Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01652482

Collaborator

(none)

135

Enrollment

Locations

Arms

Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label, randomized, multicenter, Phase 2 study will evaluate the safety and efficacy of MEHD7945A when combined with FOLFIRI (folinic acid [leucovorin], 5-fluorouracil [5-FU], and irinotecan) chemotherapy as compared to cetuximab plus FOLFIRI in participants with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type mCRC who have progressed after first-line oxaliplatin-containing chemotherapy for metastatic disease. Participants will be randomized to receive FOLFIRI chemotherapy plus either MEHD7945A or cetuximab. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: 5-fluorouracil Drug: Cetuximab Drug: Irinotecan Drug: Leucovorin Drug: MEHD7945A	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

135 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Multicenter, Open-Label, Randomized Study Evaluating the Efficacy and Safety of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI in Second Line in Patients With KRAS Wildtype Metastatic Colorectal Cancer

Study Start Date :

Oct 1, 2012

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FOLFIRI + Cetuximab	Drug: 5-fluorouracil Standard 5-fluorouracil (5-FU) chemotherapy (400 milligram per square meter [mg/m^2] administered as intravenous bolus and then 5-FU 2400 mg/m^2 administered as continuous intravenous infusion over 46 +/- 2 hours) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity. Other Names: ADRUCIL Drug: Cetuximab Cetuximab 400 mg/m^2 intravenous infusion as a loading dose on Day 1 Cycle 1, followed by 250 mg/m^2 intravenous infusion weekly until documented disease progression or unacceptable toxicity. Other Names: Erbitux Drug: Irinotecan Standard Irinotecan chemotherapy (180 milligram per square meter [mg/m^2] administered as intravenous infusion over 60 +/- 30 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity. Other Names: CAMPTOSAR Drug: Leucovorin Standard Leucovorin chemotherapy (400 mg/m^2 [racemic form] or 200 mg/m^2 [L-isomer form] administered by intravenous infusion over 120 +/- 10 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity. Other Names: WELLCOVORIN
Experimental: FOLFIRI + MEHD7945A	Drug: 5-fluorouracil Standard 5-fluorouracil (5-FU) chemotherapy (400 milligram per square meter [mg/m^2] administered as intravenous bolus and then 5-FU 2400 mg/m^2 administered as continuous intravenous infusion over 46 +/- 2 hours) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity. Other Names: ADRUCIL Drug: Irinotecan Standard Irinotecan chemotherapy (180 milligram per square meter [mg/m^2] administered as intravenous infusion over 60 +/- 30 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity. Other Names: CAMPTOSAR Drug: Leucovorin Standard Leucovorin chemotherapy (400 mg/m^2 [racemic form] or 200 mg/m^2 [L-isomer form] administered by intravenous infusion over 120 +/- 10 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity. Other Names: WELLCOVORIN Drug: MEHD7945A MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.

Arm

Intervention/Treatment

Active Comparator: FOLFIRI + Cetuximab

Drug: 5-fluorouracil

Standard 5-fluorouracil (5-FU) chemotherapy (400 milligram per square meter [mg/m^2] administered as intravenous bolus and then 5-FU 2400 mg/m^2 administered as continuous intravenous infusion over 46 +/- 2 hours) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.

Other Names:

ADRUCIL

Drug: Cetuximab

Cetuximab 400 mg/m^2 intravenous infusion as a loading dose on Day 1 Cycle 1, followed by 250 mg/m^2 intravenous infusion weekly until documented disease progression or unacceptable toxicity.

Other Names:

Erbitux

Drug: Irinotecan

Standard Irinotecan chemotherapy (180 milligram per square meter [mg/m^2] administered as intravenous infusion over 60 +/- 30 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.

Other Names:

CAMPTOSAR

Drug: Leucovorin

Standard Leucovorin chemotherapy (400 mg/m^2 [racemic form] or 200 mg/m^2 [L-isomer form] administered by intravenous infusion over 120 +/- 10 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.

Other Names:

WELLCOVORIN

Experimental: FOLFIRI + MEHD7945A

Drug: 5-fluorouracil

Other Names:

ADRUCIL

Drug: Irinotecan

Other Names:

CAMPTOSAR

Drug: Leucovorin

Other Names:

WELLCOVORIN

Drug: MEHD7945A

MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria [approximately 2 year]

Secondary Outcome Measures

Plasma Concentration of 5-Fluorouracil [Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4]
Plasma Concentration of Irinotecan [Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4]
Number of Participants With Anti-MEHD7945A Antibodies [Pre-dose on Day 1 Cycles 1, 4, and 8; treatment completion visit (up to approximately 2 years)]
Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria [approximately 2 year]
Duration of Objective Response According to Modified RECIST v1.1 Criteria [approximately 2 year]
Overall Survival (OS) [approximately 2 year]
Number of Participants With Adverse Events [approximately 2 year]
Maximum Observed Serum Concentration (Cmax) of MEHD7945A [Pre-dose and 30 minutes after end of infusion on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)]
Minimum Observed Serum Concentration (Cmin) of MEHD7945A [Pre-dose on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum, with KRAS wild-type status
Progressive disease on or after first-line oxaliplatin-containing regimen for mCRC; participants must have received oxaliplatin-containing chemotherapy for greater than or equal to (>/=) 3 months; no more than one prior chemotherapy regimen for metastatic disease is allowed
Measurable disease per modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate hematologic and end-organ function

Exclusion Criteria:

Prior treatment with irinotecan
Prior treatment with an investigational or approved human epidermal growth factor receptor (HER)-targeted agent
Last anti-tumor therapy within 4 weeks prior to Cycle 1, Day 1
Leptomeningeal disease as the only manifestation of the current malignancy
Active infection requiring intravenous antibiotics
Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs
Current severe, uncontrolled systemic disease
Known human immunodeficiency virus (HIV) infection
Untreated/active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
Pregnant or lactating women
Malignancies other than colorectal cancer within 5 years prior to randomization, except for adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Bakersfield	California	United States	93309
2	Fullerton	California	United States	92835
3	Los Angeles	California	United States	90033
4	Los Angeles	California	United States	90095
5	San Luis Obispo	California	United States	93454
6	Santa Barbara	California	United States	93105
7	Aurora	Colorado	United States	80045
8	Orange Park	Florida	United States	32073
9	Harvey	Illinois	United States	60426
10	Paducah	Kentucky	United States	42003
11	Rockville	Maryland	United States	20850
12	Boston	Massachusetts	United States	02114
13	Boston	Massachusetts	United States	02215
14	Detroit	Michigan	United States	48201
15	Jefferson City	Missouri	United States	65109
16	Las Vegas	Nevada	United States	89148
17	Philadelphia	Pennsylvania	United States	19104
18	Kirkland	Washington	United States	98034
19	Seattle	Washington	United States	98109
20	Darlinghurst	New South Wales	Australia	2010
21	New Lambton Heights	New South Wales	Australia	2305
22	St. Leonards	New South Wales	Australia	2065
23	Sydney	New South Wales	Australia	2217
24	Waratah	New South Wales	Australia	2298
25	Wollongong	New South Wales	Australia	2500
26	Herston	Queensland	Australia	4029
27	Southport	Queensland	Australia	4215
28	Adelaide	South Australia	Australia	5041
29	Frankston	Victoria	Australia	3199
30	Bruxelles		Belgium	1200
31	Charleroi		Belgium	B6000
32	Haine-Saint-Paul		Belgium	7100
33	Leuven		Belgium	3000
34	Liège		Belgium	4000
35	Creteil		France	94000
36	Lyon		France	69373
37	Paris		France	75015
38	Villejuif		France	94805
39	Dresden		Germany	01307
40	München		Germany	81737
41	München		Germany	81925
42	Stuttgart		Germany	70199
43	Trier		Germany	54290
44	Milano	Lombardia	Italy	20133
45	Milano	Lombardia	Italy	20162
46	Orbassano	Piemonte	Italy	10043
47	Pisa	Toscana	Italy	56100
48	Padova	Veneto	Italy	35128
49	Auckland		New Zealand	1142
50	Christchurch		New Zealand	8011
51	Dunedin		New Zealand	9001
52	Tauranga		New Zealand	3112
53	Brasov		Romania	500091
54	Bucharest		Romania	022328
55	Bucuresti		Romania	030171
56	Iasi		Romania	700106
57	Barcelona		Spain	08035
58	Barcelona		Spain	08036
59	Madrid		Spain	28007
60	Madrid		Spain	28050
61	Valencia		Spain	46010
62	Aberdeen		United Kingdom	AB25 2ZN
63	London		United Kingdom	NW1 2BU
64	Oxford		United Kingdom	OX3 7LJ
65	Wirral		United Kingdom	CH63 4JY