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: 100000004864
Conditions
Interventions
Trade Name: ZALTRAP
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: aflibercept
CAS Number: 862111-32-8
Sponsors
GEMCAD (Grupo Español Multidisciplinar en Cáncer Digestivo)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 =65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of induction therapy with mFOLFOX6 +/- aflibercept followed by CT/RT in terms of pathological Complete Responses (pCR); Secondary Objective: - To evaluate pathological parameters of efficacy: R0 resection, TRG, and positive or negative CRM rate. - To evaluate the relationship between MRI changes with outcome. - To further characterize the safety and tolerability of mFOLFOX6 +/- aflibercept followed chemoradiation. - To determine the rate of 30 days surgical complications. - To evaluate the 3 years local recurrence and DFS. - To determine the levels of tumor biomarkers expression at baseline and correlate them with response to treatment with mFOLFOX6 + aflibercept. ;Primary end point(s): To analyze the number of patients achieving pCR after induction therapy with mFOLFOX6 +/- aflibercept followed by CT/RT. pCR will be defined as the absence of viable tumor cells in the primary tumor and in the lymph nodes (ypT0N0); Timepoint(s) of evaluation of this end point: Two interim analysis will be done to evaluate safety, futility/efficacy: - At 33% of the sample size - At 66% of the sample size Final analysis will be done at 100% of the sample size (180 patients) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To determine CRM negative and R0 resection rates. - TRG; residual tumor after preoperative therapy will be semiquantitatively evaluated according to the 5-point regression grading scale established by Mandard. Involvement of the histologic CRM will be defined as tumor = 2 mm from the resection margin. - T Downstaging: defined as a lower pathologic T stage compared to pre-treatment mrT stage - The safety and tolerability of the study therapy will be assessed by means of AEs and changes in laboratory data. AEs will be coded and evaluated using the NCI-CTCAE v4.0 toxicity criteria (if NCI-CTCAE are not applicable, MedDRA will be used). - Surgical complications will be assessed by means of AEs reported during 30 days post surgery. - To determine the rate of local recurrence and DFS at 3-years. - To determine the levels of tumor biomarkers expression at baseline in serum and biopsy and correlate them with MRI tumor regression and pathological response to treatment with mFOLFOX6 + aflibercept and relapse and survival outcomes ; Timepoint(s) of evaluation of this end point: Two interim analysis will be done to evaluate safety, futility/efficacy: - At 33% of the sample size - At 66% of the sample size Final analysis will be done at 100% of the sample size (180 patients) | — |
Countries
Spain
Contacts
Public ContactMyriam García Iglesias
PIVOTAL, S.L
Outcome results
None listed