Locally advanced or metastatic Colorectal Cancer MedDRA version: 9.1 Level: PT Classification code 10061451 Term: Colorectal cancer
Conditions
Sponsors
Eli Lilly and Company limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the following criteria: [1] Histologic diagnosis of locally advanced or metastatic CRC that is not amenable to curative therapy. The histology types to be included are adenocarcinoma, mucinous adenocarcinoma, signet ring, and undifferentiated. Patients with neuroendocrine carcinomas will be excluded. [2] Performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group scale (Protocol Attachment S064.4; Oken et al. 1982). [3] Received 6 cycles (3 months [12 weeks]) of first-line therapy with FOLFOX or FOLFIRI, plus bevacizumab for metastatic CRC. Patients who received 6 cycles of first-line therapy with FOLFOX or FOLFIRI, plus bevacizumab for recurrent CRC that has relapsed at least 12 months after completion of adjuvant therapy will also be included. All standard FOLFOX (for example, de Gramont et al. 2000) or FOLFIRI (for example, Tournigand et al. 2004) regimens given on a biweekly schedule will be permitted; however, 21-day regimens will not be allowed. [4] Prior radiotherapy must be completed 30 days before beginning first-line therapy. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). [5] No more than 4 weeks may pass between the end of first-line therapy (that is, Day 14 of Cycle 6) and randomization. [6] Documented evidence of tumor response of CR, PR, or SD by computed tomography (CT) scan or magnetic resonance imaging (MRI). Confirmation of response is not required. Baseline tumor assessment must occur between Cycle 6 (Day 1) of first-line therapy and the date of randomization. The first dose of study treatment should be administered within 6 weeks after the baseline scan. [7] Adequate organ function including the following: Adequate bone marrow reserve: white blood cell count >3.0 x 109/L, absolute neutrophil count >1.5 x 109/L, platelet count >100 x 109/L, and hemoglobin >9.0 g/dL (>5.6 mmol/L). Hepatic: bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria: [13] Are unable to swallow tablets. [14] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [15] Are unable to discontinue use of enzyme inducing anti-epileptic drugs (EIAEDs), such as phenytoin, carbamazepine, or phenobarbital (refer to Section 5.7.1). [16] Have a prior malignancy (other than CRC or adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer), unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. [17] Are pregnant or lactating. [18] Are receiving concurrent administration of any other antitumor therapy. [19] Have known hypersensitivity to any component of enzastaurin. [20] Have a serious concomitant systemic disorder (for example, active infection including known HIV) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. [21] Have a serious cardiac condition, such as myocardial infarction within the last 6 months, angina, unstable coronary artery disease, known arterial thrombosis, or heart disease, as defined by the New York Heart Association Class II, III or IV (Protocol Attachment S064.5; Bruce 1956). [22] Have known central nervous system metastases. A screening CT or MRI before enrollment in the absence of a clinical suspicion of brain metastases is not required. [23] Have inadequately controlled hypertension (defined as systolic blood pressure >140 and/or diastolic >90 mm Hg on antihypertensive medications). [24] Have any prior history of hypertensive crisis or hypertensive encephalopathy. [25] Have evidence of bleeding diathesis or coagulopathy. [26] Have had major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization or have an anticipated need for major surgery during the course of the study. [27] Have had a core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment. [28] Have a serious, nonhealing wound, ulcer, or bone fracture. [29] Have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry. [30] History of stroke or transient ischemic attack within 6 months prior to randomization. [31] Have significant vascular disease (such as aortic aneurysm or aortic dissection) or symptomatic peripheral vascular disease. [32] Have proteinuria at baseline, as demonstrated by either: • urine dipstick for proteinuria >2+. Patients discovered to have >2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate 1.0 at baseline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare Arm A versus Arm B in terms of PFS measured from the time of randomization after completing 6 cycles of first-line therapy for metastatic CRC: • Arm A: 5-FU/LV plus bevacizumab in combination with enzastaurin • Arm B: 5-FU/LV plus bevacizumab in combination with placebo.;Secondary Objective: The secondary objectives are: • to compare the following between treatment arms: • OS from the time of randomization • OS and PFS from the start of first-line therapy. • to assess the safety and AE profile in both treatment arms using Common Terminology Criteria for Adverse Events (CTCAE Version 3.0, NCI 2006).;Primary end point(s): The primary endpoint is PFS measured from time of randomization. Secondary efficacy endpoints include assessment of OS from randomization, and OS and PFS from start of first-line therapy. | — |
Countries
Austria, France, Germany, Italy
Outcome results
None listed