Phase III Study of ABI-007(Albumin-bound Paclitaxel) Plus Gemcitabine Versus Gemcitabine in Metastatic Adenocarcinoma of the Pancreas

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00844649
• Collaborator: (none)
• Enrollment: 861
• Locations: 193
• Arms: 2
• Actual Duration (Months): 49.3
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase III Metastatic Pancreatic Cancer

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Cancer	Drug: Albumin-bound paclitaxel (ABI-007); Drug: Gemcitabine	Phase 3

Detailed Description

A Phase III, open-label randomized, multicenter trial to compare ABI-007(Albumin-bound Paclitaxel)in combination with gemcitabine administered weekly to standard treatment (gemcitabine monotherapy) with respect to overall survival, objective tumor response rate and Progression Free Survival (PFS) in patients diagnosed with metastatic adenocarcinoma of the pancreas.

Study Design

• Study Type: Interventional
• Actual Enrollment: 861 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase III Study of Weekly ABI-007 Plus Gemcitabine Versus Gemcitabine Alone in Patients With Metastatic Adenocarcinoma of the Pancreas
• Actual Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Sep 17, 2012
• Actual Study Completion Date: Apr 9, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Albumin-bound paclitaxel (ABI-007)/Gemcitabine ABI-007 125 mg/m2 administered in combination with gemcitabine 1000 mg/m2 weekly for 3 weeks followed by one week of rest.	Drug: Albumin-bound paclitaxel (ABI-007); ABI-007 125 mg/m^2 administered by intravenous infusion; Other Names: Abraxane ; Drug: Gemcitabine; Gemcitabine, 1000 mg/m2 administered weekly for 7 weeks, Day 1 through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks, Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward).; Other Names: Gemzar
Active Comparator: Gemcitabine Gemcitabine, 1000 mg/m2 administered weekly for 7 weeks followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks followed by a week of rest (Cycle 2 onward).	Drug: Gemcitabine; Gemcitabine, 1000 mg/m2 administered weekly for 7 weeks, Day 1 through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks, Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward).; Other Names: Gemzar

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [From randomization to death; until the data cut off 17 Sept 2012. The maximum time in follow up was 37 months.]

   Overall survival was defined as the time from the date of randomization to the date of death from all causes. Participants who did not die were censored at the last known time the participant was alive. Patient survival was summarized using Kaplan-Meier methods.

Secondary Outcome Measures

1. Progression-free Survival (PFS) by Independent Radiological Review (IRR) [Randomization until disease progression or death from any cause; Until the data cut off of 17 Sept 2012. The maximum time in follow up was 37 months.]

   Progression-free survival was defined as the time from the date of randomization to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurred earlier. Participants who did not have disease progression or had not died were censored at the date of the last tumor assessment, on or prior to the clinical cutoff, and the patient was progression free. If a patient began a new anti-cancer treatment prior to documented disease progression (or death), the patient was censored at the date of last assessment when the patient was documented as progression free prior to the intervention. Patients with two or more consecutive missing response assessments prior to a visit with documented progression (or death) were censored at the last date of tumor assessment when the patient was documented to be progression free. PFS was summarized using Kaplan-Meier methods.

2. Percentage of Participants Who Achieved an Objective Confirmed Overall Response by Independent Radiological Review (IRR) [Assessment every 4 weeks after initial response; Day 1 to data cut off of 17 Sept 2013; maximum time on study 37 months]

   Objective tumor response was summarized as the percentage of participants who achieved a confirmed complete (CR) or partial response (PR) based on an independent blinded radiology assessment of response using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Using RECIST Version 1.0, participants were to achieve either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the investigator assessment of best overall response during study treatment.

Other Outcome Measures

1. Participants With Treatment Emergent Adverse Events (AE) [Study drug initiation through 30 days after the last dose of study drug or EOS, whichever is later; Up to 696 days]

   A Treatment Emergent Adverse Event (TEAE) is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE.

2. Number of Participants With Dose Reductions [Maximum time on treatment was 666 days]

   The number of participants with dose reductions occurring during the treatment period. Dose reductions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

3. Number of Participants With Dose Interruptions [Maximum time on treatment was 666 days]

   The number of participants with dose interruptions experienced by participants that occurred during the treatment period. Dose interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

4. Number of Participants With Dose Delays/Doses Not Given [Up to 666 days]

   The number of dose delays or doses not given experienced by participants during the treatment period. Dose delays are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities. Treatment delays of no longer than 21 days allowed participants to recover from acute toxicity, otherwise participants were discontinued from further treatment except in the event of peripheral neuropathy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

A participant will be eligible for inclusion in this study only if all of the following criteria are met:

1. Participant has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data. Participants with islet cell neoplasms are excluded.

2. Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to randomization in the study.

3. Patient has one or more metastatic tumors measurable by Computed Tomography (CT) scan or Magnetic resonance imaging (MRI), if patient is allergic to CT contrast media).

4. Male or non-pregnant and non-lactating female, and ≥ 18 years of age. If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test Beta-Human Chorionic Gonadotropin (β-hCG) documented 72 hours prior to the first administration of study drug.

If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug. In addition, male and female patients must utilize contraception after the end of treatment as recommended in the product's Summary of Product Characteristics or Prescribing Information provided in the study manual.

1. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-Fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.

2. Patient has adequate biological parameters as demonstrated by the following blood counts at Baseline (obtained ≤14 days prior to randomization):

Absolute neutrophil count (ANC) ≥ 1.5 × 10^{9/L; Platelet count ≥ 100,000/mm}3 (100 × 10^9/L); Hemoglobin (Hgb) ≥ 9 g/dL.

1. Patient has the following blood chemistry levels at Baseline (obtained ≤14 days prior to randomization):

Aspartate Transaminase (AST), Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Transaminase ( ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤ 5 × ULN is allowed Total bilirubin ≤ ULN Serum creatinine within normal limits or calculated clearance ≥ 60 mL/min/1.73 m^{2 for patients with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For patients with a Body Mass Index (BMI) >30 kg/m}2, lean body weight should be used instead.

1. Patient has acceptable coagulation studies (obtained ≤14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (± 15%).

2. Patient has no clinically significant abnormalities in urinalysis results (obtained ≤14 days prior to randomization).

3. Patient has a Karnofsky performance status (KPS) ≥ 70. Two observers will be required to assess KPS. If discrepant, the one with the lowest assessment will be considered true.

4. Patients should be asymptomatic for jaundice prior to Day 1. Significant or symptomatic amounts of ascites should be drained prior to Day 1. Pain symptoms should be stable and should not require modifications in analgesic management prior to Day 1.

5. Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.

Exclusion Criteria

A patient will not be eligible for inclusion in this study if any of the following criteria apply:

1. Patient has known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).

2. Patient has only locally advanced disease.

3. Patient has experienced a ≥10% decrease in KPS between baseline visit and within 72 hours prior to randomization.

4. Patient has a ≥20% decrease in serum albumin level between baseline visit and within 72 hours prior to randomization.

5. History of malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.

6. Patient uses Coumadin.

7. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.

8. Patient has known historical or active infection with Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C.

9. Patient has undergone major surgery, other than diagnostic surgery (i.e.--surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.

10. Patient has a history of allergy or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the product or comparator Summary of Product Characteristics (SmPC) or Prescribing Information.

11. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).

12. Patients with a history of interstitial lung disease.

13. History of chronic leukemias (e.g., chronic lymphocytic leukemia).

14. Patients with high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year.

15. History of Peripheral Artery Disease (e.g,. claudication, Leo Buerger's disease).

16. Patient has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the patient's safety or the study data integrity.

17. Patient is enrolled in any other clinical protocol or investigational trial.

18. Patient is unwilling or unable to comply with study procedures, or is planning to take vacation for 7 or more consecutive days during the course of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprenhensive Cancer Center at University of Alabama	Birmingham	Alabama	United States	35294
2	Clearview Cancer Institute Oncology Specialities, P.C.	Huntsville	Alabama	United States	35805
3	TGEN Clinical Research Services at Scottsdale Healthcare	Scottsdale	Arizona	United States	85258
4	Mayo Clinic-Scottsdale	Scottsdale	Arizona	United States	85259
5	Northern Arizona Hematology and Oncology Associates-AOA	Sedona	Arizona	United States	86336
6	Arizona Cancer Center, University of Arizona	Tucson	Arizona	United States	85724
7	Genesis Cancer Center	Hot Springs	Arkansas	United States	71913
8	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211
9	City of Hope	Duarte	California	United States	91010
10	Pacific Shores Medical Group	Long Beach	California	United States	90813
11	UCLA	Los Angeles	California	United States	90024
12	Desert Hematology Oncology Medical Group, Inc.	Rancho Mirage	California	United States	92270
13	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
14	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
15	University Cancer Institute, LLC	Boynton Beach	Florida	United States	33426
16	Collaborative Research Group	Boynton Beach	Florida	United States	33435
17	FL Cancer Specialist	Fort Myers	Florida	United States	33916
18	Lakeland Regional Cancer Center	Lakeland	Florida	United States	33805
19	Ocala Oncology Center	Ocala	Florida	United States	34471
20	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
21	Lake County Oncology and Hematology	Tavares	Florida	United States	32778
22	Phoebe Putney Cancer Center	Albany	Georgia	United States	31701
23	Northeast Georgia Cancer Care, LLC	Athens	Georgia	United States	30607
24	Piedmont Hospital Research Institute	Atlanta	Georgia	United States	30309
25	Georgia Cancer Specialists	Atlanta	Georgia	United States	30341
26	Atlanta Cancer Care	Atlanta	Georgia	United States	30342
27	Cancer Care & Hemaotology Specialists of Chicagoland	Arlington Heights	Illinois	United States	60005
28	NorthShore University HealthSystem	Evanston	Illinois	United States	60021
29	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois	United States	60714
30	Illinois Cancer Care	Peoria	Illinois	United States	61615
31	Orchard Research	Skokie	Illinois	United States	60076
32	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
33	Hutchinson Clinic, PA	Hutchinson	Kansas	United States	67502
34	Owsley Brown Frazier Cancer Center	Louisville	Kentucky	United States	40245
35	Hematology Oncology Clinic	Baton Rouge	Louisiana	United States	70809
36	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
37	Central Maine Medical Center	Lewiston	Maine	United States	04240
38	Mercy Hospital Portland, ME	Portland	Maine	United States	04102
39	Maine Center for Cancer Medicine	Scarborough	Maine	United States	04074
40	Sidney Kimmel Comphrensive Cancer Center, John Hopkins University	Baltimore	Maryland	United States	21231
41	Center for Cancer & Blood Disorders	Bethesda	Maryland	United States	20817
42	Lahey Clinic	Burlington	Massachusetts	United States	01805
43	Cancer Center of Excellence/University of MA Medical School	Worcester	Massachusetts	United States	01655
44	St. Mary's/ Duluth Clinic	Duluth	Minnesota	United States	55805
45	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55408
46	University of Minnesota, Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
47	Saint Louis University	Saint Louis	Missouri	United States	63110
48	St. John's Medical Research Institute	Springfield	Missouri	United States	65807
49	The Center for Cancer and Hematologic Disease	Cherry Hill	New Jersey	United States	08003
50	Hem Onc Associates-NM	Albuquerque	New Mexico	United States	87106
51	University of New Mexico	Albuquerque	New Mexico	United States	87131-0001
52	New York Oncology Hematology PC	Albany	New York	United States	12206
53	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
54	Arena Oncology Associates, PC	Lake Success	New York	United States	11042
55	SUNY Upstate Medical University	Syracuse	New York	United States	13210
56	Piedmont Hematology Oncology	Winston-Salem	North Carolina	United States	27103
57	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
58	Mid Ohio Oncology/Hematology Inc	Columbus	Ohio	United States	43219
59	Kettering Medical Center	Kettering	Ohio	United States	45429
60	Signal Point Clinical Research Center, LLC	Middletown	Ohio	United States	45042
61	Cancer Centers of SW OK	Lawton	Oklahoma	United States	73505
62	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma	United States	73104
63	Mercy Physicians of Oklahoma	Oklahoma City	Oklahoma	United States	73112
64	Cancer Care Associates- Tulsa	Tulsa	Oklahoma	United States	74104
65	St. Mary Medical Center Hem-Onc Group, PC	Langhorne	Pennsylvania	United States	19047
66	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania	United States	15232
67	South Carolina Oncology Associates	Columbia	South Carolina	United States	29210
68	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
69	Tennessee Oncology	Nashville	Tennessee	United States	37203
70	Medical City Dallas-US Oncology	Dallas	Texas	United States	75230-2510
71	Texas Oncology, PA	Dallas	Texas	United States	75231-4400
72	Texas Oncology, PA/ Methodist Charlton Cancer Center	Dallas	Texas	United States	75237
73	Texas Oncology Laboratories	Fort Worth	Texas	United States	76104
74	The Center for Cancer and Blood Disorders	Fort Worth	Texas	United States	76104
75	The University of Texas Medical School at Houston	Houston	Texas	United States	77030
76	Texas Oncology- Plano East	Plano	Texas	United States	75075
77	Texas Oncology, PA	Round Rock	Texas	United States	76885
78	Texas Oncology-Round Rock	Round Rock	Texas	United States	78681
79	South Texas Oncology and Hematology, P.A	San Antonio	Texas	United States	78229
80	Texas Oncology, PA	Wichita Falls	Texas	United States	76310
81	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
82	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
83	Fairfax-Northern Virginia Hematology-Oncology, P.C.	Fairfax	Virginia	United States	22031
84	Virginia Cancer Specialist, PC	Fairfax	Virginia	United States	22031
85	Virginia Cancer Institute	Richmond	Virginia	United States	23230
86	Virginia Commonwealth University	Richmond	Virginia	United States	23298-0037
87	Swedish Health Services	Seattle	Washington	United States	98104
88	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
89	Evergreen Hematology & Oncology	Spokane	Washington	United States	99218
90	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
91	Bankstown-Lidcombe Hospital	Bankstown	New South Wales	Australia	2200
92	Macarthur Cancer Therapy Center	Campbelltown	New South Wales	Australia	2560
93	Concord Hospital	Concord	New South Wales	Australia	2139
94	St. Vincent's Hospital	Darlinghurst	New South Wales	Australia	2010
95	Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
96	Newcastle Hospital	Waratah	New South Wales	Australia	2298
97	Southern Medical Day Care Centre	Wollongong	New South Wales	Australia	2500
98	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
99	Haemotology & Oncology Australasia (HOCA)	Milton	Queensland	Australia	4101
100	Haematology Oncology Clinics of Australasia-Gold Coast	Milton	Queensland	Australia	4215
101	Adelaide Cancer Centre (T/A Ashford Cancer Ctr)	Ashford	South Australia	Australia	5035
102	Flinders Medical Center	Bedford Park	South Australia	Australia	5042
103	Calvary North Adelaide Hospital	North Adelaide	South Australia	Australia	5006
104	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
105	Medical Oncology Unit, Bendigo Health	Bendigo	Victoria	Australia	3552
106	Monash Medical Centre	East Bentleigh	Victoria	Australia	3165
107	Western Hospital	Footscray	Victoria	Australia	3011
108	Peninsula Oncology Centre	Frankston	Victoria	Australia	3199
109	Alfred Hospital	Melbourne	Victoria	Australia	3004
110	Border Medical Oncology	Wodonga	Victoria	Australia	3690
111	Sir Charles Gairdner Hospital	Nedlands, Perth	Western Australia	Australia	6009
112	Krankenhaus der Barmherzigen Schwestern Linz	Linz		Austria	4010
113	Landesklinikum St. Pölten	St. Pölten		Austria	3100
114	Medizinische Universität Wien	Vienna		Austria	1090
115	Klinikum Wels-Grieskirchen GmbH	Wels		Austria	4600
116	Imelda VZW , Gastro-Enterology	Bonheiden		Belgium	2820
117	Hôpital Erasme, Gastro-Enterology	Brussels		Belgium	1070
118	AZ Groeninge - Campus Sint-Niklaas	Kortrijk		Belgium	8500
119	H.-Hartziekenhuis Roeselare-Menen vzw	Roeselare		Belgium	8800
120	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
121	BC Cancer Agency-Vancouver	Vancouver	British Columbia	Canada	V5Z 4E6
122	The Royal Victoria Hospital-Barrie	Barrie	Ontario	Canada	L4M6M2
123	Hopital du Sacre-Coeur	Montreal	Quebec	Canada	H4J 1C5
124	Centre Hospitalier de L'Universite de Montreal St-Luc	Montreal		Canada	H2X3J4
125	Princess Margaret Hospital	Ontario		Canada	M5G 2M9
126	Hotel-Dieu de Quebec	Quebec		Canada	G1R 2J6
127	Centre Regional de lutte contre le cancer Paul Papin	Angers		France	49933
128	Hôpital Saint Antoine	Paris		France	75571
129	Hôpital Beaujon	Paris		France	92118
130	Kliniken Essen-Mitte	Essen		Germany	45136
131	Klinikum Freising	Freising		Germany	85354
132	Praxis für Innere Medizin, Dr. Oettle Helmut	Friedrichshafen		Germany	88045
133	LMU Klinikum der Universität	Munich		Germany	81377
134	Klinikum Oldenburg	Oldenburg		Germany	26133
135	Universitätsklinikum Würzburg	Würzburg		Germany	97070
136	I.R.C.C.S. "Giovanni Paolo II" - Istituto Oncologico	Bari		Italy	70124
137	E. O. Ospedali Galliera, Struttura Complessa Oncologia Medica	Genova		Italy	16128
138	Nazionale per la Ricerca sul Cancro	Genova		Italy	16132
139	Fondazione Centro San Raffaele del Monte Tabor	Milano		Italy	20132
140	Oncologia Medica Falck	Milano		Italy	20162
141	Istituto Oncologico Veneto	Padova		Italy	35128
142	IRCCS Policlinico San Matteo	Pavia		Italy	27100
143	Azienda Ospedaliero universitaria Pisana	Pisa		Italy	56126
144	Arcispedale Santa Maria Nuova, Unità Operativa di Oncologia Medica	Reggio Emilia		Italy	42100
145	Arcispedale Santa Maria Nuova	Reggio Emilia		Italy	42100
146	Istituto Nazionale Tumori "Regina Elena"	Roma		Italy	00144
147	Istituto Clinico Humanitas	Rozzano		Italy	20089
148	Ospedale Casa Sollievo della Sofferenza IRCCS	San Giovanni Rotondo, Foggia		Italy	71013
149	Azienda Ospedaliera Universitaria Integrata di Verona	Verona		Italy	37134
150	Med Radiological Centre of the Russian Academy of Med Sciences	Obninsk	Kaluga Region	Russian Federation	249036
151	Tatarstan Republican Onc Ctr	Kazan	Republic Of Tatarstan	Russian Federation	420029
152	Altai Territorial Oncological Center	Barnaul		Russian Federation	656049
153	Chelyabinsk Regional Onc Ctr	Chelyabinsk		Russian Federation	454087
154	Ivanovo Regional Oncology Center	Ivanovo		Russian Federation	153013
155	Regional Oncological Center # 2	Magnitogorsk		Russian Federation	455001
156	Moscow Municipal Onc Hosp #62	Moscow Region		Russian Federation	143423
157	Moscow City Clinical Hosp #57 Chemotherapy Dept	Moscow		Russian Federation	105077
158	Blokhin Cancer Research Center	Moscow		Russian Federation	115478
159	Russian Res Ctr of Radiology under the Fed Agency for Hi-Tech Med Care	Moscow		Russian Federation	117997
160	Russian Research Ctr of Surgery n.a. B.V. Petrovskiy under the Russian Academy of Med Sciences	Moscow		Russian Federation	119992
161	Central Clinical Hosp of the President of the Russian Federation	Moscow		Russian Federation	121356
162	Semashko Central Hosp #2	Moscow		Russian Federation	129128
163	Omsk Regional Onc Ctr	Omsk		Russian Federation	610013
164	Orenburg Regional Onc Ctr	Orenburg		Russian Federation	460021
165	Pyatigorsk Affiliate of Stavropol Regional Onc Ctr	Pyatigorsk		Russian Federation	357500
166	St. Petersburg State Med Academy n.a.Mechnikov	St Petersburg		Russian Federation	195067
167	Russian Research Ctr for Radiology and Surgical Technologies	St Petersburg		Russian Federation	197758
168	Clinical Hosp # 122 n.a. L.G. Sokolov	St. Petersburg		Russian Federation	194291
169	Leningrad Regional Clinical Hosp	St. Petersburg		Russian Federation	194291
170	St. Petersburg City Onc Ctr	St. Petersburg		Russian Federation	198255
171	Tula Regional Oncology Center	Tula		Russian Federation	300053
172	Bashkortostan Republican Onc Ctr	Ufa		Russian Federation	450054
173	Yaroslavl Regional Onc Ctr	Yaroslavl		Russian Federation	150054
174	Hospital Vall D´Hebron	Barcelona		Spain	08035
175	Hospital Clinic i Provincial	Barcelona		Spain	8036
176	Hospital Universitario Reina Sofia	Córdoba		Spain	14004
177	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
178	Hospital Clinico San Carlos	Madrid		Spain	28040
179	Hospital 12 de Octubre	Madrid		Spain	28041
180	Centro Integral Oncológico Clara Campal	Madrid		Spain	28050
181	Hospital Virgen del Rocio	Sevilla		Spain	41013
182	Dnepropetrovsk City Hosp #4	Dnepropetrovsk	UK	Ukraine	49102
183	Donetsk Regional Antitumor Ctr	Donetsk	UK	Ukraine	83092
184	Kirovohrad Regional Oncology Center, Department of Chemotherapy	Kirovohrad	UK	Ukraine	25031
185	National Institute of Cancer, Department of Tumors of Abdominal Cavity and Retroperitoneum	Kyiv	UK	Ukraine	03022
186	Kyiv City Clinical Hospital #10, Center for Hepatic, Bile Duct and Pancreatic Surgery	Kyiv	UK	Ukraine	3039
187	Volyn Regional Oncology Center Department of Oncochemotherapy	Lutsk	UK	Ukraine	43018
188	Lviv Regional Diagnostics and Treatment and Diagnostics Onc Ctr	Lviv	UK	Ukraine	79031
189	O.F. Herbachevskyi Regional Clinical Hospital, Surgery Center	Zhytomyr	UK	Ukraine	10008
190	Kharkov Regional Onc Ctr	Kharkov		Ukraine	61070
191	Kherson Regional Onc Ctr	Kherson		Ukraine	73000
192	Odessa Regional Onc Ctr	Odessa		Ukraine	65055
193	Zaporizhia Medical Academy of Postgraduate Education	Zaporizhia		Ukraine	69096

Sponsors and Collaborators

• Celgene

Investigators

• Principal Investigator: Daniel Von Hoff, MD, Scottsdale Clinical Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chiorean EG, Von Hoff DD, Tabernero J, El-Maraghi R, Ma WW, Reni M, Harris M, Whorf R, Liu H, Li JS, Manax V, Romano A, Lu B, Goldstein D. Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer. Br J Cancer. 2016 Jul 12;115(2):188-94. doi: 10.1038/bjc.2016.185. Epub 2016 Jun 28. Erratum in: Br J Cancer. 2016 Oct 25;115(9):e13.
• Kunzmann V, Ramanathan RK, Goldstein D, Liu H, Ferrara S, Lu B, Renschler MF, Von Hoff DD. Tumor Reduction in Primary and Metastatic Pancreatic Cancer Lesions With nab-Paclitaxel and Gemcitabine: An Exploratory Analysis From a Phase 3 Study. Pancreas. 2017 Feb;46(2):203-208. doi: 10.1097/MPA.0000000000000742.
• Scheithauer W, Ramanathan RK, Moore M, Macarulla T, Goldstein D, Hammel P, Kunzmann V, Liu H, McGovern D, Romano A, Von Hoff DD. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial. J Gastrointest Oncol. 2016 Jun;7(3):469-78. doi: 10.21037/jgo.2016.01.03.
• Tabernero J, Chiorean EG, Infante JR, Hingorani SR, Ganju V, Weekes C, Scheithauer W, Ramanathan RK, Goldstein D, Penenberg DN, Romano A, Ferrara S, Von Hoff DD. Prognostic factors of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer. Oncologist. 2015 Feb;20(2):143-50. doi: 10.1634/theoncologist.2014-0394. Epub 2015 Jan 12.
• Tabernero J, Kunzmann V, Scheithauer W, Reni M, Shiansong Li J, Ferrara S, Djazouli K. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial. Onco Targets Ther. 2017 Feb 2;10:591-596. doi: 10.2147/OTT.S124097. eCollection 2017.
• Tehfe M, Dowden S, Kennecke H, El-Maraghi R, Lesperance B, Couture F, Letourneau R, Liu H, Romano A. nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3 MPACT Trial. Adv Ther. 2016 May;33(5):747-59. doi: 10.1007/s12325-016-0327-4. Epub 2016 Apr 16. Erratum in: Adv Ther. 2016 Nov 24;:.
• Vogel A, Römmler-Zehrer J, Li JS, McGovern D, Romano A, Stahl M. Efficacy and safety profile of nab-paclitaxel plus gemcitabine in patients with metastatic pancreatic cancer treated to disease progression: a subanalysis from a phase 3 trial (MPACT). BMC Cancer. 2016 Oct 21;16(1):817.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00844649
• Other Study ID Numbers: CA046
• First Posted: Feb 16, 2009
• Last Update Posted: Nov 25, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	Participants were randomized in a 1:1 ratio and the randomization was stratified by geographic region (Australia versus Eastern Europe versus Western Europe versus North America), Karnofsky performance status (70 to 80 versus 90 to 100), and by the presence of liver metastases (yes versus no)
Pre-assignment Detail	38 participants were randomized but not treated due to the participants request to withdraw after the randomization results became known. 1 participant was randomized to Gemcitabine and was treated with Albumin-bound paclitaxel ABI-007/Gemcitabine in error and analyzed as treated and included in the intent to treat population (ITT)

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine (Gem)	Gemcitabine (Gem)
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Period Title: Overall Study
STARTED	431	430
Treated Population	421	402
COMPLETED	26	12
NOT COMPLETED	405	418

Baseline Characteristics

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine	Gemcitabine	Total
Arm/Group Description	ABI-007 125 mg/m^2 administered in combination with gemcitabine 1000 mg/m^2 weekly for 3 weeks followed by one week of rest. Albumin-bound paclitaxel (ABI-007)/Gemcitabine : ABI-007 125 mg/m^2 administered in combination with Gemcitabine 1000 mg/m^2 weekly for 3 weeks, Days 1, 8, and 15 followed by one week of rest	Gemcitabine, 1000 mg/m^2 administered weekly for 7 weeks followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks followed by a week of rest (Cycle 2 onward). Gemcitabine : Gemcitabine, 1000 mg/m2 administered weekly for 7 weeks, Day 1 through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks, Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward).	Total of all reporting groups
Overall Participants	431	430	861
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (10.70)	63.0 (9.27)	62.2 (10.04)
Sex: Female, Male (Count of Participants)
Female	186 43.2%	173 40.2%	359 41.7%
Male	245 56.8%	257 59.8%	502 58.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	8 1.9%	9 2.1%	17 2%
Native Hawaiian or Other Pacific Islander	1 0.2%	0 0%	1 0.1%
Black or African American	16 3.7%	16 3.7%	32 3.7%
White	378 87.7%	375 87.2%	753 87.5%
More than one race	25 5.8%	26 6%	51 5.9%
Unknown or Not Reported	3 0.7%	4 0.9%	7 0.8%
Karnofsky Performance Status (KPS) (participants) [Number]
100% = normal, no complaints, no signs of disease	69 16%	69 16%	138 16%
90% = normal activity, few symptoms of disease	179 41.5%	199 46.3%	378 43.9%
80% = normal activity, some symptoms of disease	149 34.6%	128 29.8%	277 32.2%
70% = caring for self, unable to work	30 7%	33 7.7%	63 7.3%
60% = needs help, can manage most tasks	2 0.5%	0 0%	2 0.2%
50% = needs help often and medical care	0 0%	0 0%	0 0%
40% = disabled; requires special care & assistance	0 0%	0 0%	0 0%
30% = severely disabled; death is imminent	0 0%	0 0%	0 0%
20% = hospitalized; requires supportive treatment	0 0%	0 0%	0 0%
10% = Moribund, fatal processes progressing fast	0 0%	0 0%	0 0%
0% = Dead	0 0%	0 0%	0 0%
Pancreatic Primary Tumor Location (participants) [Number]
Head	191 44.3%	180 41.9%	371 43.1%
Body	132 30.6%	136 31.6%	268 31.1%
Tail	105 24.4%	110 25.6%	215 25%
Unknown = not specified	3 0.7%	4 0.9%	7 0.8%
Number of Baseline Lesions (Target + Non-Target) (participants) [Number]
1	1 0.2%	0 0%	1 0.1%
2	32 7.4%	25 5.8%	57 6.6%
3	7 1.6%	7 1.6%	14 1.6%
4	37 8.6%	43 10%	80 9.3%
5	8 1.9%	8 1.9%	16 1.9%
>5	276 64%	262 60.9%	538 62.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time from the date of randomization to the date of death from all causes. Participants who did not die were censored at the last known time the participant was alive. Patient survival was summarized using Kaplan-Meier methods.
Time Frame	From randomization to death; until the data cut off 17 Sept 2012. The maximum time in follow up was 37 months.

Outcome Measure Data

Analysis Population Description

Intent to Treat population (ITT population) consisted of all randomized participants.

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine	Gemcitabine
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Measure Participants	431	430
Median (95% Confidence Interval) [months]	8.5	6.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine, Gemcitabine
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test stratified by randomization strata of geographic region (North America versus Others), Karnofsky performance score (70 to 80 versus 90 to 100), and presence of liver metastasis
	Method	Stratified Log-rank Test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.617 to 0.835
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio of Albumin bound paclitaxel + gemcitabine/gemcitabine alone. The associated hazard ratio and two-sided 95% confidence interval were estimated using a stratified Cox proportional hazard model.

2. Secondary Outcome

Title	Progression-free Survival (PFS) by Independent Radiological Review (IRR)
Description	Progression-free survival was defined as the time from the date of randomization to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurred earlier. Participants who did not have disease progression or had not died were censored at the date of the last tumor assessment, on or prior to the clinical cutoff, and the patient was progression free. If a patient began a new anti-cancer treatment prior to documented disease progression (or death), the patient was censored at the date of last assessment when the patient was documented as progression free prior to the intervention. Patients with two or more consecutive missing response assessments prior to a visit with documented progression (or death) were censored at the last date of tumor assessment when the patient was documented to be progression free. PFS was summarized using Kaplan-Meier methods.
Time Frame	Randomization until disease progression or death from any cause; Until the data cut off of 17 Sept 2012. The maximum time in follow up was 37 months.

Outcome Measure Data

Analysis Population Description

Intent to Treat population (ITT population) consisted of all randomized participants.

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine	Gemcitabine
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Measure Participants	431	430
Median (95% Confidence Interval) [months]	5.5	3.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine, Gemcitabine
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test by randomization strata of geographic region (North America versus Others), Karnofsky performance score (70 to 80 versus 90 to 100), and presence of liver metastasis (yes vs no)
	Method	Stratified Log-rank Test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.69
	Confidence Interval	(2-Sided) 95%; 0.581 to 0.821
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio of Albumin bound paclitaxel + gemcitabine / gemcitabine alone. The associated hazard ratio and two-sided 95% confidence interval were estimated using a stratified Cox proportional hazard model.

3. Secondary Outcome

Title	Percentage of Participants Who Achieved an Objective Confirmed Overall Response by Independent Radiological Review (IRR)
Description	Objective tumor response was summarized as the percentage of participants who achieved a confirmed complete (CR) or partial response (PR) based on an independent blinded radiology assessment of response using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Using RECIST Version 1.0, participants were to achieve either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the investigator assessment of best overall response during study treatment.
Time Frame	Assessment every 4 weeks after initial response; Day 1 to data cut off of 17 Sept 2013; maximum time on study 37 months

Outcome Measure Data

Analysis Population Description

Intent to Treat population (ITT population) consisted of all randomized participants.

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine	Gemcitabine
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Measure Participants	431	430
Number (95% Confidence Interval) [percentage of participants]	23 5.3%	7 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine, Gemcitabine
	Comments	PA+G/PG = response rate ratio of albumin bound paclitaxel + gemcitabine / gemcitabine.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Response Rate Ratio
	Estimated Value	3.19
	Confidence Interval	(2-Sided) 95%; 2.178 to 4.662
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response rate ratio: albumin-bound paclitaxel + gemcitabine /gemcitabine alone

4. Other Pre-specified Outcome

Title	Participants With Treatment Emergent Adverse Events (AE)
Description	A Treatment Emergent Adverse Event (TEAE) is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE.
Time Frame	Study drug initiation through 30 days after the last dose of study drug or EOS, whichever is later; Up to 696 days

Outcome Measure Data

Analysis Population Description

Treated patient population

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine	Gemcitabine
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Measure Participants	421	402
At least 1 AE	417 96.8%	395 91.9%
≥ 1 Treatment related AE (TEAE)	403 93.5%	371 86.3%
At least 1 Serious Adverse Event (SAE)	212 49.2%	172 40%
≥ 1 treatment related SAE	121 28.1%	53 12.3%
≥ 1 Grade (GR) 3/4 AE	370 85.8%	298 69.3%
≥ 1 Grade 3 or higher AE	374 86.8%	303 70.5%
≥ 1 AE leading to stopping treatment	149 34.6%	95 22.1%
≥ 1 AE leading to death	18 4.2%	18 4.2%
≥ 1 AE leading to dose reduction of ABI-007 or Gem	209 48.5%	125 29.1%
≥ 1 AE related dose interruption of ABI-007 or Gem	11 2.6%	10 2.3%
≥ 1 AE related dose delay of ABI-007 or Gem	276 64%	192 44.7%

5. Other Pre-specified Outcome

Title	Number of Participants With Dose Reductions
Description	The number of participants with dose reductions occurring during the treatment period. Dose reductions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.
Time Frame	Maximum time on treatment was 666 days

Outcome Measure Data

Analysis Population Description

Treated Population

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine (Gem)	Gemcitabine (Gem)
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Measure Participants	421	402
At least 1 alumbin bound paclitaxel dose reduction	172 39.9%	0 0%
At least 1 Gemcitabine dose reduction	198 45.9%	132 30.7%

6. Other Pre-specified Outcome

Title	Number of Participants With Dose Interruptions
Description	The number of participants with dose interruptions experienced by participants that occurred during the treatment period. Dose interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.
Time Frame	Maximum time on treatment was 666 days

Outcome Measure Data

Analysis Population Description

Safety population, includes participants who received at least one study treatment

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine	Gemcitabine
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Measure Participants	421	402
≥ 1 Albumin-bound paclitaxel dose interruption	2 0.5%	0 0%
At least 1 Gemcitabine dose interruption	8 1.9%	9 2.1%

7. Other Pre-specified Outcome

Title	Number of Participants With Dose Delays/Doses Not Given
Description	The number of dose delays or doses not given experienced by participants during the treatment period. Dose delays are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities. Treatment delays of no longer than 21 days allowed participants to recover from acute toxicity, otherwise participants were discontinued from further treatment except in the event of peripheral neuropathy.
Time Frame	Up to 666 days

Outcome Measure Data

Analysis Population Description

Treated Population

Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine	Gemcitabine
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest	Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
Measure Participants	421	402
At least 1 ABI-007 dose delay/Not given	300	0
At least ≥ 1 Gem dose delay/Not given	295	230

Adverse Events

Time Frame	Day 1 up to 30 days after the last dose (a maximum of 666 days)
Arm/Group Title	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine		Gemcitabine
Arm/Group Description	Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest		Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)
All Cause Mortality
	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine		Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine		Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	212/421 (50.4%)		172/402 (42.8%)
Blood and lymphatic system disorders
Febrile neutropenia	11/421 (2.6%)		2/402 (0.5%)
Anaemia	9/421 (2.1%)		2/402 (0.5%)
Neutropenia	4/421 (1%)		1/402 (0.2%)
Pancytopenia	3/421 (0.7%)		0/402 (0%)
Haemolytic uraemic syndrome	2/421 (0.5%)		1/402 (0.2%)
Leukopenia	2/421 (0.5%)		0/402 (0%)
Haemorrhagic anaemia	1/421 (0.2%)		0/402 (0%)
Thrombocytopenia	1/421 (0.2%)		3/402 (0.7%)
Thrombotic thrombocytopenic purpura	1/421 (0.2%)		0/402 (0%)
Leukocytosis	0/421 (0%)		2/402 (0.5%)
Cardiac disorders
Cardiac failure congestive	3/421 (0.7%)		1/402 (0.2%)
Atrial Fibrillation	2/421 (0.5%)		3/402 (0.7%)
Myocardial Infarction	2/421 (0.5%)		1/402 (0.2%)
Acute coronary syndrome	1/421 (0.2%)		0/402 (0%)
Atrial tachycardia	1/421 (0.2%)		0/402 (0%)
Cardiac arrest	1/421 (0.2%)		3/402 (0.7%)
Cardiogenic shock	1/421 (0.2%)		0/402 (0%)
Angina unstable	0/421 (0%)		1/402 (0.2%)
Cardiopulmonary Failure	0/421 (0%)		1/402 (0.2%)
Myocardial ischaemia	0/421 (0%)		1/402 (0.2%)
Pericardial effusion	0/421 (0%)		1/402 (0.2%)
Eye disorders
Visual acuity reduced	1/421 (0.2%)		0/402 (0%)
Gastrointestinal disorders
Vomiting	18/421 (4.3%)		12/402 (3%)
Abdominal Pain	11/421 (2.6%)		10/402 (2.5%)
Nausea	11/421 (2.6%)		8/402 (2%)
Diarrhoea	9/421 (2.1%)		3/402 (0.7%)
Ascites	4/421 (1%)		5/402 (1.2%)
Intestinal obstruction	4/421 (1%)		1/402 (0.2%)
Small intestinal obstruction	4/421 (1%)		1/402 (0.2%)
Duodenal Obstruction	3/421 (0.7%)		2/402 (0.5%)
Colitis	2/421 (0.5%)		0/402 (0%)
Ileus	2/421 (0.5%)		0/402 (0%)
Pancreatitis	2/421 (0.5%)		0/402 (0%)
Upper gastrointestinal haemorrhage	2/421 (0.5%)		0/402 (0%)
Abdominal pain upper	1/421 (0.2%)		0/402 (0%)
Colitis Ischaemic	1/421 (0.2%)		1/402 (0.2%)
Faecaloma	1/421 (0.2%)		0/402 (0%)
Gastrooesophageal reflux disease	1/421 (0.2%)		1/402 (0.2%)
Impaired gastric empyting	1/421 (0.2%)		0/402 (0%)
Intestinal perforation	1/421 (0.2%)		1/402 (0.2%)
Melaena	1/421 (0.2%)		0/402 (0%)
Mesenteric vein thrombosis	1/421 (0.2%)		0/402 (0%)
Obstruction gastric	1/421 (0.2%)		1/402 (0.2%)
Oesophageal varices haemorrhage	1/421 (0.2%)		0/402 (0%)
Pancreatic cyst rupture	1/421 (0.2%)		0/402 (0%)
Pancreatic pseudocyst	1/421 (0.2%)		0/402 (0%)
Regurgitation	1/421 (0.2%)		0/402 (0%)
Colitis microscopic	0/421 (0%)		1/402 (0.2%)
Haematemesis	0/421 (0%)		1/402 (0.2%)
Large Intestine perforation	0/421 (0%)		1/402 (0.2%)
Pancreatic haemorrhage	0/421 (0%)		1/402 (0.2%)
Small intestinal haemorrhage	0/421 (0%)		1/402 (0.2%)
Splenic artery aneurysm	0/421 (0%)		1/402 (0.2%)
Constipation	5/421 (1.2%)		6/402 (1.5%)
Duodenal stenosis	0/421 (0%)		1/402 (0.2%)
Gastric haemorrhage	0/421 (0%)		1/402 (0.2%)
Gastrointestinal haemorrhage	0/421 (0%)		6/402 (1.5%)
General disorders
Pyrexia	27/421 (6.4%)		9/402 (2.2%)
Oedema peripheral	6/421 (1.4%)		3/402 (0.7%)
Asthenia	3/421 (0.7%)		5/402 (1.2%)
Fatigue	3/421 (0.7%)		2/402 (0.5%)
General physical health deterioration	2/421 (0.5%)		1/402 (0.2%)
Chills	1/421 (0.2%)		1/402 (0.2%)
Mucosal inflammation	1/421 (0.2%)		0/402 (0%)
Multi-organ failure	1/421 (0.2%)		1/402 (0.2%)
Pain	1/421 (0.2%)		2/402 (0.5%)
Systemic inflammatory response syndrome	1/421 (0.2%)		0/402 (0%)
Device occlusion	0/421 (0%)		2/402 (0.5%)
Face oedema	0/421 (0%)		1/402 (0.2%)
Localised oedema	0/421 (0%)		3/402 (0.7%)
Non-cardiac chest pain	0/421 (0%)		1/402 (0.2%)
Sudden death	0/421 (0%)		2/402 (0.5%)
Adverse drug reaction	1/421 (0.2%)		0/402 (0%)
Generalized oedema	0/421 (0%)		1/402 (0.2%)
Hepatobiliary disorders
Cholangitis	10/421 (2.4%)		5/402 (1.2%)
Bile duct obstruction	4/421 (1%)		3/402 (0.7%)
Jaundice	4/421 (1%)		1/402 (0.2%)
Hyperbilirubinaemia	2/421 (0.5%)		1/402 (0.2%)
Cholecystitis	1/421 (0.2%)		0/402 (0%)
Cholecystitis acute	1/421 (0.2%)		1/402 (0.2%)
Hepatic function abnormal	1/421 (0.2%)		0/402 (0%)
Hepatotoxicity	1/421 (0.2%)		0/402 (0%)
Cholangitis acute	0/421 (0%)		1/402 (0.2%)
Gallbladder perforation	0/421 (0%)		1/402 (0.2%)
Hepatic cirrhosis	0/421 (0%)		1/402 (0.2%)
Hepatic failure	0/421 (0%)		1/402 (0.2%)
Jaundice cholestatic	4/421 (1%)		3/402 (0.7%)
Infections and infestations
Pneumonia	17/421 (4%)		11/402 (2.7%)
Cellulitis	8/421 (1.9%)		5/402 (1.2%)
Sepsis	5/421 (1.2%)		5/402 (1.2%)
Septic Shock	4/421 (1%)		5/402 (1.2%)
Bacterial Sepsis	3/421 (0.7%)		0/402 (0%)
Lower Respiratory tract infection	3/421 (0.7%)		2/402 (0.5%)
Catheter site infection	2/421 (0.5%)		0/402 (0%)
Clostridium difficile colitis	2/421 (0.5%)		1/402 (0.2%)
Klebsiella bacteraemia	2/421 (0.5%)		0/402 (0%)
Liver Abscess	2/421 (0.5%)		3/402 (0.7%)
Neutropenic sepsis	2/421 (0.5%)		0/402 (0%)
Bacteraemia	1/421 (0.2%)		0/402 (0%)
Biliary sepsis	1/421 (0.2%)		0/402 (0%)
Bronchitis	1/421 (0.2%)		0/402 (0%)
Cellulitis of male external genital organ	1/421 (0.2%)		0/402 (0%)
Clostridial infection	1/421 (0.2%)		1/402 (0.2%)
Device related infection	1/421 (0.2%)		0/402 (0%)
Escherichia bacteraemia	1/421 (0.2%)		0/402 (0%)
Gastroenteritis	1/421 (0.2%)		1/402 (0.2%)
Gastroenteritis viral	1/421 (0.2%)		0/402 (0%)
Infection	1/421 (0.2%)		0/402 (0%)
Laryngitis	1/421 (0.2%)		0/402 (0%)
Lung Infection	1/421 (0.2%)		0/402 (0%)
Oral Candidiasis	1/421 (0.2%)		0/402 (0%)
Perirectal abscess	1/421 (0.2%)		0/402 (0%)
Pneumonia bacterial	1/421 (0.2%)		0/402 (0%)
Pneumonia primary atypical	1/421 (0.2%)		0/402 (0%)
Postoperative wound infection	1/421 (0.2%)		0/402 (0%)
Pseudomonal sepsis	1/421 (0.2%)		0/402 (0%)
Skin Infection	1/421 (0.2%)		0/402 (0%)
Tooth abscess	1/421 (0.2%)		0/402 (0%)
Tooth Infection	1/421 (0.2%)		0/402 (0%)
Urosepsis	1/421 (0.2%)		0/402 (0%)
Biliary abscess	0/421 (0%)		1/402 (0.2%)
Breast cellulitis	0/421 (0%)		1/402 (0.2%)
Gastroenteritis clostridial	0/421 (0%)		1/402 (0.2%)
Infected dermal cyst	0/421 (0%)		1/402 (0.2%)
Klebsiella sepsis	0/421 (0%)		1/402 (0.2%)
Lung infection pseudomonal	0/421 (0%)		1/402 (0.2%)
Streptococcal bacteraemia	0/421 (0%)		1/402 (0.2%)
Perihepatic abscess	1/421 (0.2%)		0/402 (0%)
Injury, poisoning and procedural complications
Urinary Tract Infection	6/421 (1.4%)		1/402 (0.2%)
Accidental overdose	1/421 (0.2%)		1/402 (0.2%)
Fall	1/421 (0.2%)		1/402 (0.2%)
Post procedural haemorrhage	1/421 (0.2%)		0/402 (0%)
Subdural haematoma	1/421 (0.2%)		0/402 (0%)
Cervical vertebral fracture	0/421 (0%)		1/402 (0.2%)
In-stent coronary artery restenosis	0/421 (0%)		1/402 (0.2%)
Investigations
Liver Function test abnormal	2/421 (0.5%)		0/402 (0%)
Alanine aminotransferase increased	1/421 (0.2%)		1/402 (0.2%)
Blood alkaline phosphatase increased	1/421 (0.2%)		0/402 (0%)
Gamma-glutamyltransferase increased	1/421 (0.2%)		0/402 (0%)
Haemoglobulin decreased	1/421 (0.2%)		0/402 (0%)
Platelet count decreased	1/421 (0.2%)		0/402 (0%)
Transaminases increased	1/421 (0.2%)		0/402 (0%)
Aspartate aminotransferase increased	0/421 (0%)		1/402 (0.2%)
Heart rate increased	0/421 (0%)		1/402 (0.2%)
Neutrophil count decreased	0/421 (0%)		1/402 (0.2%)
Weight decreased	0/421 (0%)		1/402 (0.2%)
Blood bilirubin increased	1/421 (0.2%)		1/402 (0.2%)
Metabolism and nutrition disorders
Dehyration	20/421 (4.8%)		12/402 (3%)
Decreased Appetite	5/421 (1.2%)		0/402 (0%)
Hyperkalaemia	0/421 (0%)		3/402 (0.7%)
Hyponatraemia	2/421 (0.5%)		1/402 (0.2%)
Diabetic ketoacidosis	1/421 (0.2%)		1/402 (0.2%)
Failure to thrive	1/421 (0.2%)		0/402 (0%)
Hyperglycaemia	1/421 (0.2%)		0/402 (0%)
Hypoglycaemia	1/421 (0.2%)		3/402 (0.7%)
Hypoalbuminaemia	0/421 (0%)		1/402 (0.2%)
Hypovolaemia	0/421 (0%)		1/402 (0.2%)
Pseudohyponatraemia	0/421 (0%)		1/402 (0.2%)
Hypokalaemia	2/421 (0.5%)		0/402 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/421 (0.2%)		0/402 (0%)
Musculoskeletal pain	1/421 (0.2%)		1/402 (0.2%)
Musculoskeletal chest pain	1/421 (0.2%)		0/402 (0%)
Back pain	0/421 (0%)		1/402 (0.2%)
Joint swelling	0/421 (0%)		1/402 (0.2%)
Muscular weakness	0/421 (0%)		1/402 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign anorectal neoplasm	1/421 (0.2%)		0/402 (0%)
Malignant ascites	1/421 (0.2%)		0/402 (0%)
Metastatic pain	1/421 (0.2%)		0/402 (0%)
Tumour associated fever	1/421 (0.2%)		0/402 (0%)
Lymphangiosis carcinomatosa	0/421 (0%)		1/402 (0.2%)
Meningioma benign	0/421 (0%)		1/402 (0.2%)
Pancreatic carcinoma metastatic	0/421 (0%)		1/402 (0.2%)
Nervous system disorders
Cerebral ischaemia	2/421 (0.5%)		2/402 (0.5%)
Peripheral motor neuropathy	2/421 (0.5%)		0/402 (0%)
Autonomic nervous system imbalance	1/421 (0.2%)		0/402 (0%)
Cerebral infarction	1/421 (0.2%)		0/402 (0%)
Cerebrovascular accident	1/421 (0.2%)		5/402 (1.2%)
Dizziness	1/421 (0.2%)		0/402 (0%)
Headache	1/421 (0.2%)		0/402 (0%)
Hepatic encephalopathy	1/421 (0.2%)		0/402 (0%)
Ischaemic cerebral infarction	1/421 (0.2%)		0/402 (0%)
Neurotoxicity	1/421 (0.2%)		0/402 (0%)
Syncope	1/421 (0.2%)		2/402 (0.5%)
Ataxia	0/421 (0%)		1/402 (0.2%)
Cognitive disorder	0/421 (0%)		1/402 (0.2%)
Depressed level of consciousness	0/421 (0%)		1/402 (0.2%)
Hemiparesis	0/421 (0%)		1/402 (0.2%)
Hypoglycaemic coma	0/421 (0%)		1/402 (0.2%)
Lethargy	0/421 (0%)		1/402 (0.2%)
Optic neuritis	0/421 (0%)		1/402 (0.2%)
Presyncope	0/421 (0%)		1/402 (0.2%)
Transient ischaemic attack	0/421 (0%)		1/402 (0.2%)
Psychiatric disorders
Mental status changes	2/421 (0.5%)		2/402 (0.5%)
Confusional state	1/421 (0.2%)		0/402 (0%)
Depression	1/421 (0.2%)		0/402 (0%)
Hallucination	1/421 (0.2%)		0/402 (0%)
Suicidal ideation	1/421 (0.2%)		0/402 (0%)
Anxiety	0/421 (0%)		2/402 (0.5%)
Biopolar I disorder	0/421 (0%)		1/402 (0.2%)
Delirium	0/421 (0%)		1/402 (0.2%)
Renal and urinary disorders
Renal Failure	2/421 (0.5%)		3/402 (0.7%)
Renal failure acute	2/421 (0.5%)		4/402 (1%)
Renal colic	1/421 (0.2%)		0/402 (0%)
Ureteric obstruction	1/421 (0.2%)		0/402 (0%)
Haematuria	0/421 (0%)		1/402 (0.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	13/421 (3.1%)		20/402 (5%)
Pleural effusion	7/421 (1.7%)		5/402 (1.2%)
Dyspnoea	5/421 (1.2%)		2/402 (0.5%)
Interstitial lung disease	4/421 (1%)		2/402 (0.5%)
Pneumonitis	4/421 (1%)		1/402 (0.2%)
Acute respiratory distress syndrome	1/421 (0.2%)		0/402 (0%)
Diffuse alveolar damage	1/421 (0.2%)		0/402 (0%)
Epistaxis	1/421 (0.2%)		0/402 (0%)
Pulmonary alveolar haemorrhage	1/421 (0.2%)		0/402 (0%)
Acute respiratory failure	0/421 (0%)		1/402 (0.2%)
Hypoxia	0/421 (0%)		1/402 (0.2%)
Pneumothorax	0/421 (0%)		1/402 (0.2%)
Skin and subcutaneous tissue disorders
Erythema	1/421 (0.2%)		0/402 (0%)
Rash maculo-papular	1/421 (0.2%)		0/402 (0%)
Vascular disorders
Deep vein thrombosis	9/421 (2.1%)		12/402 (3%)
Capilary leak syndrome	1/421 (0.2%)		0/402 (0%)
Hypotension	1/421 (0.2%)		1/402 (0.2%)
Labile hypertension	1/421 (0.2%)		0/402 (0%)
Malignant hypertension	1/421 (0.2%)		0/402 (0%)
Thrombosis	1/421 (0.2%)		1/402 (0.2%)
Arterial thrombosis limb	0/421 (0%)		2/402 (0.5%)
Hypovolaemic shock	0/421 (0%)		1/402 (0.2%)
Lymphoedema	0/421 (0%)		1/402 (0.2%)
Orthostatic hypotension	0/421 (0%)		1/402 (0.2%)
Phlebitis	0/421 (0%)		1/402 (0.2%)
Subclavian vein thrombosis	0/421 (0%)		1/402 (0.2%)
Venous stenosis	0/421 (0%)		1/402 (0.2%)
Other (Not Including Serious) Adverse Events
	Albumin-bound Paclitaxel (ABI-007)/Gemcitabine		Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	412/421 (97.9%)		392/402 (97.5%)
Blood and lymphatic system disorders
Anaemia	175/421 (41.6%)		131/402 (32.6%)
Neutropenia	172/421 (40.9%)		122/402 (30.3%)
Thrombocytopenia	127/421 (30.2%)		115/402 (28.6%)
Leukopenia	58/421 (13.8%)		39/402 (9.7%)
Gastrointestinal disorders
Nausea	223/421 (53%)		189/402 (47%)
Diarrhoea	182/421 (43.2%)		94/402 (23.4%)
Vomiting	145/421 (34.4%)		107/402 (26.6%)
Constipation	122/421 (29%)		111/402 (27.6%)
Abdominal Pain	92/421 (21.9%)		87/402 (21.6%)
Abdominal pain upper	42/421 (10%)		28/402 (7%)
Dyspepsia	34/421 (8.1%)		28/402 (7%)
Stomatitis	31/421 (7.4%)		14/402 (3.5%)
Abdominal distension	16/421 (3.8%)		29/402 (7.2%)
Ascites	15/421 (3.6%)		26/402 (6.5%)
General disorders
Fatigue	247/421 (58.7%)		183/402 (45.5%)
Oedema peripheral	194/421 (46.1%)		123/402 (30.6%)
Pyrexia	160/421 (38%)		111/402 (27.6%)
Asthenia	77/421 (18.3%)		51/402 (12.7%)
Chills	48/421 (11.4%)		34/402 (8.5%)
Mucosal inflammation	42/421 (10%)		16/402 (4%)
Pain	24/421 (5.7%)		8/402 (2%)
Infections and infestations
Urinary tract infection	37/421 (8.8%)		14/402 (3.5%)
Oral candidiasis	33/421 (7.8%)		15/402 (3.7%)
Cellulitis	25/421 (5.9%)		16/402 (4%)
Investigations
Weight decreased	57/421 (13.5%)		47/402 (11.7%)
Alanine aminotransferase increased	45/421 (10.7%)		36/402 (9%)
Haemoglobin decreased	41/421 (9.7%)		29/402 (7.2%)
Aspartate aminotransferase increased	38/421 (9%)		35/402 (8.7%)
Platelet count decreased	33/421 (7.8%)		25/402 (6.2%)
Neutrophil count decreased	26/421 (6.2%)		19/402 (4.7%)
Blood alkaline phosphatase increased	21/421 (5%)		30/402 (7.5%)
Metabolism and nutrition disorders
Decreased appetite	149/421 (35.4%)		104/402 (25.9%)
Dehydration	75/421 (17.8%)		33/402 (8.2%)
Hypokalemia	50/421 (11.9%)		28/402 (7%)
Hypoalbuminaemia	25/421 (5.9%)		18/402 (4.5%)
Hyperglycaemia	22/421 (5.2%)		18/402 (4.5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	48/421 (11.4%)		24/402 (6%)
Arthralgia	46/421 (10.9%)		13/402 (3.2%)
Myalgia	44/421 (10.5%)		15/402 (3.7%)
Back Pain	41/421 (9.7%)		40/402 (10%)
Bone pain	24/421 (5.7%)		8/402 (2%)
Nervous system disorders
Neuropathy peripheral	116/421 (27.6%)		11/402 (2.7%)
Peripheral sensory neuropathy	107/421 (25.4%)		17/402 (4.2%)
Dysgeusia	68/421 (16.2%)		33/402 (8.2%)
Headache	60/421 (14.3%)		38/402 (9.5%)
Dizziness	47/421 (11.2%)		34/402 (8.5%)
Psychiatric disorders
Insomnia	64/421 (15.2%)		46/402 (11.4%)
Depression	50/421 (11.9%)		24/402 (6%)
Anxiety	35/421 (8.3%)		43/402 (10.7%)
Respiratory, thoracic and mediastinal disorders
Cough	72/421 (17.1%)		30/402 (7.5%)
Dyspnoea	71/421 (16.9%)		61/402 (15.2%)
Epistaxis	64/421 (15.2%)		14/402 (3.5%)
Dyspnoea exertional	24/421 (5.7%)		13/402 (3.2%)
Skin and subcutaneous tissue disorders
Alopecia	212/421 (50.4%)		21/402 (5.2%)
Rash	117/421 (27.8%)		39/402 (9.7%)
Pruritis	34/421 (8.1%)		20/402 (5%)
Dry Skin	24/421 (5.7%)		9/402 (2.2%)
Erythema	24/421 (5.7%)		13/402 (3.2%)
Vascular disorders
Hypotension	38/421 (9%)		26/402 (6.5%)
Deep vein thrombosis	30/421 (7.1%)		22/402 (5.5%)

Limitations/Caveats

[Not Specified]

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

Authorship/contents of any publication is determined by site and provides sponsor a publication prior to submission. Sponsor has 60 days to review and avoid editorial changes but may request site delete confidential data. If publication contains patentable matter, site agrees to delay publication for 60 days. If study is part of multicenter protocol, site agrees not to independently publish. If multicenter publication is not forthcoming in 18 months after study end, site may proceed accordingly.