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Study of Modified FOLFOX6 Plus or Minus Sorafenib in Stage IV Metastatic Colorectal Carcinoma (mCRC) Subjects

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Colorectal Cancer, Metastasis, Stage IV, Liver Metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histological confirmation of adenocarcinoma of the colon or rectum
  • Tumor tissue sample available for KRAS and BRAF assessment
  • Measurable metastatic Stage IV disease including at least one measurable lesion that has not previously been radiated
  • No prior chemotherapy for metastatic CRC
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Life expectancy of at least 12 weeks
  • Adequate bone marrow, liver, and renal function; adequate clotting parameters

Exclusion Criteria:

  • Prior treatment with sorafenib
  • Clinical or radiographic evidence of brain metastasis
  • Major surgery, surgical biopsy, or significant traumatic injury within 28 days of randomization; evidence or history of bleeding diathesis or coagulopathy
  • Red blood cell (RBC), white blood cell (WBC), or platelet transfusions and/or growth factor use within 28 days before randomization
  • Adjuvant therapy for CRC (Stage I, II, or III) completed within 12 months before randomization
  • Serious, non-healing wound, ulcer, or bone fracture; Grade 3 or 4 hemorrhage within 28 days before randomization
  • Use of anticoagulation therapy (low dose anticoagulation therapy to mitigate risk of thrombosis due to placement of a semi-permanent central venous port for administration of chemotherapy is allowed. The use of coumadin and related compounds is excluded.)
  • Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg on repeated measurement) despite optimal medical management
  • Thrombolic, embolic, venous, or arterial events (eg, cerebrovascular accident, including transient ischemic attacks) within 6 months before randomization

  • Active cardiac disease including:

    • Congestive heart failure
    • Unstable angina or myocardial infarction within the 6 months before randomization
    • Cardiac ventricular arrhythmias requiring antiarrhythmic treatment
  • Peripheral neuropathy > Grade 1 (CTCAE)
  • Known HIV infection or chronic hepatitis B or C infection
  • Any active infection >/= Grade 2 (CTCAE)
  • Any medical, psychological, or social condition that may interfere with the subject's participation in the study or evaluation of the study results
  • Use of any investigational drug within 28 days or 5 half-lives of that drug, whichever is longer, before randomization
  • Subjects with metastatic CRC who are currently candidates for surgery with curative intent

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6

Matching placebo + mFOLFOX6

Arm Description

Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)

Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression or death due to any cause, whichever occurred first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.

Secondary Outcome Measures

Overall Survival (OS)
Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from date of randomization to disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Overall Response
Overall response of a subject was defined as the best tumor response (Complete Response (CR) or Partial Response (PR)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.
Duration of Response
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) was first documented or to the date of death, whichever occurred first according to Response Evaluation Criteria in Solid Tumors (RECIST). Subjects still having CR or PR and alive at the time of analysis were censored at their last date of tumor evaluation. CR was defined as disappearance of tumor lesions, PR as a decrease of at least 30% and PD as an increase of at least 20% in the sum of tumor lesions sizes.

Full Information

First Posted
February 2, 2009
Last Updated
November 25, 2014
Sponsor
Bayer
Collaborators
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT00865709
Brief Title
Study of Modified FOLFOX6 Plus or Minus Sorafenib in Stage IV Metastatic Colorectal Carcinoma (mCRC) Subjects
Official Title
Phase 2b, DB, Randomized Study Evaluating Efficacy & Safety of Sorafenib Compared With Placebo When Administered in Combination With Modified FOLFOX6 for the Treatment of Metastatic CRC Subjects Previously Untreated for Stage IV Disease
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
Collaborators
Amgen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To determine if sorafenib when added to chemotherapy will slow disease progression more than chemotherapy alone in patients previously untreated for metastatic colorectal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Colorectal Cancer, Metastasis, Stage IV, Liver Metastasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
198 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6
Arm Type
Experimental
Arm Description
Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
Arm Title
Matching placebo + mFOLFOX6
Arm Type
Placebo Comparator
Arm Description
Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
Intervention Description
Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
Intervention Type
Drug
Intervention Name(s)
Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
Intervention Description
Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression or death due to any cause, whichever occurred first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Time Frame
From randomization of the first subject until 23 months later, assessed every 8 weeks.
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Time Frame
From randomization of the first subject until 33 months later.
Title
Time to Progression (TTP)
Description
Time to progression (TTP) was defined as the time from date of randomization to disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Time Frame
From randomization of the first subject until 23 months later, assessed every 8 weeks.
Title
Overall Response
Description
Overall response of a subject was defined as the best tumor response (Complete Response (CR) or Partial Response (PR)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.
Time Frame
From randomization of the first subject until 23 months later, assessed every 8 weeks.
Title
Duration of Response
Description
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) was first documented or to the date of death, whichever occurred first according to Response Evaluation Criteria in Solid Tumors (RECIST). Subjects still having CR or PR and alive at the time of analysis were censored at their last date of tumor evaluation. CR was defined as disappearance of tumor lesions, PR as a decrease of at least 30% and PD as an increase of at least 20% in the sum of tumor lesions sizes.
Time Frame
From randomization of the first subject until 23 months later, assessed every 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological confirmation of adenocarcinoma of the colon or rectum Tumor tissue sample available for KRAS and BRAF assessment Measurable metastatic Stage IV disease including at least one measurable lesion that has not previously been radiated No prior chemotherapy for metastatic CRC Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 Life expectancy of at least 12 weeks Adequate bone marrow, liver, and renal function; adequate clotting parameters Exclusion Criteria: Prior treatment with sorafenib Clinical or radiographic evidence of brain metastasis Major surgery, surgical biopsy, or significant traumatic injury within 28 days of randomization; evidence or history of bleeding diathesis or coagulopathy Red blood cell (RBC), white blood cell (WBC), or platelet transfusions and/or growth factor use within 28 days before randomization Adjuvant therapy for CRC (Stage I, II, or III) completed within 12 months before randomization Serious, non-healing wound, ulcer, or bone fracture; Grade 3 or 4 hemorrhage within 28 days before randomization Use of anticoagulation therapy (low dose anticoagulation therapy to mitigate risk of thrombosis due to placement of a semi-permanent central venous port for administration of chemotherapy is allowed. The use of coumadin and related compounds is excluded.) Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg on repeated measurement) despite optimal medical management Thrombolic, embolic, venous, or arterial events (eg, cerebrovascular accident, including transient ischemic attacks) within 6 months before randomization Active cardiac disease including: Congestive heart failure Unstable angina or myocardial infarction within the 6 months before randomization Cardiac ventricular arrhythmias requiring antiarrhythmic treatment Peripheral neuropathy > Grade 1 (CTCAE) Known HIV infection or chronic hepatitis B or C infection Any active infection >/= Grade 2 (CTCAE) Any medical, psychological, or social condition that may interfere with the subject's participation in the study or evaluation of the study results Use of any investigational drug within 28 days or 5 half-lives of that drug, whichever is longer, before randomization Subjects with metastatic CRC who are currently candidates for surgery with curative intent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
City
Brockton
State/Province
Massachusetts
ZIP/Postal Code
02301
Country
United States
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Antwerpen
ZIP/Postal Code
2020
Country
Belgium
City
Bruxelles - Brussel
ZIP/Postal Code
1000
Country
Belgium
City
Bruxelles - Brussel
ZIP/Postal Code
1070
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Budapest
ZIP/Postal Code
1032
Country
Hungary
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
City
Budapest
ZIP/Postal Code
1106
Country
Hungary
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
City
Gyor
ZIP/Postal Code
9024
Country
Hungary
City
Kecskemet
ZIP/Postal Code
6000
Country
Hungary
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
City
Castelfranco Veneto
State/Province
Treviso
ZIP/Postal Code
31033
Country
Italy
City
Genova
ZIP/Postal Code
16132
Country
Italy
City
Macerata
ZIP/Postal Code
62100
Country
Italy
City
Palermo
ZIP/Postal Code
90146
Country
Italy
City
Pordenone
ZIP/Postal Code
33170
Country
Italy
City
Torino
ZIP/Postal Code
10153
Country
Italy
City
Udine
ZIP/Postal Code
33100
Country
Italy
City
Verona
ZIP/Postal Code
37134
Country
Italy
City
Bialystok
ZIP/Postal Code
15-027
Country
Poland
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
City
Gdynia
ZIP/Postal Code
81-519
Country
Poland
City
Krakow
ZIP/Postal Code
31-115
Country
Poland
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
City
Olsztyn
ZIP/Postal Code
10-228
Country
Poland
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
City
Warszawa
ZIP/Postal Code
04-141
Country
Poland
City
Wroclaw
ZIP/Postal Code
53-413
Country
Poland
City
Alba Iulia
ZIP/Postal Code
510039
Country
Romania
City
Baia Mare
ZIP/Postal Code
430031
Country
Romania
City
Bucharest
ZIP/Postal Code
022326
Country
Romania
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
City
Cluj-Napoca
ZIP/Postal Code
400015
Country
Romania
City
Craiova-Dolj
ZIP/Postal Code
200535
Country
Romania
City
Iasi
ZIP/Postal Code
700106
Country
Romania
City
Oradea
ZIP/Postal Code
410032
Country
Romania
City
Suceava
ZIP/Postal Code
720237
Country
Romania
City
Timisoara
ZIP/Postal Code
300239
Country
Romania
City
Arkhangelsk
ZIP/Postal Code
163045
Country
Russian Federation
City
Astrakhan
ZIP/Postal Code
414041
Country
Russian Federation
City
Chelyabinsk
ZIP/Postal Code
454087
Country
Russian Federation
City
Ekaterinburg
ZIP/Postal Code
620036
Country
Russian Federation
City
Irkutsk
ZIP/Postal Code
664035
Country
Russian Federation
City
Ivanovo
ZIP/Postal Code
153013
Country
Russian Federation
City
Izhevsk
ZIP/Postal Code
426009
Country
Russian Federation
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
City
Khabarovsk
ZIP/Postal Code
680022
Country
Russian Federation
City
Krasnodar
ZIP/Postal Code
350040
Country
Russian Federation
City
Kursk
ZIP/Postal Code
305035
Country
Russian Federation
City
Magnitogorsk
ZIP/Postal Code
455001
Country
Russian Federation
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
City
Moscow
ZIP/Postal Code
121356
Country
Russian Federation
City
Moscow
ZIP/Postal Code
129128
Country
Russian Federation
City
Nizhny Novgorod
ZIP/Postal Code
603001
Country
Russian Federation
City
Novosibirsk
ZIP/Postal Code
630047
Country
Russian Federation
City
Obninsk
ZIP/Postal Code
249036
Country
Russian Federation
City
Pjatygorsk
ZIP/Postal Code
357502
Country
Russian Federation
City
Rostov-on-Don
ZIP/Postal Code
350086
Country
Russian Federation
City
Samara
ZIP/Postal Code
443031
Country
Russian Federation
City
Sochi
ZIP/Postal Code
354057
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
191104
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
194291
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
197110
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
198255
Country
Russian Federation
City
Syktyvkar
ZIP/Postal Code
167904
Country
Russian Federation
City
Tula
ZIP/Postal Code
300053
Country
Russian Federation
City
Ulyanovsk
ZIP/Postal Code
432063
Country
Russian Federation
City
Vladimir
ZIP/Postal Code
600020
Country
Russian Federation
City
Volgograd
ZIP/Postal Code
400138
Country
Russian Federation
City
Yaroslavl
ZIP/Postal Code
150054
Country
Russian Federation
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
City
Manresa
State/Province
Barcelona
ZIP/Postal Code
08240
Country
Spain
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
City
Palma de Mallorca
State/Province
Illes Baleares
ZIP/Postal Code
07010
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Málaga
ZIP/Postal Code
29010
Country
Spain
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Valencia
ZIP/Postal Code
46009
Country
Spain
City
Valencia
ZIP/Postal Code
46010
Country
Spain
City
Cherkassy
ZIP/Postal Code
18009
Country
Ukraine
City
Dnepropetrovsk
ZIP/Postal Code
49102
Country
Ukraine
City
Dnipropetrovsk
ZIP/Postal Code
49055
Country
Ukraine
City
Donetsk
ZIP/Postal Code
83092
Country
Ukraine
City
Ivano-Frankovsk
ZIP/Postal Code
76000
Country
Ukraine
City
Kharkov
ZIP/Postal Code
61070
Country
Ukraine
City
Kiev
ZIP/Postal Code
03022
Country
Ukraine
City
Krivoy Rog
ZIP/Postal Code
50048
Country
Ukraine
City
Lugansk
ZIP/Postal Code
91047
Country
Ukraine
City
Lviv
ZIP/Postal Code
79031
Country
Ukraine
City
Mariupol
ZIP/Postal Code
87500
Country
Ukraine
City
Sumy
ZIP/Postal Code
40005
Country
Ukraine
City
Uzhgorod
ZIP/Postal Code
88014
Country
Ukraine
City
Bristol
State/Province
Avon
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
City
Liverpool
State/Province
Merseyside
ZIP/Postal Code
L7 8XP
Country
United Kingdom
City
Northwood
State/Province
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
City
Belfast
ZIP/Postal Code
BT7 1NN
Country
United Kingdom
City
Glasgow
ZIP/Postal Code
G61 1BD
Country
United Kingdom
City
Hull
ZIP/Postal Code
HU8 9HE
Country
United Kingdom
City
London
ZIP/Postal Code
WC1E 6BT
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
City
Portsmouth
ZIP/Postal Code
PO6 3LY
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23532888
Citation
Tabernero J, Garcia-Carbonero R, Cassidy J, Sobrero A, Van Cutsem E, Kohne CH, Tejpar S, Gladkov O, Davidenko I, Salazar R, Vladimirova L, Cheporov S, Burdaeva O, Rivera F, Samuel L, Bulavina I, Potter V, Chang YL, Lokker NA, O'Dwyer PJ. Sorafenib in combination with oxaliplatin, leucovorin, and fluorouracil (modified FOLFOX6) as first-line treatment of metastatic colorectal cancer: the RESPECT trial. Clin Cancer Res. 2013 May 1;19(9):2541-50. doi: 10.1158/1078-0432.CCR-13-0107. Epub 2013 Mar 26.
Results Reference
result
Links:
URL
http://www.clinicaltrialsregister.eu
Description
Click here and search for Bayer Product information provided by the EMA

Learn more about this trial

Study of Modified FOLFOX6 Plus or Minus Sorafenib in Stage IV Metastatic Colorectal Carcinoma (mCRC) Subjects

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