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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01652482




Registration number
NCT01652482
Ethics application status
Date submitted
26/07/2012
Date registered
30/07/2012
Date last updated
2/11/2016

Titles & IDs
Public title
Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)
Scientific 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
Secondary ID [1] 0 0
2011-005547-27
Secondary ID [2] 0 0
GO28074
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-fluorouracil
Treatment: Drugs - Cetuximab
Treatment: Drugs - Irinotecan
Treatment: Drugs - Leucovorin
Treatment: Drugs - MEHD7945A

Active Comparator: FOLFIRI + Cetuximab -

Experimental: FOLFIRI + MEHD7945A -


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: MEHD7945A
MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria
Timepoint [1] 0 0
approximately 2 year
Secondary outcome [1] 0 0
Plasma Concentration of 5-Fluorouracil
Timepoint [1] 0 0
Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
Secondary outcome [2] 0 0
Plasma Concentration of Irinotecan
Timepoint [2] 0 0
Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
Secondary outcome [3] 0 0
Number of Participants With Anti-MEHD7945A Antibodies
Timepoint [3] 0 0
Pre-dose on Day 1 Cycles 1, 4, and 8; treatment completion visit (up to approximately 2 years)
Secondary outcome [4] 0 0
Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria
Timepoint [4] 0 0
approximately 2 year
Secondary outcome [5] 0 0
Duration of Objective Response According to Modified RECIST v1.1 Criteria
Timepoint [5] 0 0
approximately 2 year
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
approximately 2 year
Secondary outcome [7] 0 0
Number of Participants With Adverse Events
Timepoint [7] 0 0
approximately 2 year
Secondary outcome [8] 0 0
Maximum Observed Serum Concentration (Cmax) of MEHD7945A
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Minimum Observed Serum Concentration (Cmin) of MEHD7945A
Timepoint [9] 0 0
Pre-dose on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2014
Sample size
Target
Accrual to date
Final
135
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- New Lambton Heights
Recruitment hospital [3] 0 0
- St. Leonards
Recruitment hospital [4] 0 0
- Sydney
Recruitment hospital [5] 0 0
- Waratah
Recruitment hospital [6] 0 0
- Wollongong
Recruitment hospital [7] 0 0
- Herston
Recruitment hospital [8] 0 0
- Southport
Recruitment hospital [9] 0 0
- Adelaide
Recruitment hospital [10] 0 0
- Frankston
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
2065 - St. Leonards
Recruitment postcode(s) [4] 0 0
2217 - Sydney
Recruitment postcode(s) [5] 0 0
2298 - Waratah
Recruitment postcode(s) [6] 0 0
2500 - Wollongong
Recruitment postcode(s) [7] 0 0
4029 - Herston
Recruitment postcode(s) [8] 0 0
4215 - Southport
Recruitment postcode(s) [9] 0 0
5041 - Adelaide
Recruitment postcode(s) [10] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles
Country [14] 0 0
Belgium
State/province [14] 0 0
Charleroi
Country [15] 0 0
Belgium
State/province [15] 0 0
Haine-Saint-Paul
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Belgium
State/province [17] 0 0
Liège
Country [18] 0 0
France
State/province [18] 0 0
Creteil
Country [19] 0 0
France
State/province [19] 0 0
Lyon
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Villejuif
Country [22] 0 0
Germany
State/province [22] 0 0
Dresden
Country [23] 0 0
Germany
State/province [23] 0 0
München
Country [24] 0 0
Germany
State/province [24] 0 0
Stuttgart
Country [25] 0 0
Germany
State/province [25] 0 0
Trier
Country [26] 0 0
Italy
State/province [26] 0 0
Lombardia
Country [27] 0 0
Italy
State/province [27] 0 0
Piemonte
Country [28] 0 0
Italy
State/province [28] 0 0
Toscana
Country [29] 0 0
Italy
State/province [29] 0 0
Veneto
Country [30] 0 0
New Zealand
State/province [30] 0 0
Auckland
Country [31] 0 0
New Zealand
State/province [31] 0 0
Christchurch
Country [32] 0 0
New Zealand
State/province [32] 0 0
Dunedin
Country [33] 0 0
New Zealand
State/province [33] 0 0
Tauranga
Country [34] 0 0
Romania
State/province [34] 0 0
Brasov
Country [35] 0 0
Romania
State/province [35] 0 0
Bucharest
Country [36] 0 0
Romania
State/province [36] 0 0
Bucuresti
Country [37] 0 0
Romania
State/province [37] 0 0
Iasi
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Aberdeen
Country [42] 0 0
United Kingdom
State/province [42] 0 0
London
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Oxford
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01652482
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries