 (2.4%)		0/45 (0%)
Hemorrhoids	2/42 (4.8%)		2/45 (4.4%)
Ascites	1/42 (2.4%)		0/45 (0%)
Toothache	0/42 (0%)		3/45 (6.7%)
Esophageal Pain	0/42 (0%)		1/45 (2.2%)
Dental Caries	1/42 (2.4%)		0/45 (0%)
Flatulence	1/42 (2.4%)		0/45 (0%)
Gastritis	0/42 (0%)		3/45 (6.7%)
General disorders
General Disorders And Administration Site Conditio	1/42 (2.4%)		0/45 (0%)
Pain	10/42 (23.8%)		3/45 (6.7%)
Malaise	2/42 (4.8%)		24/45 (53.3%)
Localized Edema	1/42 (2.4%)		0/45 (0%)
Injection Site Reaction	1/42 (2.4%)		1/45 (2.2%)
Infusion Site Extravasation	0/42 (0%)		6/45 (13.3%)
Flu Like Symptoms	4/42 (9.5%)		14/45 (31.1%)
Edema Trunk	1/42 (2.4%)		1/45 (2.2%)
Non-Cardiac Chest Pain	4/42 (9.5%)		0/45 (0%)
Edema Limbs	12/42 (28.6%)		22/45 (48.9%)
Facial Pain	1/42 (2.4%)		0/45 (0%)
Edema Face	4/42 (9.5%)		7/45 (15.6%)
Fatigue	36/42 (85.7%)		19/45 (42.2%)
Fever	8/42 (19%)		8/45 (17.8%)
Gait Disturbance	1/42 (2.4%)		0/45 (0%)
Chills	7/42 (16.7%)		1/45 (2.2%)
Infusion Related Reaction	1/42 (2.4%)		0/45 (0%)
Hepatobiliary disorders
Cholecystitis	1/42 (2.4%)		0/45 (0%)
Immune system disorders
Allergic Reaction	3/42 (7.1%)		3/45 (6.7%)
Infections and infestations
Infections And Infestations - Other	3/42 (7.1%)		0/45 (0%)
Upper Respiratory Infection	4/42 (9.5%)		5/45 (11.1%)
Vulval Infection	0/42 (0%)		1/45 (2.2%)
Skin Infection	3/42 (7.1%)		4/45 (8.9%)
Sinusitis	3/42 (7.1%)		0/45 (0%)
Rash Pustular	0/42 (0%)		1/45 (2.2%)
Pharyngitis	0/42 (0%)		3/45 (6.7%)
Peripheral Nerve Infection	1/42 (2.4%)		0/45 (0%)
Otitis Media	1/42 (2.4%)		0/45 (0%)
Papulopustular Rash	0/42 (0%)		1/45 (2.2%)
Nail Infection	2/42 (4.8%)		0/45 (0%)
Mucosal Infection	2/42 (4.8%)		0/45 (0%)
Lung Infection	2/42 (4.8%)		1/45 (2.2%)
Paronychia	0/42 (0%)		8/45 (17.8%)
Eye Infection	1/42 (2.4%)		1/45 (2.2%)
Small Intestine Infection	1/42 (2.4%)		0/45 (0%)
Gum Infection	0/42 (0%)		2/45 (4.4%)
Vaginal Infection	2/42 (4.8%)		0/45 (0%)
Urinary Tract Infection	6/42 (14.3%)		2/45 (4.4%)
Bladder Infection	0/42 (0%)		5/45 (11.1%)
Lip Infection	1/42 (2.4%)		1/45 (2.2%)
Injury, poisoning and procedural complications
Wound Dehiscence	0/42 (0%)		1/45 (2.2%)
Fall	1/42 (2.4%)		2/45 (4.4%)
Wound Complication	0/42 (0%)		1/45 (2.2%)
Bruising	2/42 (4.8%)		2/45 (4.4%)
Investigations
Weight Loss	8/42 (19%)		14/45 (31.1%)
Weight Gain	10/42 (23.8%)		10/45 (22.2%)
Serum Amylase Increased	0/42 (0%)		1/45 (2.2%)
Platelet Count Decreased	39/42 (92.9%)		41/45 (91.1%)
Lymphocyte Count Decreased	5/42 (11.9%)		2/45 (4.4%)
Inr Increased	0/42 (0%)		2/45 (4.4%)
Ggt Increased	0/42 (0%)		9/45 (20%)
Creatinine Increased	2/42 (4.8%)		7/45 (15.6%)
Cholesterol High	22/42 (52.4%)		30/45 (66.7%)
Neutrophil Count Decreased	42/42 (100%)		44/45 (97.8%)
Cpk Increased	0/42 (0%)		2/45 (4.4%)
Blood Bilirubin Increased	1/42 (2.4%)		1/45 (2.2%)
White Blood Cell Decreased	42/42 (100%)		45/45 (100%)
Aspartate Aminotransferase Increased	10/42 (23.8%)		16/45 (35.6%)
Alkaline Phosphatase Increased	11/42 (26.2%)		11/45 (24.4%)
Alanine Aminotransferase Increased	12/42 (28.6%)		13/45 (28.9%)
Activated Partial Thromboplastin Time Prolonged	0/42 (0%)		2/45 (4.4%)
Metabolism and nutrition disorders
Hypophosphatemia	5/42 (11.9%)		3/45 (6.7%)
Hyponatremia	9/42 (21.4%)		3/45 (6.7%)
Hypomagnesemia	16/42 (38.1%)		2/45 (4.4%)
Hypokalemia	18/42 (42.9%)		5/45 (11.1%)
Hypoglycemia	3/42 (7.1%)		1/45 (2.2%)
Hypocalcemia	8/42 (19%)		3/45 (6.7%)
Hypoalbuminemia	9/42 (21.4%)		8/45 (17.8%)
Hypertriglyceridemia	23/42 (54.8%)		31/45 (68.9%)
Hypernatremia	3/42 (7.1%)		0/45 (0%)
Hypermagnesemia	0/42 (0%)		3/45 (6.7%)
Hyperkalemia	1/42 (2.4%)		2/45 (4.4%)
Hyperglycemia	19/42 (45.2%)		22/45 (48.9%)
Hypercalcemia	1/42 (2.4%)		0/45 (0%)
Dehydration	7/42 (16.7%)		1/45 (2.2%)
Anorexia	20/42 (47.6%)		30/45 (66.7%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	13/42 (31%)		1/45 (2.2%)
Myositis	0/42 (0%)		1/45 (2.2%)
Myalgia	12/42 (28.6%)		27/45 (60%)
Muscle Weakness Upper Limb	1/42 (2.4%)		0/45 (0%)
Muscle Weakness Lower Limb	2/42 (4.8%)		0/45 (0%)
Joint Range Of Motion Decreased	0/42 (0%)		1/45 (2.2%)
Generalized Muscle Weakness	4/42 (9.5%)		0/45 (0%)
Flank Pain	6/42 (14.3%)		0/45 (0%)
Chest Wall Pain	2/42 (4.8%)		0/45 (0%)
Bone Pain	5/42 (11.9%)		0/45 (0%)
Back Pain	6/42 (14.3%)		7/45 (15.6%)
Arthritis	2/42 (4.8%)		3/45 (6.7%)
Arthralgia	14/42 (33.3%)		25/45 (55.6%)
Musculoskeletal And Connective Tissue Disorder -	1/42 (2.4%)		2/45 (4.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant And Unspecified (Incl	1/42 (2.4%)		0/45 (0%)
Tumor Pain	0/42 (0%)		2/45 (4.4%)
Nervous system disorders
Vasovagal Reaction	1/42 (2.4%)		0/45 (0%)
Tremor	2/42 (4.8%)		0/45 (0%)
Somnolence	0/42 (0%)		3/45 (6.7%)
Presyncope	1/42 (2.4%)		0/45 (0%)
Peripheral Sensory Neuropathy	28/42 (66.7%)		43/45 (95.6%)
Peripheral Motor Neuropathy	3/42 (7.1%)		5/45 (11.1%)
Paresthesia	6/42 (14.3%)		1/45 (2.2%)
Neuralgia	2/42 (4.8%)		2/45 (4.4%)
Memory Impairment	2/42 (4.8%)		0/45 (0%)
Movements Involuntary	1/42 (2.4%)		0/45 (0%)
Hypersomnia	0/42 (0%)		1/45 (2.2%)
Headache	15/42 (35.7%)		10/45 (22.2%)
Dysgeusia	5/42 (11.9%)		24/45 (53.3%)
Sinus Pain	1/42 (2.4%)		0/45 (0%)
Dysesthesia	1/42 (2.4%)		1/45 (2.2%)
Dizziness	7/42 (16.7%)		2/45 (4.4%)
Cognitive Disturbance	1/42 (2.4%)		0/45 (0%)
Ataxia	1/42 (2.4%)		0/45 (0%)
Psychiatric disorders
Personality Change	1/42 (2.4%)		0/45 (0%)
Restlessness	2/42 (4.8%)		0/45 (0%)
Libido Decreased	1/42 (2.4%)		0/45 (0%)
Insomnia	13/42 (31%)		11/45 (24.4%)
Depression	9/42 (21.4%)		2/45 (4.4%)
Confusion	1/42 (2.4%)		0/45 (0%)
Anxiety	14/42 (33.3%)		0/45 (0%)
Anorgasmia	1/42 (2.4%)		0/45 (0%)
Renal and urinary disorders
Urinary Urgency	1/42 (2.4%)		0/45 (0%)
Urinary Incontinence	2/42 (4.8%)		0/45 (0%)
Urinary Tract Pain	7/42 (16.7%)		0/45 (0%)
Urinary Frequency	7/42 (16.7%)		1/45 (2.2%)
Renal Calculi	1/42 (2.4%)		0/45 (0%)
Proteinuria	2/42 (4.8%)		4/45 (8.9%)
Hematuria	1/42 (2.4%)		1/45 (2.2%)
Cystitis Noninfective	0/42 (0%)		3/45 (6.7%)
Chronic Kidney Disease	1/42 (2.4%)		0/45 (0%)
Reproductive system and breast disorders
Vaginal Pain	1/42 (2.4%)		0/45 (0%)
Vaginal Hemorrhage	2/42 (4.8%)		1/45 (2.2%)
Pelvic Pain	1/42 (2.4%)		0/45 (0%)
Vaginal Discharge	1/42 (2.4%)		0/45 (0%)
Vaginal Inflammation	1/42 (2.4%)		0/45 (0%)
Dyspareunia	4/42 (9.5%)		0/45 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic And Mediastinal Disorders -	0/42 (0%)		1/45 (2.2%)
Voice Alteration	1/42 (2.4%)		0/45 (0%)
Sore Throat	2/42 (4.8%)		3/45 (6.7%)
Sneezing	1/42 (2.4%)		0/45 (0%)
Sinus Disorder	2/42 (4.8%)		0/45 (0%)
Postnasal Drip	3/42 (7.1%)		0/45 (0%)
Pneumonitis	1/42 (2.4%)		9/45 (20%)
Pleural Effusion	1/42 (2.4%)		0/45 (0%)
Pharyngolaryngeal Pain	0/42 (0%)		2/45 (4.4%)
Pharyngeal Mucositis	0/42 (0%)		8/45 (17.8%)
Nasal Congestion	6/42 (14.3%)		0/45 (0%)
Pleuritic Pain	1/42 (2.4%)		0/45 (0%)
Laryngeal Mucositis	0/42 (0%)		1/45 (2.2%)
Productive Cough	1/42 (2.4%)		2/45 (4.4%)
Laryngeal Inflammation	0/42 (0%)		1/45 (2.2%)
Hypoxia	0/42 (0%)		1/45 (2.2%)
Hoarseness	2/42 (4.8%)		2/45 (4.4%)
Epistaxis	4/42 (9.5%)		15/45 (33.3%)
Dyspnea	14/42 (33.3%)		7/45 (15.6%)
Cough	9/42 (21.4%)		5/45 (11.1%)
Allergic Rhinitis	2/42 (4.8%)		3/45 (6.7%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	2/42 (4.8%)		5/45 (11.1%)
Urticaria	2/42 (4.8%)		9/45 (20%)
Skin Ulceration	4/42 (9.5%)		0/45 (0%)
Skin Induration	0/42 (0%)		1/45 (2.2%)
Skin Hyperpigmentation	1/42 (2.4%)		1/45 (2.2%)
Skin Atrophy	0/42 (0%)		1/45 (2.2%)
Rash Acneiform	14/42 (33.3%)		18/45 (40%)
Purpura	0/42 (0%)		1/45 (2.2%)
Pruritus	7/42 (16.7%)		12/45 (26.7%)
Periorbital Edema	1/42 (2.4%)		0/45 (0%)
Palmar-Plantar Erythrodysesthesia Syndrome	0/42 (0%)		4/45 (8.9%)
Rash Maculo-Papular	14/42 (33.3%)		18/45 (40%)
Skin Hypopigmentation	0/42 (0%)		1/45 (2.2%)
Nail Ridging	2/42 (4.8%)		4/45 (8.9%)
Nail Loss	0/42 (0%)		4/45 (8.9%)
Nail Discoloration	3/42 (7.1%)		5/45 (11.1%)
Hyperhidrosis	2/42 (4.8%)		0/45 (0%)
Dry Skin	4/42 (9.5%)		6/45 (13.3%)
Bullous Dermatitis	1/42 (2.4%)		0/45 (0%)
Alopecia	30/42 (71.4%)		39/45 (86.7%)
Vascular disorders
Vasculitis	0/42 (0%)		5/45 (11.1%)
Thromboembolic Event	1/42 (2.4%)		0/45 (0%)
Lymphocele	1/42 (2.4%)		0/45 (0%)
Lymphedema	5/42 (11.9%)		7/45 (15.6%)
Hypotension	2/42 (4.8%)		2/45 (4.4%)
Hypertension	15/42 (35.7%)		25/45 (55.6%)
Hot Flashes	9/42 (21.4%)		4/45 (8.9%)
Hematoma	0/42 (0%)		1/45 (2.2%)
Flushing	1/42 (2.4%)		8/45 (17.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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