Metastatic adenocarcinoma of the colon or rectum (metastatic CRC) MedDRA version: 16.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Sponsors
Bayer Health Care AG, D-51368 Leverkusen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male or female subjects aged = 18 years •Histological or cytological documentation of adenocarcinoma of the colon or rectum •Suitable to receive mFOLFOX6 regimen as first line metastatic treatment •At least 1 measurable lesion as per RECIST version 1.1 •Unresectable or unlikely becoming resectable metastatic disease •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 •Life expectancy of at least 3 months •Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to first dose of study treatment •Total bilirubin = 1.5 x the upper limit of normal (ULN) •Alanine transaminase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (= 5 x ULN for subjects with liver involvement of their cancer) •Lipase = 1.5 x the ULN •Serum creatinine = 1.5 x the ULN •Glomerular filtration rate (GFR) = 60 mL/min/1.73 m2 according to the modified diet in renal disease (MDRD) abbreviated formula •International normalized ratio (INR)/partial thromboplastin time (PTT) = 1.5 x ULN. (Subjects who are being therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in this parameter exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is predose as defined by the local standard of care.) •Platelet count = 100000/mm3, hemoglobin (Hb) = 9 g/dl, absolute neutrophil count (ANC) = 1500/mm3 •Alkaline phosphatase limit = 2.5 x ULN (= 5 x ULN for subjects with liver involvement of their cancer) •Persistent proteinuria of CTC Grade 3 or higher (> 3.5g / 24 hrs, measured by urine protein: creatinine ration on a random urine sample) •Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment. •Women of childbearing potential and men must agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) since signing of the informed consent form until at least 6 months after the last study treatment administration. The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. •Signed informed consent must be obtained before any study specific procedure. Subjects must be able to understand and willing to sign the written informed consent. 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 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: •Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter the study. •Prior systemic anticancer therapy for metastatic CRC. Adjuvant chemotherapy for CRC (Stage I, II, III) is permitted, if the adjuvant therapy ended > 6 months before screening and recurrent disease was documented. •Prior treatment with antivascular endothelial growth factor (anti-VEGF) agents and any signal transduction inhibitors (STIs) •Previous or concurrent cancer that is distinct in primary site or histology from CRC within 5 years prior to screening, EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [Non invasive tumor], Tis [Carcinoma in situ] and T1 [Tumor invades lamina propria]). •Pregnant or breastfeeding subjects. Women of childbearing potential not employing adequate contraception or 150 mm Hg or diastolic pressure > 90 mm Hg despite optimal medical management) •Subjects with phaeochromocytoma •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study treatment •Ongoing infection > Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). •Known history of human immunodeficiency virus (HIV) infection •Active or chronic hepatitis B or C infection with a need for antiviral treatment •Subjects with symptoms, signs, or history of brain metastases (in the case of suspected brain metastases, a cranial CT/MRI is required to exclude brain metastases) •History of organ allograft •Subjects with evidence or history of bleeding diathesis. •Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks of start of study treatment •Nonhealing wound, ulcer, or bone fracture •Renal failure requiring hemo-or peritoneal dialysis •Dehydration = CTCAE Grade 1 •Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results •Known hypersensitivity to any drug of study treatment, study drug classes, or excipients in the formulation •Any illness or medical conditions that are unstable or could jeopardize the safety of the subject and his/her compliance in the study •Interstitial lung disease with ongoing signs and symptoms at the time of informed consent •Subjects unable to swallow oral medications •Any malabsorption condition •Close affiliation with the investigational site (eg
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Objective tumor response rate (ORR), centrally assessed; Secondary Objective: •Overall survival (OS) •Progression-free survival (PFS), centrally assessed •Disease control rate (DCR), centrally assessed •Duration of response (DOR) and stable disease (SD), centrally assessed ; Primary end point(s): Objective tumor response rate (ORR) based on blinded central radiological review of all tumor evaluations is the primary end point of the study. The study is planned according to the fixed-sample design for proving efficacy. The aim is to show that therapy with mFOLFOX6 for colorectal cancer in combination with regorafenib improves the response rate observed for the standard therapy alone. The response rate for the standard therapy is assumed to be 40%. The design specifications are as follows: one-sided type I error level = 10% , power = 90% (type II error rate = 10%), and "response rate for standard therapy" p0= 0.40 (null hypothesis), where the one-sided type I error level is the probability of rejecting the null hypothesis if the true response rate is less than or equal to 40% and 1-power is the probability of rejecting the alternative hypothesis if the true response rate is greater 40%. For the power calculation it is assumed, that under the alternative hypothesis the expected response rate for combination therapy may be 60%, ie, p1 = 0.6. These specifications result in the total sample size of 41 patients. The final analysis of efficacy will be performed after the last subject included into the treatment phase has been treated for at least 6 months. If this last subject discontinues from the study, for any reason, before being treated for 6 months then the preceding subject will be | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: · Overall survival - 30 Jun 2014, or last available date which subject was known to be alive, whichever is earlier. · Progression-free survival - time from date of start of study treatment to date of first observed disease progression or death due to any cause, if death occurs before progression is documented. · Disease control rate - during treatment of within 30 days after termination of study medication. · Duration of response - time from date of first documented objective response of PR or CR, whichever is noted earlier, to first disease progression or death (if death occurs before progression is documented). Stable disease- time (days) from date of start of study treatment to date at which disease progression or death (if death occurs before progression) is first documented ; Secondary end point(s): · Overall survival (OS) · Progression-free survival (PFS), centrally assessed · Disease control rate (DCR), centrally assessed · Duration of response (DOR) and stable disease (SD), centrally assessed | — |
Countries
Australia, Belgium, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer Healthcare AG
Outcome results
None listed