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

NCT ID: NCT00865709

Last Updated: 2014-12-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2012-02-29

Brief Summary

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

Detailed Description

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Conditions

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Metastatic Colorectal Cancer

Keywords

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Colorectal Cancer Metastasis Stage IV Liver Metastasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6

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)

Group Type EXPERIMENTAL

Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)

Intervention Type DRUG

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)

Matching placebo + mFOLFOX6

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

Group Type PLACEBO_COMPARATOR

Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)

Intervention Type DRUG

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

Interventions

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Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)

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

Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)

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

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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Wichita, Kansas, United States

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Metairie, Louisiana, United States

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Brockton, Massachusetts, United States

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Burlington, Massachusetts, United States

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Dallas, Texas, United States

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Antwerp, , Belgium

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Bruxelles - Brussel, , Belgium

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Bruxelles - Brussel, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Kecskemét, , Hungary

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Szeged, , Hungary

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Székesfehérvár, , Hungary

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Castelfranco Veneto, Treviso, Italy

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Genova, , Italy

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Macerata, , Italy

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Palermo, , Italy

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Pordenone, , Italy

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Torino, , Italy

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Udine, , Italy

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Verona, , Italy

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Bialystok, , Poland

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Elblag, , Poland

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Gdansk, , Poland

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Gdynia, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Olsztyn, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Alba Iulia, , Romania

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Baia Mare, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Craiova-Dolj, , Romania

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Iași, , Romania

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Oradea, , Romania

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Suceava, , Romania

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Timișoara, , Romania

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Arkhangelsk, , Russia

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Astrakhan, , Russia

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Chelyabinsk, , Russia

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Irkutsk, , Russia

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Ivanovo, , Russia

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Izhevsk, , Russia

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Kazan', , Russia

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Khabarovsk, , Russia

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Krasnodar, , Russia

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Kursk, , Russia

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Magnitogorsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Obninsk, , Russia

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Pjatygorsk, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Sochi, , Russia

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Syktyvkar, , Russia

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Tula, , Russia

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Ulyanovsk, , Russia

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Vladimir, , Russia

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Volgograd, , Russia

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Yaroslavl, , Russia

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Yekaterinburg, , Russia

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Barcelona, Barcelona, Spain

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Barcelona, Barcelona, Spain

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L'Hospitalet de Llobregat, Barcelona, Spain

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Manresa, Barcelona, Spain

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Santander, Cantabria, Spain

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Palma de Mallorca, Illes Baleares, Spain

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Málaga, Málaga, Spain

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Seville, Sevilla, Spain

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Valencia, Valencia, Spain

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Valencia, Valencia, Spain

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Madrid, , Spain

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Cherkassy, , Ukraine

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Dnipro, , Ukraine

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Dnipropetrovsk, , Ukraine

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Donetsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kiev, , Ukraine

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Kryvyi Rih, , Ukraine

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Luhansk, , Ukraine

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Lviv, , Ukraine

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Mariupol, , Ukraine

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Sumy, , Ukraine

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Uzhhorod, , Ukraine

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Bristol, Avon, United Kingdom

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Manchester, Manchester, United Kingdom

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Liverpool, Merseyside, United Kingdom

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Northwood, Middlesex, United Kingdom

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Nottingham, Nottinghamshire, United Kingdom

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Aberdeen, , United Kingdom

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Belfast, , United Kingdom

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Glasgow, , United Kingdom

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Hull, , United Kingdom

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London, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Portsmouth, , United Kingdom

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Countries

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United States Belgium Hungary Italy Poland Romania Russia Spain Ukraine United Kingdom

References

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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.

Reference Type RESULT
PMID: 23532888 (View on PubMed)

Related Links

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http://www.clinicaltrialsregister.eu

Click here and search for Bayer Product information provided by the EMA

Other Identifiers

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2008-005025-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13162

Identifier Type: -

Identifier Source: org_study_id