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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00865709
• Other study ID #: 13162
• Secondary ID: 2008-005025-11
• Status: Completed
• Phase: Phase 2
• First received: February 2, 2009
• Last updated: November 25, 2014
• Start date: March 2009
• Est. completion date: February 2012

Study information

• Verified date: November 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPSpain: Agencia espanola de medicamentos y productos sanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyRomania: National Medicine AgencyRussia: Federal Service for Control of Healthcare and Social Development - Roszdravnadzor (Scientific Center for pharmaceuticals expertise)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 198
• Est. completion date: February 2012
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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)
• 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Onyx Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Hungary,  Italy,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

References & Publications (1)

Tabernero J, Garcia-Carbonero R, Cassidy J, Sobrero A, Van Cutsem E, Köhne 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 comb — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From randomization of the first subject until 23 months later, assessed every 8 weeks.	No
Secondary	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.	From randomization of the first subject until 33 months later.	No
Secondary	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.	From randomization of the first subject until 23 months later, assessed every 8 weeks.	No
Secondary	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.	From randomization of the first subject until 23 months later, assessed every 8 weeks.	No
Secondary	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.	From randomization of the first subject until 23 months later, assessed every 8 weeks	No

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