Induction FOLFOX with or without Aflibercept followed by chemoradiation in High Risk Locally Advanced Rectal Cancer. Phase II randomized, multicenter, open label trial
- Conditions
- Patients with high risk locally advanced rectal carcinoma (defined by Magnetic Resonance Imaging [MRI]), who are candidates for multimodality treatment.MedDRA version: 17.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002063-14-ES
- Lead Sponsor
- GEMCAD (Grupo Español Multidisciplinar en Cáncer Digestivo)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 180
1) Signed and dated informed consent, and willing and able to comply with protocol requirement;
2) Male or female subjects with rectal cancer = 18 and <70 years of age;
3) High risk MRI-defined operable rectal cancer (with an inferior margin no more than 12 cm above the anal verge as assesed by MRI).
Presence of at least 1 of the following on high resolution, thin-slice MRI (3 mm):
Middle Third Tumors
-mrT3
a) Extramural vascular invasion (EMVI) positive
b) Extramural extension > 5 mms into perirectal fat
c) Mesorectal fascia (MRF) threatened or involved*
-mr T4***
Distal Third Tumors (?5 cm from anal verge)
- mrT3 tumor at or below levators
-T4 as above
N2**
*tumor or lymph node < 1 mm from the mesorectal fascia
**= 4 lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease. = 4 nodes, whether enlarged or not, with a rounded, homogeneous appearance is thus not sufficient.
***T4a: overgrowth to an adjacent organ or structure or T4b: peritoneal involvement.
4) Histologically confirmed adenocarcinoma of the rectum. All other histological types are excluded;
5) ECOG Performance Status of = 1;
6) Hematological status: neutrophils (ANC) = 1.5x109/L; platelets = 100x109/L; hemoglobin = 9g/dL;
7) Adequate renal function: serum creatinine level <1.5 x upper limit of normality (ULN);
8) Adequate liver function: serum bilirubin = 1.5 x ULN, alkaline phosphatase <5xULN, AST/ALT < 3 x ULN;
9) Proteinuria <2+ (dipstick urinalysis) or = 1g/24hour;
10) Regular follow-up feasible;
11) For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior to starting study treatment;
12) Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.
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 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180
1) Prior treatment with aflibercept;
2) History or evidence upon physical examination of metastasis;
3) Uncontrolled hypercalcemia;
4) Pre-existing permanent neuropathy (NCI grade ?2);
5) Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy;
6) Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy);
7) Treatment with any other investigational medicinal product within 28 days prior to study entry;
8) Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years;
9) Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days;
10) Pregnant or breastfeeding women;
11) Patients with known allergy to any excipient to study drugs;
12) History of myocardial infarction and/or stroke within 6 months prior to randomization;
Previous history of stable angina, uncontrolled arrhythmia, and acute coronary syndrome even if controlled with medication or with myocardial infarction within the last 12 months.
13) Bowel obstruction.
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