SNAP: Schedules of Nab-Paclitaxel in Metastatic Breast Cancer

• Sponsor: ETOP IBCSG Partners Foundation (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01746225
• Collaborator: Breast International Group (Other)
• Enrollment: 258
• Locations: 41
• Arms: 3
• Duration (Months): 120
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Longer first line chemotherapy duration has recently been associated with a modest, but significant improvement in overall survival and a clinically meaningful and statistically significant improvement in progression-free survival, in metastatic breast cancer patients. Prolonging chemotherapy until disease progression, however, must be weighed against the detrimental effects of continuous chemotherapy delivery. The SNAP trial seeks to improve the tolerability of prolonged chemotherapy administration strategy by studying alternative treatment schedules, while preserving and possibly improving treatment efficacy in this disease setting.

The availability of a new nanoparticle albumin-bound taxane, nab-Paclitaxel (Abraxane®), represents an opportunity to test this hypothesis. Nab-Paclitaxel has been developed in an attempt to reduce the toxicity associated with standard taxane administration (caused by the use of chemical solvents) while increasing antitumor efficacy.

The SNAP randomized phase II trial evaluates three schedules of nab-Paclitaxel as prolonged chemotherapy administration strategy. Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms are worthy of further investigation.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breastcancer	Drug: nab-Paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 258 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study Evaluating Different Schedules of Nab-Paclitaxel in Metastatic Breast Cancer (SNAP Trial)
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: May 1, 2016
• Anticipated Study Completion Date: Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: nab-Paclitaxel 150 mg/m2 days 1,15 Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Drug: nab-Paclitaxel; Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations); Other Names: Abraxane
Experimental: B: nab-Paclitaxel 100 mg/m2 days 1,8,15 Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Drug: nab-Paclitaxel; Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations); Other Names: Abraxane
Experimental: C: nab-Paclitaxel 75 mg/m2 days 1,8,15,22 Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Drug: nab-Paclitaxel; Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations); Other Names: Abraxane

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Reported after 18.2 months median follow-up since randomization]

   Time from randomization until objective disease progression [progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions] or death, whichever occurs first. For patients without progression, follow-up was censored at the date of last disease assessment without progression, unless death occurred within a short period of time (12 weeks) following the date last known progression-free, in which case the death was counted as a PFS event.

Secondary Outcome Measures

1. Feasibility of Treatment: Number of Participants Completed Treatment According to the Protocol for at Least 24 Weeks [Baseline to 24 weeks follow-up]

   Whether or not the patient completed treatment according to the protocol for at least 24 weeks. Patients who progressed within 24 weeks were considered as not completing.

2. Disease Control: Overall Response of Stable Disease for a Duration of ≥24 Weeks [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months]

   Overall response of stable disease (or non-CR/non-PD for patients with non-measurable disease) for a duration of ≥24 weeks, or better (i.e., partial or complete response) according to RECIST criteria [Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.]

3. Best Overall Response [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months]

   Best response according to RECIST 1.1 criteria [assessed by MRI] recorded from the start of treatment across all time points until end of study treatment. Confirmation of partial or complete response by an additional scan was not requested in this trial.

4. Overall Survival [Reported after 18.2 months median follow-up since randomization]

   Time from randomization until death from any cause, or censored at date last known alive

5. Changes in Physical Well-being (Change From Day 1 of Cycle 4 to Day 1 of Cycle 6) [Assessed from day 1 of cycle 4 through day 1 of cycle 12]

   Primary quality of life=physical well being; endpoint based on the GLQ 8. The indicator was in Linear Analogue Self-Assessment (LASA) format ranging 0-100 (0=as bad as it can be, 100=as good as it can be).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed HER2-negative metastatic (stage IV) breast cancer.

• Measurable or non-measurable, but radiologically evaluable, disease according to RECIST 1.1 criteria.

• Female aged 18 years or older.

• Life expectancy > 3 months.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

• Either ER-positive or ER-negative disease. Patients with ER-positive disease must be endocrine resistant, defined as having failed at least one prior endocrine therapy for breast cancer, or must be candidates for first-line chemotherapy.

• If previously treated with a taxane or anthracycline in the neoadjuvant or adjuvant setting, the period from end of treatment to disease recurrence must have been > 12 months (> 365 days).

• Radiation therapy, if given and regardless of site, must be completed at least 2 weeks prior to randomization.

• Normal hematologic status.

• Normal renal function.

• Normal liver function.

• Normal cardiac function.

• Women of childbearing potential: documented negative pregnancy test within 2 weeks prior to randomization, and acceptable birth control during the duration of the trial therapy and for a period of 6 months following the last administration of study drug.

• Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization.

• Completed baseline Quality of Life Form.

• The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.

• Availability of an formalin fixed paraffin embedded (FFPE) block from the primary tumor (breast lesion) for submission to central pathology review and for translational research.

• Written consent to pathology material submission, signed and dated by the patient and the Investigator prior to randomization.

Exclusion Criteria:

• Any prior chemotherapy for metastatic breast cancer.

• Presence of central nervous system (CNS) metastasis.

• Peripheral neuropathy grade 2 or higher (CTCAE version 4).

• Significant uncontrolled cardiac disease (i.e. unstable angina, recent myocardial infarction within prior 6 months), patients classified as having a New York Heart Association (NYHA) class III or IV congestive heart failure.

• Pregnant or lactating.

• Prior history of non-breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder).

• Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol.

• Contraindications or known hypersensitivity to the study medication or excipients.

• The use of any anti-cancer investigational agents within 30 days prior to expected start of trial treatment.

• Inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHR de la Citadelle, Oncology-Haematology Unit	Liège		Belgium	4000
2	CHU Sart Tilman, Medical Oncology	Liège		Belgium	4000
3	Centre Hospitalier Peltzer-La Tourelle, Department of Clinical Cancerology	Verviers		Belgium	4800
4	Bon Secours	Cork		Ireland
5	Cork University Hospital	Cork		Ireland
6	Beaumont Hospital	Dublin		Ireland
7	Mater Misericordiae University Hospital	Dublin		Ireland
8	Mater Private Hospital	Dublin		Ireland
9	St James's Hospital	Dublin		Ireland
10	St Vincent's University Hospital	Dublin		Ireland
11	University Hospital Galway	Galway		Ireland
12	Mid-Western Regional Hospital	Limerick		Ireland
13	Waterford Regional Hospital	Waterford		Ireland
14	Azienda Ospedaliera SS Antonio e Biagio	Alessandria		Italy	15121
15	Ospedale degli Infermi	Biella		Italy	13900
16	IRCCS MultiMedica	Castellanza		Italy	21053
17	E.O. Ospedali Galliera	Genova		Italy	16128
18	Istituto Europeo di Oncologia (IEO)	Milano		Italy
19	Uo Medicina Ocologica Ospedale Di Carpri e Mirandola, Azienda USL di Modena	Modena		Italy	41012
20	Fondazione Salvatore Maugeri	Pavia		Italy	27100
21	U.O. Oncologia, AUSL Rimini	Rimini		Italy	47923
22	Universita degli Studi di Roma La Sapienza	Roma		Italy	00161
23	Azienda Osp. Universitaria di Udine	Udine		Italy	33100
24	Ospedale di Circolo e Fondatione Macchi	Varese		Italy	21100
25	Institute of Oncology	Ljubljana		Slovenia	1000
26	Hospital Universitari Vall D'Hebron	Barcelona		Spain
27	Consorcop Hospitalario Provincial De Castellon	Castelló		Spain	12002
28	Hospital Universitari Arnau De Vilanova De Lleida	Lleida		Spain	25198
29	Hospital Universitari Sant Joan De Reus	Tarragona		Spain	43204
30	Hospital Universitario Lozano Blesa De Zaragoza	Zaragoza		Spain	50009
31	Kantonsspital Aarau	Aarau		Switzerland	5001
32	Universitätsspital Basel	Basel		Switzerland	4031
33	Instituto Oncologico della Svizzera Italiana	Bellinzona		Switzerland	6500
34	Universitätsspital/ Inselspital Bern	Bern		Switzerland	3011
35	Spitalzentrum Biel	Biel		Switzerland	2501
36	Kantonsspital Graubünden	Chur		Switzerland	7000
37	Kantonsspital Baselland	Liestal		Switzerland	4410
38	Luzerner Kantonsspital	Luzern		Switzerland	6000
39	Kantonsspital St. Gallen	St. Gallen		Switzerland	9007
40	Onkologiezentrum Thun-Berner Oberland	Thun		Switzerland	3600
41	Kantonsspital Winterthur	Winterthur		Switzerland	8401

Sponsors and Collaborators

• ETOP IBCSG Partners Foundation
• Breast International Group

Investigators

• Study Chair: Alessandra Gennari, MD, Division of Medical Oncology, E.O. Galliera, Genoa, Italy
• Study Chair: Guy Jerusalem, MD, PhD, CHU Sart Tilman and University of Liège, Liège, Belgium

Study Documents (Full-Text)

• Study Protocol - Jan 6, 2015
• Statistical Analysis Plan - Mar 1, 2016

More Information

Publications

• Andre F, Slimane K, Bachelot T, Dunant A, Namer M, Barrelier A, Kabbaj O, Spano JP, Marsiglia H, Rouzier R, Delaloge S, Spielmann M. Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol. 2004 Aug 15;22(16):3302-8.
• Chia SK, Speers CH, D'yachkova Y, Kang A, Malfair-Taylor S, Barnett J, Coldman A, Gelmon KA, O'reilly SE, Olivotto IA. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Sep 1;110(5):973-9.
• Dawood S, Broglio K, Gonzalez-Angulo AM, Buzdar AU, Hortobagyi GN, Giordano SH. Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol. 2008 Oct 20;26(30):4891-8. doi: 10.1200/JCO.2007.14.1168. Epub 2008 Aug 25.
• Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer. 2005 Oct 15;104(8):1742-50.

• Responsible Party: ETOP IBCSG Partners Foundation
• ClinicalTrials.gov Identifier: NCT01746225
• Other Study ID Numbers: IBCSG 42-12 / BIG 2-12; 2012-003058-10
• First Posted: Dec 10, 2012
• Last Update Posted: Mar 2, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by ETOP IBCSG Partners Foundation: Metastatic; Breast; Cancer; HER2-negative Stage IV; No previous chemotherapy
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel

Study Results

Participant Flow

Recruitment Details	255 patients were randomized between 16April2013 and 7August2015 at 35 centers in 5 countries.

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Period Title: Overall Study
STARTED	83	86	86
COMPLETED	43	40	43
NOT COMPLETED	40	46	43

Baseline Characteristics

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22	Total
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m². nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations)	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m². nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations)	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m². nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations)	Total of all reporting groups
Overall Participants	83	86	86	255
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	58	56	60	58
Sex: Female, Male (Count of Participants)
Female	83 100%	86 100%	86 100%	255 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	83 100%	85 98.8%	85 98.8%	253 99.2%
Asian	0 0%	1 1.2%	1 1.2%	2 0.8%
Region of Enrollment (participants) [Number]
Belgium	10 12%	10 11.6%	11 12.8%	33 12.9%
Ireland	21 25.3%	22 25.6%	18 20.9%	61 23.9%
Italy	12 14.5%	16 18.6%	12 14%	40 15.7%
Slovenia	3 3.6%	1 1.2%	3 3.5%	7 2.7%
Switzerland	20 24.1%	25 29.1%	29 33.7%	75 29.4%
Spain	17 20.5%	12 14%	13 15.1%	42 16.5%
ER Status (Count of Participants)
Positive	72 86.7%	69 80.2%	69 80.2%	210 82.4%
Negative	11 13.3%	17 19.8%	17 19.8%	45 17.6%
Prior Taxanes (Count of Participants)
Yes	26 31.3%	28 32.6%	26 30.2%	80 31.4%
No	57 68.7%	58 67.4%	60 69.8%	175 68.6%
Type of Radiologically Evaluable Disease (Count of Participants)
Measurable	68 81.9%	73 84.9%	69 80.2%	210 82.4%
Non-measurable only	15 18.1%	13 15.1%	17 19.8%	45 17.6%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Time from randomization until objective disease progression [progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions] or death, whichever occurs first. For patients without progression, follow-up was censored at the date of last disease assessment without progression, unless death occurred within a short period of time (12 weeks) following the date last known progression-free, in which case the death was counted as a PFS event.
Time Frame	Reported after 18.2 months median follow-up since randomization

Outcome Measure Data

Analysis Population Description

Intention-to-treat population

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Measure Participants	83	86	86
Median (90% Confidence Interval) [months]	7.9	9.0	8.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Nab-Paclitaxel 150 mg/m2 Days 1,15
	Comments	For each arm separately, PFS was compared to the historic PFS of first-line docetaxel using a one-sample one-sided log-rank test, of the null hypothesis, H0: median PFS≤7 months vs. H1: median PFS>7 months.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments	Not adjusted for multiple comparisons; One-sided .05 alpha-level test
	Method	Log Rank
	Comments	One-sided test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15
	Comments	For each arm separately, PFS was compared to the historic PFS of first-line docetaxel using a one-sample one-sided log-rank test, of the null hypothesis, H0: median PFS≤7 months vs. H1: median PFS>7 months.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.03
	Comments	Not adjusted for multiple comparisons; One-sided .05 alpha-level test
	Method	Log Rank
	Comments	One-sided test

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
	Comments	For each arm separately, PFS was compared to the historic PFS of first-line docetaxel using a one-sample one-sided log-rank test, of the null hypothesis, H0: median PFS≤7 months vs. H1: median PFS>7 months.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.20
	Comments	Not adjusted for multiple comparisons; One-sided .05 alpha-level test
	Method	Log Rank
	Comments	One-sided test

2. Secondary Outcome

Title	Feasibility of Treatment: Number of Participants Completed Treatment According to the Protocol for at Least 24 Weeks
Description	Whether or not the patient completed treatment according to the protocol for at least 24 weeks. Patients who progressed within 24 weeks were considered as not completing.
Time Frame	Baseline to 24 weeks follow-up

Outcome Measure Data

Analysis Population Description

Intention to treat population

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Measure Participants	83	86	86
Count of Participants [Participants]	40 48.2%	43 50%	44 51.2%

3. Secondary Outcome

Title	Disease Control: Overall Response of Stable Disease for a Duration of ≥24 Weeks
Description	Overall response of stable disease (or non-CR/non-PD for patients with non-measurable disease) for a duration of ≥24 weeks, or better (i.e., partial or complete response) according to RECIST criteria [Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.]
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

Outcome Measure Data

Analysis Population Description

Intention to treat population

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Measure Participants	83	86	86
Count of Participants [Participants]	54 65.1%	59 68.6%	52 60.5%

4. Secondary Outcome

Title	Best Overall Response
Description	Best response according to RECIST 1.1 criteria [assessed by MRI] recorded from the start of treatment across all time points until end of study treatment. Confirmation of partial or complete response by an additional scan was not requested in this trial.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

Outcome Measure Data

Analysis Population Description

Intention to treat population

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Measure Participants	83	86	86
Complete Response (CR)	5 6%	6 7%	4 4.7%
Partial Response (PR)	34 41%	41 47.7%	35 40.7%
Stable Disease (SD)/Non-CR/Non-PD	39 47%	33 38.4%	31 36%
Progressive Disease (PD)	3 3.6%	5 5.8%	11 12.8%
Not Evaluable (NE)	2 2.4%	1 1.2%	5 5.8%

5. Secondary Outcome

Title	Overall Survival
Description	Time from randomization until death from any cause, or censored at date last known alive
Time Frame	Reported after 18.2 months median follow-up since randomization

Outcome Measure Data

Analysis Population Description

Intention to treat population

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Measure Participants	83	86	86
Median (90% Confidence Interval) [months]	25.8	26.2	25.5

6. Secondary Outcome

Title	Changes in Physical Well-being (Change From Day 1 of Cycle 4 to Day 1 of Cycle 6)
Description	Primary quality of life=physical well being; endpoint based on the GLQ 8. The indicator was in Linear Analogue Self-Assessment (LASA) format ranging 0-100 (0=as bad as it can be, 100=as good as it can be).
Time Frame	Assessed from day 1 of cycle 4 through day 1 of cycle 12

Outcome Measure Data

Analysis Population Description

Patients who started the maintenance phase of treatment (cycle 4)

Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15	B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15	C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².	Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Measure Participants	66	72	61
Mean (95% Confidence Interval) [units on a scale]	-2	1	4

Adverse Events

Time Frame	Assessed every 28-day cycle while on treatment and for 30 days after the end of treatment, up to 18 months
Adverse Event Reporting Description	Targeted AEs and other grade 3 or higher AEs were collected on CRFs, regardless of attribution.
Arm/Group Title	A: Nab-Paclitaxel 150 mg/m2 Days 1,15		B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15		C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
Arm/Group Description	Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².		Arm B: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².		Arm C: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity. nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations) *Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
All Cause Mortality
	A: Nab-Paclitaxel 150 mg/m2 Days 1,15		B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15		C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	A: Nab-Paclitaxel 150 mg/m2 Days 1,15		B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15		C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/83 (61.4%)		43/86 (50%)		57/86 (66.3%)
Blood and lymphatic system disorders
Anemia	5/83 (6%)		2/86 (2.3%)		0/86 (0%)
Febrile Neutropenia	2/83 (2.4%)		2/86 (2.3%)		0/86 (0%)
Cardiac disorders
Pericardial effusion	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Ear and labyrinth disorders
Vertigo	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Eye disorders
Cataract	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Dry eye	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Gastrointestinal disorders
Abdominal pain	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Ascites	1/83 (1.2%)		0/86 (0%)		1/86 (1.2%)
Diarrhea	7/83 (8.4%)		3/86 (3.5%)		2/86 (2.3%)
Ileal obstruction	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Ileus	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Mucositis oral	2/83 (2.4%)		1/86 (1.2%)		0/86 (0%)
Nausea	2/83 (2.4%)		1/86 (1.2%)		1/86 (1.2%)
Pancreatitis	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Periodontal disease	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Stomach pain	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Vomiting	1/83 (1.2%)		1/86 (1.2%)		3/86 (3.5%)
General disorders
Edema limbs	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Fatigue	4/83 (4.8%)		4/86 (4.7%)		9/86 (10.5%)
Fever	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Multi-organ failure	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Pain	3/83 (3.6%)		0/86 (0%)		2/86 (2.3%)
Hepatobiliary disorders
Cholecystitis	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Hepatic failure	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Infections and infestations
Appendicitis	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Bronchial infection	0/83 (0%)		0/86 (0%)		2/86 (2.3%)
Lung infection	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Nail infection	0/83 (0%)		1/86 (1.2%)		1/86 (1.2%)
Paronychia	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Rhinitis infective	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Sepsis	0/83 (0%)		2/86 (2.3%)		1/86 (1.2%)
Skin infection	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Soft tissue infection	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Upper respiratory infection	0/83 (0%)		1/86 (1.2%)		1/86 (1.2%)
Urinary tract infection	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Wound infection	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Injury, poisoning and procedural complications
Fracture	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Hip fracture	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Radiation recall reaction (dermatologic)	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Spinal fracture	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Vascular access complication	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Investigations
Neutrophil count decreased	18/83 (21.7%)		24/86 (27.9%)		21/86 (24.4%)
Platelet count decreased	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Alanine aminotransferase increased	3/83 (3.6%)		0/86 (0%)		1/86 (1.2%)
Alkaline phosphatase increased	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Aspartate aminotransferase increased	3/83 (3.6%)		0/86 (0%)		1/86 (1.2%)
Creatinine increased	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
GGT increased	3/83 (3.6%)		1/86 (1.2%)		2/86 (2.3%)
Weight gain	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
White blood cell decreased	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Metabolism and nutrition disorders
Anorexia	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Hypokalemia	3/83 (3.6%)		0/86 (0%)		0/86 (0%)
Hyponatremia	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Hypophosphatemia	1/83 (1.2%)		0/86 (0%)		1/86 (1.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Back pain	0/83 (0%)		2/86 (2.3%)		1/86 (1.2%)
Bone pain	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Musculoskeletal and connective - Other	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Myalgia	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Osteonecrosis of jaw	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Pain in extremity	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Nervous system disorders
Peripheral Sensory Neuropathy	7/83 (8.4%)		4/86 (4.7%)		5/86 (5.8%)
Nervous system disorders - Other	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Seizure	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Spasticity	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Syncope	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Psychiatric disorders
Anxiety	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Depression	2/83 (2.4%)		0/86 (0%)		1/86 (1.2%)
Renal and urinary disorders
Renal and urinary disorders - Other	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Urinary tract obstruction	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Reproductive system and breast disorders
Reproductive system and breast	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Breast pain	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Pelvic pain	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Dyspnea	1/83 (1.2%)		2/86 (2.3%)		1/86 (1.2%)
Epistaxis	0/83 (0%)		1/86 (1.2%)		1/86 (1.2%)
Laryngeal stenosis	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Pleural effusion	1/83 (1.2%)		0/86 (0%)		0/86 (0%)
Respiratory thoracic mediastinal - Other,10038738	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Skin and subcutaneous tissue disorders
Nail ridging	1/83 (1.2%)		0/86 (0%)		1/86 (1.2%)
Periorbital edema	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Photosensitivity	0/83 (0%)		1/86 (1.2%)		0/86 (0%)
Vascular disorders
Hypertension	1/83 (1.2%)		5/86 (5.8%)		4/86 (4.7%)
Thromboembolic event	3/83 (3.6%)		3/86 (3.5%)		4/86 (4.7%)
Other (Not Including Serious) Adverse Events
	A: Nab-Paclitaxel 150 mg/m2 Days 1,15		B: Nab-Paclitaxel 100 mg/m2 Days 1,8,15		C: Nab-Paclitaxel 75 mg/m2 Days 1,8,15,22
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/83 (94%)		83/86 (96.5%)		80/86 (93%)
Blood and lymphatic system disorders
Anemia	46/83 (55.4%)		55/86 (64%)		55/86 (64%)
Cardiac disorders
Heart Failure	0/83 (0%)		0/86 (0%)		3/86 (3.5%)
Sinus Tachycardia	2/83 (2.4%)		4/86 (4.7%)		3/86 (3.5%)
Gastrointestinal disorders
Nausea	32/83 (38.6%)		31/86 (36%)		40/86 (46.5%)
Vomiting	10/83 (12%)		11/86 (12.8%)		17/86 (19.8%)
Diarrhea	21/83 (25.3%)		28/86 (32.6%)		27/86 (31.4%)
Immune system disorders
Allergic Reaction	8/83 (9.6%)		4/86 (4.7%)		4/86 (4.7%)
Investigations
Neutrophil count decreased	28/83 (33.7%)		35/86 (40.7%)		42/86 (48.8%)
Platelet count decreased	8/83 (9.6%)		8/86 (9.3%)		4/86 (4.7%)
Nervous system disorders
Peripheral Sensory Neuropathy	51/83 (61.4%)		58/86 (67.4%)		55/86 (64%)
Recurrent Laryngeal nerve Palsy	0/83 (0%)		0/86 (0%)		1/86 (1.2%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	2/83 (2.4%)		2/86 (2.3%)		4/86 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.