Open-label, single arm trial of BI 695502 in patients with previously untreated locally advanced or metastatic colorectal cancer
- Conditions
- Previously untreated locally advanced or metastaticcolorectal cancerMedDRA version: 18.1Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003718-25-ES
- Lead Sponsor
- Boehringer Ingelheim International GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
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 <2 g in 24 hours or an equivalent protein/creatinine ratio of <2000 mg/g creatinine (or <226.0 mg/mmol creatinine)
7. Life expectancy ?12 months based on clinical judgment.
8. For participants of reproductive potential (males and females), use of a medically acceptable method of contraception during the trial, i.e., a combination of two forms of effective contraception (defined as hormonal contraception, intrauterine device,condom with spermicide, etc). All subjects (males and females of childbearing potential) must also agree to use an acceptable method of contraception (see above) for 6 months following completion or discontinuation from the trial medication. Females will be defined as of childbearing potential if they have not undergone a permanent contraceptive operation or they are not postmenopausal. Permanent contraceptive operation is defined as: hysterectomy, hysterosalpingectomy, or bilateral oophorectomy. The status of a female should be considered as postmenopausal when she has not had a period for 12 consecutive months without an alternative medical cause.
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method