Clinical trial NCT00865709: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Colorectal Cancer
Metastasis
Stage IV
Liver Metastasis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2009-03-19
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization of the first subject until 23 months later, assessed every 8 weeks.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization of the first subject until 33 months later.
measure: Time to Progression (TTP)
timeFrame: From randomization of the first subject until 23 months later, assessed every 8 weeks.
measure: Overall Response
timeFrame: From randomization of the first subject until 23 months later, assessed every 8 weeks.
measure: Duration of Response
timeFrame: From randomization of the first subject until 23 months later, assessed every 8 weeks
Other outcomes:
Locations:
city: Wichita
country: United States
state: Kansas
city: Metairie
country: United States
state: Louisiana
city: Brockton
country: United States
state: Massachusetts
city: Burlington
country: United States
state: Massachusetts
city: Dallas
country: United States
state: Texas
city: Antwerpen
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Gyor
country: Hungary
city: Kecskemet
country: Hungary
city: Szeged
country: Hungary
city: Szekesfehervar
country: Hungary
city: Castelfranco Veneto
country: Italy
state: Treviso
city: Genova
country: Italy
city: Macerata
country: Italy
city: Palermo
country: Italy
city: Pordenone
country: Italy
city: Torino
country: Italy
city: Udine
country: Italy
city: Verona
country: Italy
city: Bialystok
country: Poland
city: Elblag
country: Poland
city: Gdansk
country: Poland
city: Gdynia
country: Poland
city: Krakow
country: Poland
city: Krakow
country: Poland
city: Olsztyn
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Alba Iulia
country: Romania
city: Baia Mare
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Craiova-Dolj
country: Romania
city: Iasi
country: Romania
city: Oradea
country: Romania
city: Suceava
country: Romania
city: Timisoara
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Astrakhan
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Irkutsk
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Izhevsk
country: Russian Federation
city: Kazan
country: Russian Federation
city: Khabarovsk
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Kursk
country: Russian Federation
city: Magnitogorsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Obninsk
country: Russian Federation
city: Pjatygorsk
country: Russian Federation
city: Rostov-on-Don
country: Russian Federation
city: Samara
country: Russian Federation
city: Sochi
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Syktyvkar
country: Russian Federation
city: Tula
country: Russian Federation
city: Ulyanovsk
country: Russian Federation
city: Vladimir
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Manresa
country: Spain
state: Barcelona
city: Santander
country: Spain
state: Cantabria
city: Palma de Mallorca
country: Spain
state: Illes Baleares
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Cherkassy
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano-Frankovsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Krivoy Rog
country: Ukraine
city: Lugansk
country: Ukraine
city: Lviv
country: Ukraine
city: Mariupol
country: Ukraine
city: Sumy
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Bristol
country: United Kingdom
state: Avon
city: Liverpool
country: United Kingdom
state: Merseyside
city: Northwood
country: United Kingdom
state: Middlesex
city: Nottingham
country: United Kingdom
state: Nottinghamshire
city: Aberdeen
country: United Kingdom
city: Belfast
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Hull
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Portsmouth
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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.