Study Evaluating the Safety and Efficacy of Onartuzumab And/or Bevacizumab in Combination With Paclitaxel in Participants With Metastatic, Triple Negative Breast Cancer

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01186991

Collaborator

Hoffmann-La Roche (Industry)

185

Enrollment

Locations

Arms

Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, Phase II, double-blind, multicenter, placebo-controlled trial designed to preliminarily estimate the efficacy and evaluate the safety and tolerability of onartuzumab (MetMAb) + bevacizumab + paclitaxel and onartuzumab + placebo + paclitaxel versus placebo + bevacizumab + paclitaxel in participants with metastatic or locally recurrent, triple-negative breast cancer who either have not received treatment (first-line) or have progressed after one conventional cytotoxic chemotherapy regimen (second-line).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Onartuzumab Drug: Bevacizumab Drug: Paclitaxel Drug: Bevacizumab Placebo Drug: Onartuzumab Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

185 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Onartuzumab And/or Bevacizumab in Combination With Paclitaxel in Patients With Metastatic, Triple-Negative Breast Cancer

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Onartuzumab + Bevacizumab + Paclitaxel Participants will receive treatment with onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable drug-related toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years).	Drug: Onartuzumab Onartuzumab will be administered as intravenous (IV) infusion at a dose of 10 milligrams per kilogram (mg/kg) on Day 1 and Day 15 of each 28-day cycle. The dose of onartuzumab will be based on the participant's weight at screening and will remain the same throughout the study. Other Names: MetMAb Drug: Bevacizumab Bevacizumab will be administered as IV infusion at a dose of 10 mg/kg on Day 1 and Day 15 of each 28-day cycle. The dose of bevacizumab will be based on the participant's weight at screening and will remain the same throughout the study. Other Names: Avastin Drug: Paclitaxel Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle. Other Names: Taxol
Experimental: Onartuzumab + Placebo + Paclitaxel Participants will receive treatment with onartuzumab, placebo matching to bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years).	Drug: Onartuzumab Onartuzumab will be administered as intravenous (IV) infusion at a dose of 10 milligrams per kilogram (mg/kg) on Day 1 and Day 15 of each 28-day cycle. The dose of onartuzumab will be based on the participant's weight at screening and will remain the same throughout the study. Other Names: MetMAb Drug: Paclitaxel Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle. Other Names: Taxol Drug: Bevacizumab Placebo Placebo matching to bevacizumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.
Active Comparator: Placebo + Bevacizumab + Paclitaxel Participants will receive treatment with placebo matching to onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years).	Drug: Bevacizumab Bevacizumab will be administered as IV infusion at a dose of 10 mg/kg on Day 1 and Day 15 of each 28-day cycle. The dose of bevacizumab will be based on the participant's weight at screening and will remain the same throughout the study. Other Names: Avastin Drug: Paclitaxel Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle. Other Names: Taxol Drug: Onartuzumab Placebo Placebo matching to onartuzumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.

Arm

Intervention/Treatment

Experimental: Onartuzumab + Bevacizumab + Paclitaxel

Participants will receive treatment with onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable drug-related toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years).

Drug: Onartuzumab

Onartuzumab will be administered as intravenous (IV) infusion at a dose of 10 milligrams per kilogram (mg/kg) on Day 1 and Day 15 of each 28-day cycle. The dose of onartuzumab will be based on the participant's weight at screening and will remain the same throughout the study.

Other Names:

MetMAb

Drug: Bevacizumab

Bevacizumab will be administered as IV infusion at a dose of 10 mg/kg on Day 1 and Day 15 of each 28-day cycle. The dose of bevacizumab will be based on the participant's weight at screening and will remain the same throughout the study.

Other Names:

Avastin

Drug: Paclitaxel

Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle.

Other Names:

Taxol

Experimental: Onartuzumab + Placebo + Paclitaxel

Participants will receive treatment with onartuzumab, placebo matching to bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years).

Drug: Onartuzumab

Other Names:

MetMAb

Drug: Paclitaxel

Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle.

Other Names:

Taxol

Drug: Bevacizumab Placebo

Placebo matching to bevacizumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.

Active Comparator: Placebo + Bevacizumab + Paclitaxel

Participants will receive treatment with placebo matching to onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years).

Drug: Bevacizumab

Other Names:

Avastin

Drug: Paclitaxel

Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle.

Other Names:

Taxol

Drug: Onartuzumab Placebo

Placebo matching to onartuzumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.

Outcome Measures

Primary Outcome Measures

Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants Who Have not Received Prior Systemic Therapy or Have Progressed to Prior First-line Treatment [From randomization until disease progression (PD), relapse, or death on study (within 30 days of last study drug administration) from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years)]

Secondary Outcome Measures

PFS According to RECIST v1.1 in Participants Who Have not Received Prior Systemic Therapy [From randomization until PD, relapse, or death on study from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years)]
Percentage of Participants With Objective Response as Assessed by the Investigator According to RECIST v1.1 [From randomization until PD, relapse, or death on study from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years)]
Duration of Response as Assessed by the Investigator Using RECIST v1.1 [From initial objective response to PD or death on study from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years)]
Overall Survival (OS) [From randomization until death from any cause, loss to follow-up, study termination by sponsor, or participant's withdrawal in survival follow-up (overall up to 5 years)]
Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs) [Day 1 Cycle 1 (cycle length=28 days) up to 30 days after last dose of study drug or study discontinuation/termination, whichever is later (overall up to 5 years)]
Number of Cycles of Treatment Received for Onartuzumab, Paclitaxel, and Bevacizumab During the Study [Day 1 Cycle 1 (cycle length=28 days) up to last dose of study drug or study discontinuation/termination, whichever is later (overall up to 5 years)]
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab [Predose on Day 1 of Cycles 1-4 (cycle length=28 days), 30 days after last administration of onartuzumab or initiation of another therapy (overall up to 5 years)]
Serum Levels of ATAs Against Onartuzumab [Predose on Day 1 of Cycles 1-4 (cycle length=28 days), 30 days after last administration of onartuzumab or initiation of another therapy (overall up to 5 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor 2 (HER2)-negative (triple-negative) adenocarcinoma of the breast
Confirmed availability of tumor tissue

Exclusion Criteria:

Prior therapy with two or more regimens for metastatic breast cancer
Any systemic anti-cancer therapy within 3 weeks prior to Day 1 of Cycle 1
Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Day 1 of Cycle 1
Prior therapy with a taxane for metastatic breast cancer
Prior therapy with bevacizumab, sorafenib, sunitinib, or other putative vascular endothelial growth factor (VEGF) pathway-targeted therapy following diagnosis of breast cancer
Prior therapy with hormones and/or trastuzumab
Inadequate hematology, renal, or hepatic organ function

Bevacizumab Exclusion Criteria:

Uncontrolled hypertension (systolic pressure greater than [>] 150 millimeters of mercury [mmHg] and/or diastolic pressure > 100 mmHg), with or without anti-hypertensive medication
Evidence of bleeding diathesis or coagulopathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Blood/Cancer Ctr	Bakersfield	California	United States	93309
2	St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr	Fullerton	California	United States	92835
3	Can Care Assoc Med Group Inc; Beach Cities Offices	Los Angeles	California	United States	90095-1772
4	Univ of California Los Angeles	Los Angeles	California	United States	90095
5	Kaiser Permanente Sacramento Medical Center	Sacramento	California	United States	95825
6	Sharp Healthcare; Oncology Research Program	San Diego	California	United States	92123
7	Kaiser Permanente - Vallejo	Vallejo	California	United States	94589
8	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
9	Florida Cancer Specialists; SCRI	Fort Myers	Florida	United States	33916
10	Suburban Hematology Oncology	Lawrenceville	Georgia	United States	30045
11	Cancer Center of Kansas	Wichita	Kansas	United States	67214-3728
12	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
13	Karmanos Cancer Institute..	Detroit	Michigan	United States	48201
14	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89128
15	North Shore Hem Onc Associates	East Setauket	New York	United States	11733
16	Duke University Medical Center	Durham	North Carolina	United States	27710
17	Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
18	Charleston Hematology Oncology	Charleston	South Carolina	United States	29414
19	South Carolina Onc. Associate	Columbia	South Carolina	United States	29210
20	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee	United States	37404
21	The Sarah Cannon Research Inst	Nashville	Tennessee	United States	37203
22	MD Anderson Cancer Center	Houston	Texas	United States	77030
23	Northern Utah Associates	Ogden	Utah	United States	84403
24	Institut Jules Bordet	Bruxelles		Belgium	1000
25	UZ Antwerpen	Edegem		Belgium	2650
26	AZ Sint Lucas (Sint Lucas)	Gent		Belgium	9000
27	CH Jolimont - Lobbes (Jolimont)	Haine-Saint-Paul		Belgium	7100
28	Jessa Zkh (Campus Virga Jesse)	Hasselt		Belgium	3500
29	CHU Sart-Tilman	Liège		Belgium	4000
30	Sint Augustinus Wilrijk	Wilrijk		Belgium	2610
31	Institut Bergonie; Oncologie	Bordeaux		France	33076
32	Centre Francois Baclesse; Gastro-Enterologie	Caen		France	14076
33	Centre Georges Francois Leclerc; Oncologie 3	Dijon		France	21079
34	Centre Leon Berard	Lyon		France	69008
35	Institut régional du Cancer Montpellier	Montpellier		France	34298
36	Institut Curie; Oncologie Medicale	Paris		France	75231
37	Ico Rene Gauducheau; Oncologie	Saint Herblain		France	44805
38	Centre Rene Huguenin; CONSULT SPECIALISEES	St Cloud		France	92210
39	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse		France	31059
40	Praxis Dr. med. Klausmann; SHOD	Aschaffenburg		Germany	63739
41	Klinik Johann Wolfgang von Goethe Uni	Frankfurt am Main		Germany	60590
42	Klinikum rechts der Isar der TU München; Frauenklinik	Muenchen		Germany	81675
43	Universitätsklinik Tübingen; Frauenklinik	Tübingen		Germany	72076
44	Hospital Universitario Puerta del Mar; Servicio de Oncologia	Cádiz	Cadiz	Spain	11009
45	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid	Spain	28222
46	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
47	Instituto Catalán de Oncología; Servicio de Farmacia	Barcelona		Spain	08907
48	Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia	La Coruña		Spain	15009
49	Brighton and Sussex Univ Hosp	Brighton		United Kingdom	BN2 5BD
50	Christie Hospital NHS Trust	Manchester		United Kingdom	M20 4BX
51	Mount Vernon Hospital; Centre For Cancer Treatment	Northwood		United Kingdom	HA6 2RN
52	Nottingham City Hospital; Oncology	Nottingham		United Kingdom	NG5 1PB
53	The Clatterbridge Cancer Ctr For Oncolgy	Wirral		United Kingdom	CH63 4JY