Phase II study comparing sorafenib to placebo when administered in combination with chemotherapy for the treatment of metastatic colorectal cancer in Subjects Who Have Not Been Previously Treated for Stage IV Disease.

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2008-005025-11-GB
• Date of registration: 27/11/2008
• Prospective Registration: Yes
• Primary sponsor: Bayer Healthcare AG, D-51368 Leverkusen, Germany
• Public title: Phase II study comparing sorafenib to placebo when administered in combination with chemotherapy for the treatment of metastatic colorectal cancer in Subjects Who Have Not Been Previously Treated for Stage IV Disease.
• Scientific title: A Phase 2b, Double Blind, Randomized Study Evaluating the Efficacy and Safety of Sorafenib Compared With Placebo When Administered in Combination With Chemotherapy (Modified FOLFOX6) for the Treatment of Metastatic Colorectal Cancer in Subjects Who Have Not Been Previously Treated for Stage IV Disease
• Date of first enrolment: 06/05/2009
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005025-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: mFOLFOX6: oxaliplatin, LLV and 5-FU

Countries of recruitment

Belgium, Romania, Russian Federation, Spain, United Kingdom, United States

Contacts

• Name: Bayer Clin. Trials Contact CTP Team
• Affiliation: Bayer HealthCare AG

• Name: Bayer Clin. Trials Contact CTP Team
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Age > or = 18 years
• Histological confirmation of adenocarcinoma of the colon or rectum
• Tumor tissue sample available for KRAS and BRAF assessments
• Measurable metastatic Stage IV disease (per the American Joint Committee on Cancer [AJCC] Tumor, Node, and Metastasis [TNM] Staging System for CRC) documented within 28 days before randomization)
• No prior chemotherapy for metastatic CRC
• At least 1 measurable metastatic lesion that has not been irradiated. The lesion will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST), and be documented by radiological evaluation within 28 days before randomization
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Life expectancy of at least 12 weeks
• Prior radiation therapy is allowed but must be completed at least 28 days before randomization (if applicable)
• Adequate bone marrow, liver, and renal function as assessed by:
• Hemoglobin > or = 9.0 g/dL (transfusion and growth factor independent)
• Platelet count > or = 100,000/mm3 (transfusion independent)
• Absolute neutrophil count (ANC) > or = 1500/mm3 (growth factor independent)
• Total bilirubin < or = 2.0 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT [SGPT]) and aspartate aminotransferase (AST [SGOT]) < or = 5.0 x ULN in the presence of liver metastasis; ALT (SGPT) and AST (SGOT) < or = 2.5 x ULN in the absence of liver metastasis
• Prothrombin time (PT) or international normalized ratio for PT (PT INR) < or = 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) < or = 1.5 x ULN
• Serum creatinine < or = 1.5 times ULN
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days before randomization. Both men and women participating in this study must use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double barrier method), beginning at the signing of the Informed Consent Form (ICF) and for > or = 30 days after the last study drug administration
• Subject must have the ability, in the opinion of the investigator, to comply with all study procedures and follow-up examinations
• Subjects (and/or legal guardian[s]) must understand and be able and willing to sign an ICF that must be appropriately obtained before undertaking any study specific procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Prior treatment with sorafenib
• Clinical or radiographic evidence of brain metastasis
• Major surgery, open surgical biopsy, or significant traumatic injury within 28 days before randomization; large bore needle biopsy of a major organ within 14 days before randomisation. Placement of central venous access port >= 3 days before randomisation is permitted.
• 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, nonhealing wound, ulcer, or bone fracture
• A Grade 3 or 4 (per Common Terminology Criteria for Adverse Events v3.0 [CTCAE] dictionary) hemorrhage within 28 days before randomization
• Use of anticoagulation therapy for the treatment of thrombotic events (such as deep venous thrombosis or pulmonary embolism) or use of anticoagulation therapy resulting in abnormal coagulation parameters. (Low dose anticoagulation therapy to mitigate risk of thrombosis due to placement of a semipermanent central venous port for administration of chemotherapy is allowed.)
• 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 – New York Heart Association (NYHA) > Class II
• Unstable angina (anginal symptoms at rest), new onset angina (within 3 months), or myocardial infarction within the 6 months before randomization
• Cardiac ventricular arrhythmias requiring antiarrhythmic treatment within 3 months before randomisation
• Current peripheral neuropathy > Grade 1 (CTCAE)
• Subjects with metastatic CRC who are currently candidates for surgery with curative intent (eg, solitary line metastasis)
• Use of phenytoin, carbamazepine, phenobarbital, St. John’s Wort, or rifampin (rifampicin) within 28 days before randomization
• Therapeutic anticoagulation with vitamin K antagonists such as warfarin or with heparins and heparinoids, except for:
• Low-dose warfarin (1mg PO QD) with INR <= 1.5 x ULN is permitted
• Low-dose aspirin is permitted <= 100mg daily
• Prophylactic doses of heparins are permitted
• Current infection > or = Grade 2 (CTCAE)
• Any anticancer treatment (chemotherapy, hormonal treatment, radiation treatment, surgery, immunotherapy, biologic therapy, or tumor embolization) within 28 days before randomization
• Any previous or concurrent cancer. Subjects with successfully treated, noninvasive cancers, including cervical cancer in situ, basal cell carcinoma, or superficial bladder tumors (Ta and Tis) will be allowed to participate in the study. Subjects with cancer that was curatively treated > 5 years before randomization will also be allowed to participate in the study
• Known human immunodeficiency virus infection or chronic hepatitis B or C infection
• Known or suspected allergy or hypersensitivity to any component of sorafenib, 5-FU, LLV or leucovorin, or oxaliplatin
• Any medical, psychological, or social condition that may interfere with the subject’s participation in the study or evaluation of the study results
• Women who are pregnant or breast feeding
• Subject

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

The patient population includes patients with Stage IV metastatic colorectal cancer (mCRC), with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Patients must have measurable disease and must not have received prior systemic anticancer therapy for mCRC.
MedDRA version: 14.1 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: NEXAVAR
Product Name: Sorafenib
Product Code: Bay 43-9006
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sorafenib
CAS Number: 284461-73-0
Current Sponsor code: BAY-43-9006
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is PFS, which will be measured from the date of randomization to the date of first observed progressive disease (PD, radiological or clinical, whichever is earlier) or the date of death due to any cause (if occurring before progression). For subjects without documented progression or death at the time of analysis, the PFS will be censored at the last date of tumor assessment. If a subject has no tumor assessments after Baseline, then the subject will be censored at Day 1.

Main Objective: The objective of this phase 2 study is to evaluate the antitumor activity, safety, and tolerability of sorafenib versus placebo when used in combination with mFOLFOX6 (5-fluorouracil [5-FU], levo-leucovorin [LLV], and oxaliplatin) in subjects with mCRC who have not been previously treated for Stage IV disease.

The primary efficacy objective is to compare progression-free survival (PFS) in subjects receiving sorafenib in combination with mFOLFOX6 versus subjects receiving placebo in combination with mFOLFOX6.

Secondary Objective: The secondary objectives are to compare the treatment groups in terms of:
• Overall survival (OS)
• Time to progression (TTP)
• Overall response rate (ORR)
• Duration of overall response (OR)
• Safety and tolerability

Timepoint(s) of evaluation of this end point: Will be measured from the date of randomization to the date of first observed progressive disease (PD, radiological or clinical, whichever is earlier) or the date of death due to any cause (if occurring before progression)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Overall survival will be measured from the date of randomization to death due to any cause.

Time to progression will be measured from the date of randomization to the date of first observed PD (radiological or clinical, whichever is earlier).


Duration of OR will be measured from the date of the first documentation of PR or CR (whichever status is recorded first) to the first date that PD or death due to any cause is documented.

Secondary end point(s): - Overall survival
- Time to progression
- Overall response rate
- Duration of overall response

Secondary ID(s)

BAY43-9006/13162

Source(s) of Monetary Support

BayerHealthCare AG