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

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ClinicalTrials.gov Identifier: NCT00865709
Recruitment Status : Completed
First Posted : March 19, 2009
Results First Posted : March 20, 2012
Last Update Posted : December 11, 2014
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Bayer

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin) Drug: Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin) Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 198 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : March 2009
Actual Primary Completion Date : January 2011
Actual Study Completion Date : February 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: 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)
Drug: 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)
Placebo Comparator: 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
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



Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks. ]
    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 :
  1. Overall Survival (OS) [ Time Frame: From randomization of the first subject until 33 months later. ]
    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.

  2. Time to Progression (TTP) [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks. ]
    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.

  3. Overall Response [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks. ]
    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.

  4. Duration of Response [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00865709


  Hide Study Locations
Locations
United States, Kansas
Wichita, Kansas, United States, 67214
United States, Louisiana
Metairie, Louisiana, United States, 70006
United States, Massachusetts
Brockton, Massachusetts, United States, 02301
Burlington, Massachusetts, United States, 01805
United States, Texas
Dallas, Texas, United States, 75246
Belgium
Antwerpen, Belgium, 2020
Bruxelles - Brussel, Belgium, 1000
Bruxelles - Brussel, Belgium, 1070
Gent, Belgium, 9000
Leuven, Belgium, 3000
Liege, Belgium, 4000
Hungary
Budapest, Hungary, 1032
Budapest, Hungary, 1097
Budapest, Hungary, 1106
Debrecen, Hungary, 4032
Gyor, Hungary, 9024
Kecskemet, Hungary, 6000
Szeged, Hungary, 6720
Szekesfehervar, Hungary, 8000
Italy
Castelfranco Veneto, Treviso, Italy, 31033
Genova, Italy, 16132
Macerata, Italy, 62100
Palermo, Italy, 90146
Pordenone, Italy, 33170
Torino, Italy, 10153
Udine, Italy, 33100
Verona, Italy, 37134
Poland
Bialystok, Poland, 15-027
Elblag, Poland, 82-300
Gdansk, Poland, 80-952
Gdynia, Poland, 81-519
Krakow, Poland, 31-115
Krakow, Poland, 31-501
Olsztyn, Poland, 10-228
Warszawa, Poland, 02-781
Warszawa, Poland, 04-141
Wroclaw, Poland, 53-413
Romania
Alba Iulia, Romania, 510039
Baia Mare, Romania, 430031
Bucharest, Romania, 022326
Bucharest, Romania, 022328
Cluj-Napoca, Romania, 400015
Craiova-Dolj, Romania, 200535
Iasi, Romania, 700106
Oradea, Romania, 410032
Suceava, Romania, 720237
Timisoara, Romania, 300239
Russian Federation
Arkhangelsk, Russian Federation, 163045
Astrakhan, Russian Federation, 414041
Chelyabinsk, Russian Federation, 454087
Ekaterinburg, Russian Federation, 620036
Irkutsk, Russian Federation, 664035
Ivanovo, Russian Federation, 153013
Izhevsk, Russian Federation, 426009
Kazan, Russian Federation, 420029
Khabarovsk, Russian Federation, 680022
Krasnodar, Russian Federation, 350040
Kursk, Russian Federation, 305035
Magnitogorsk, Russian Federation, 455001
Moscow, Russian Federation, 115478
Moscow, Russian Federation, 121356
Moscow, Russian Federation, 129128
Nizhny Novgorod, Russian Federation, 603001
Novosibirsk, Russian Federation, 630047
Obninsk, Russian Federation, 249036
Pjatygorsk, Russian Federation, 357502
Rostov-on-Don, Russian Federation, 350086
Samara, Russian Federation, 443031
Sochi, Russian Federation, 354057
St. Petersburg, Russian Federation, 191104
St. Petersburg, Russian Federation, 194291
St. Petersburg, Russian Federation, 197022
St. Petersburg, Russian Federation, 197110
St. Petersburg, Russian Federation, 198255
Syktyvkar, Russian Federation, 167904
Tula, Russian Federation, 300053
Ulyanovsk, Russian Federation, 432063
Vladimir, Russian Federation, 600020
Volgograd, Russian Federation, 400138
Yaroslavl, Russian Federation, 150054
Spain
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Manresa, Barcelona, Spain, 08240
Santander, Cantabria, Spain, 39008
Palma de Mallorca, Illes Baleares, Spain, 07010
Barcelona, Spain, 08035
Barcelona, Spain, 08036
Madrid, Spain, 28041
Málaga, Spain, 29010
Sevilla, Spain, 41013
Valencia, Spain, 46009
Valencia, Spain, 46010
Ukraine
Cherkassy, Ukraine, 18009
Dnepropetrovsk, Ukraine, 49102
Dnipropetrovsk, Ukraine, 49055
Donetsk, Ukraine, 83092
Ivano-Frankovsk, Ukraine, 76000
Kharkov, Ukraine, 61070
Kiev, Ukraine, 03022
Krivoy Rog, Ukraine, 50048
Lugansk, Ukraine, 91047
Lviv, Ukraine, 79031
Mariupol, Ukraine, 87500
Sumy, Ukraine, 40005
Uzhgorod, Ukraine, 88014
United Kingdom
Bristol, Avon, United Kingdom, BS2 8ED
Liverpool, Merseyside, United Kingdom, L7 8XP
Northwood, Middlesex, United Kingdom, HA6 2RN
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
Aberdeen, United Kingdom, AB25 2ZN
Belfast, United Kingdom, BT7 1NN
Glasgow, United Kingdom, G61 1BD
Hull, United Kingdom, HU8 9HE
London, United Kingdom, WC1E 6BT
Manchester, United Kingdom, M20 4BX
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Portsmouth, United Kingdom, PO6 3LY
Sponsors and Collaborators
Bayer
Amgen
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Publications of Results:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00865709     History of Changes
Other Study ID Numbers: 13162
2008-005025-11 ( EudraCT Number )
First Posted: March 19, 2009    Key Record Dates
Results First Posted: March 20, 2012
Last Update Posted: December 11, 2014
Last Verified: November 2014

Keywords provided by Bayer:
Colorectal Cancer
Metastasis
Stage IV
Liver Metastasis

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Sorafenib
Fluorouracil
Niacinamide
Leucovorin
Levoleucovorin
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors