A Study of Onartuzumab (MetMAb) in Combination With mFOLFOX6 in Patients With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2) Negative Gastroesophageal Cancer

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01590719

Collaborator

Genentech, Inc. (Industry)

123

Enrollment

Locations

Arms

Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with mFOLFOX6 in patients with metastatic HER2-negative adenocarcinoma of the stomach or gastroesophageal junction. Patients will be randomized in a 1:1 ratio to receive either onartuzumab (MetMAb) or placebo in combination with mFOLFOX6. Patients may continue to receive onartuzumab (MetMAb) or placebo until disease progression, unacceptable toxicity, patient or physician decision to discontinue treatment.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: Placebo Drug: Onartuzumab (MetMAb) Drug: Oxaliplatin Drug: Folinic acid Drug: Levofolinic acid Drug: 5-Fluorouracil	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

123 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 Efficacy And Safety Of Onartuzumab (MetMAb) In Combination With 5-Fluorouracil, Folinic Acid, And Oxaliplatin (mFOLFOX6) In Patients With Metastatic HER2-Negative Gastroesophageal Cancer

Study Start Date :

Jul 1, 2012

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Onartuzumab (MetMAb) with mFOLFOX6 Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin)	Drug: Onartuzumab (MetMAb) Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: Oxaliplatin Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: Folinic acid Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: Levofolinic acid If folinic acid is unavailable: levofolinic acid 200 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: 5-Fluorouracil 5-Fluorouracil 400 mg/m2 IV followed by 2400 mg/m2 IV infusion every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment
Placebo Comparator: Placebo with mFOLFOX6 Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin)	Drug: Placebo Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: Oxaliplatin Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: Folinic acid Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: Levofolinic acid If folinic acid is unavailable: levofolinic acid 200 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment Drug: 5-Fluorouracil 5-Fluorouracil 400 mg/m2 IV followed by 2400 mg/m2 IV infusion every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Arm

Intervention/Treatment

Experimental: Onartuzumab (MetMAb) with mFOLFOX6

Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin)

Drug: Onartuzumab (MetMAb)

Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: Oxaliplatin

Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: Folinic acid

Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: Levofolinic acid

If folinic acid is unavailable: levofolinic acid 200 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: 5-Fluorouracil

5-Fluorouracil 400 mg/m2 IV followed by 2400 mg/m2 IV infusion every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Placebo Comparator: Placebo with mFOLFOX6

Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin)

Drug: Placebo

Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: Oxaliplatin

Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: Folinic acid

Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: Levofolinic acid

If folinic acid is unavailable: levofolinic acid 200 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Drug: 5-Fluorouracil

5-Fluorouracil 400 mg/m2 IV followed by 2400 mg/m2 IV infusion every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) in all patients [Up to 18 months]
Progression-free survival (PFS) in patients with Met-positive tumors [Up to 18 months]

Secondary Outcome Measures

Safety: incidence of adverse events [18 months]
Overall survival (OS) [18 months]
Overall response rate (ORR) [18 months]
Duration of response (DOR) [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients, 18 years of age and older
Adenocarcinoma of the stomach or gastroesophageal junction with inoperable, metastatic disease, not amenable for curative therapy
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Life expectancy >3 months
Presence of tissue sample for immunohistochemistry assay of Met receptor and HER2 status (if unknown)
Radiographic evidence of disease; measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1); Patients with peritoneal disease would generally be regarded as having evaluable disease and allowed to enter the trial.
For women who are not postmenopausal or surgically sterile; agreement to use an adequate method of contraception (e.g., hormonal implant) during the treatment period and for at least 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin
For men: agreement to use a barrier method of contraception during the treatment period and for 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin
Adequate laboratory values

Exclusion Criteria:

HER2-positive tumor (primary tumor or metastasis)
Previous chemotherapy for locally advanced or metastatic gastric carcinoma (adjuvant or neoadjuvant chemotherapy must be completed at least 6 months prior to randomization)
Prior treatment with investigational drugs that target the hepatocyte growth factor (HGF) or Met pathway
History of other malignancy within the previous 5 years, except for appropriately treated and presumed cured carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, and localized prostate cancer
Receipt of an investigational drug within 28 days prior to study start
Clinically significant gastrointestinal abnormalities, except from gastric cancer (e.g., Crohn's disease)
Significant history of cardiac disease
Significant vascular disease
Infection with human immunodeficiency virus, hepatitis B, or hepatitis C

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Denver	Colorado	United States	80218
2	New Haven	Connecticut	United States	06520
3	Fort Myers	Florida	United States	33908
4	St Petersburg	Florida	United States	33705
5	Chicago	Illinois	United States	60637
6	Niles	Illinois	United States	60714
7	Albany	New York	United States	12206
8	New York	New York	United States	10065
9	Cincinnati	Ohio	United States	45219
10	Nashville	Tennessee	United States	37203
11	Austin	Texas	United States	78731
12	Bedford	Texas	United States	76022
13	Garland	Texas	United States	77060
14	The Woodlands	Texas	United States	77380
15	Tyler	Texas	United States	75702
16	Fairfax	Virginia	United States	22031
17	Richmond	Virginia	United States	23226
18	Vancouver	Washington	United States	98684
19	Sydney	New South Wales	Australia	2139
20	Herston	Queensland	Australia	4029
21	Woodville South	South Australia	Australia	5011
22	East Bentleigh	Victoria	Australia	VIC 3165
23	Heidelberg	Victoria	Australia	3084
24	Nedlands	Western Australia	Australia	6009
25	Seoul		Korea, Republic of	05505
26	Seoul		Korea, Republic of	06351
27	Seoul		Korea, Republic of	135-720
28	Singapore		Singapore	119228
29	Singapore		Singapore	169610
30	Tainan		Taiwan	00704
31	Taipei		Taiwan	00112
32	Taipei		Taiwan	100
33	Taoyuan County		Taiwan	333
34	Bangkok		Thailand	10330
35	Bangkok		Thailand	10400
36	Bangkok		Thailand	10700