Previously untreated locally advanced or metastaticcolorectal cancer MedDRA version: 18.1 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: PT Classifi
Conditions
Interventions
Product Name: BI 695502
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BI 695502
Other descriptive name: BI 695502
Concentration unit: mg/l milligram(s)/litre
Concentr
Sponsors
Boehringer Ingelheim International GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged ?18 years (for Japan only: Age ?20 years at Visit 1) with histologically confirmed mCRC. 2. All patients must sign and date an Informed Consent Form consistent with ICH GCP guidelines and local legislation prior to participation in the trial (i.e., prior to any trial procedures, which include medication washout and restrictions) and be willing tofollow the CTP. 3. Locally advanced or metastatic disease not amenable to surgical curative treatment and eligible to receive therapy with mFOLFOX6 + bevacizumab. 4. At least one measurable lesion according to RECIST 1.1. 5. ECOG PS 0 or 1. 6. Adequate hepatic, renal and bone marrow function: a. Serum creatinine ?1.5 x upper limit of normal (ULN) or a creatinine clearance of ?50 mL/min calculated by Cockcroft-Gault formula. b. Absolute neutrophil count >1.5 x109/L. c. Platelet count >100 x109/L. d. Hemoglobin ?9 g/dL (without transfusion within 2 weeks prior to randomization). e. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ?2.5 x ULN. If liver metastases are present, ALT or AST ?5 x ULN. f. Alkaline phosphatase ?2.5 x ULN (?5 x ULN in the presence of hepatic and/or bone metastases). g. Serum bilirubin ?1.5 x ULN, except in the case of known Gilbert's Syndrome. h. International normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits. i. Proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Prior systemic therapy for metastatic disease. Any adjuvant/neoadjuvant therapy must have been completed >12 months prior to screening. 2. Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including Avastin® or Avastin® biosimilars. 3. Previous malignancy other than CRC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix. 4. Known or symptomatic brain metastasis. 5. Any unresolved toxicity > Common Toxicity Criteria Grade 1 (except alopecia) from previous anticancer therapy (including radiotherapy). 6. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. 7. A thrombotic or hemorrhagic event ?6 months prior to screening (includes hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, vaginal bleeding, cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and coronary artery disease). 8. History of myocardial infarction (?6 months prior to screening), unstable angina, New York Heart Association Grade II or greater, congestive heart failure, or serious cardiac arrhythmia requiring medication. 9. Current or recent (within 10 days of first dose of BI 695502) regular use of aspirin (>325 mg/day) or other non-steroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity or treatment with dipyramidole, ticlopidine, clopidogrel and cilostazol. 10. Current treatment with oral, inhaled or topical corticosteroids; the dose must not exceed 10 mg/day prednisolone or equivalent. During the 4 weeks prior to Day 1, the dose must be stable. 11. Current or recent (within 10 days of first dose of BI 695502) use of full-dose oral or parenteral anticoagulants or other thrombolytic agents for therapeutic (as opposed to prophylactic) purposes, clinically serious (as judged by the Investigator) non-healing wounds, or incompletely healed bone fracture. 12. Patients who are expecting to receive any live vaccine or bacterial vaccinations during the trial, or receive one up to 3 months prior to the first dose of trial medication. 13. Patients with a history of poorly controlled hypertension or with resting blood pressure >150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy 14. Any surgical procedure within 28 days of first dose of BI 695502 or anticipated elective surgery during the trial (see Table 4.2.2.1: 1 for details). 15. History of active gastroduodenal ulcer(s). 16. History of abdominal fistula as well as non-GI fistula, GI perforation or intra-abdominal abscess within 6 months prior to screening. 17. Active or chronic hepatitis B or C, ongoing human immunodeficiency virus (HIV) infection, or tuberculosis (TB) (see Section 5.3.3). Screening for HIV and TB to be performed according to local practice and local regulatory guidance. 18. Treatment in a clinical trial within 4 weeks prior to initiation of trial treatment. Patients who have received treatment with a drug that has not received regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives, whichever is longer, of the initial dose of trial medication. 19. Patient considered unsuitable for inclusion by the Investigator (e.g., inability to understand and/or comply with study requirements or presence of any condition which, in the opinion of the Investigator, would not allow safe participation in the study). 20. Known hypersensitivity to the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to evaluate the safety and tolerability of BI 695502 in combination with leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) and as maintenance therapy (when applicable).;Secondary Objective: Secondary objectives: To evaluate the following efficacy parameters: Progression-free survival (PFS), objective response rate (proportion of patients with complete response [CR] plus partial response [PR]), overall survival (OS), duration of response (DOR), time to progression (TTP). Further objectives: To evaluate the pharmacokinetics (PK) of BI 695502 and its correlation with antidrug antibodies (ADAs)/neutralizing antidrug antibodies (nADAs) in colorectal cancer patients To evaluate the presence of ADAs and nADAs.;Primary end point(s): The primary safety endpoint of the trial is patients with any of the following selected AEs: - Anaphylactic reactions/hypersensitivity reactions/infusion-related reactions. - Thromboembolic events: Arterial, Venous - GI perforations - Hypertension - Proteinuria - Pulmonary hemorrhage - All hemorrhages and pulmonary hemorrhages - Wound-healing complications including abscess and fistulas - Posterior reversible encephalopathy syndrome - Ovarian failure;Timepoint(s) of evaluation of this end point: AEs may occur at any time | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints of the trial are: - PFS is defined as the time from first administration of trial medication until disease progression as assessed by central imaging review according to RECIST 1.1 or death of any cause. - Objective Response according to RECIST 1.1 as assessed by central imaging review. - DOR defined as the time from first documented CR or PR until time of progression as assessed by central imaging review. - TTP defined as the time from first administration of trial medication to the date of tumor progression as assessed by central imaging review. - OS defined as the time from first administration of trial medication until death from any cause.;Timepoint(s) of evaluation of this end point: At every cycle | — |
Countries
Chile, Germany, Japan, Spain, Ukraine, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed