Rectal Cancer
Conditions
Brief summary
This trial compares induction treatment with FOLFOX with or without aflibercept in a high risk population selected by MRI, prior to receiving standard chemoradiation (capecitabine combined with 50.4 Gy in 28 days) and surgery, in order to evaluate the efficacy in terms of pathologic complete response (pCR).
Detailed description
This is a randomized trial comparing induction treatment with FOLFOX with or without aflibercept in a high risk population selected by MRI, prior to receiving standard chemoradiation (capecitabine combined with 50.4 Gy in 28 days) and surgery. Once it is confirmed that the subjects fulfill the eligibility criteria (MRI-defined high risk RC), and have signed the informed consent, a central review will be requested to confirm clinical stage, and then they will be randomized to receive mFOLFOX6 + Aflibercept or mFOLFOX6 (without Aflibercept). Random assignment of treatment will be stratified by T3 versus T4 stage. All the patients enrolled in the study will receive one cycle of study medication (mFOLFOX6 with or without aflibercept) every 14 days for six cycles, unless unacceptable toxicity or progression is detected. After this treatment, patients will receive standard chemo-radiotherapy (CT/RT) (capecitabine 825 mg/m2 twice daily combined with a total dose of 50.4 Gy in 28 days) followed by surgery, provided they have not progressed. Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment. If a patient withdraws consent and refuses to receive further treatment, the patient must be followed up for 3 years from randomization or until progression, to evaluate disease-free survival. If a patient withdraws consent and refuses to continue in the study, the follow-up evaluations must be discontinued.
Interventions
DRUGAflibercept
Administered I.V. at doses of 4 mg/Kg on Day 1 every 14 days. It will be supplied to sites by Sponsor as 4 ml vials at a concentration of 25 mg/ml
DRUG5-Fluoruracil
Once every 14 days. Day 1: 400 mg/m2 I.V. bolus and a 46 h infusion of 5-FU 2400 mg/m2
DRUGOxaliplatin
Once every 14 days. Day 1: 85 mg/m2 I.V. infusion in 250-500 mL, over two hours, followed by 5-FU
DRUGLeucovorin
Once every 14 days. Day 1: 200 mg/m2 I.V., over two hours, followed by 5-FU
Sponsors
Pivotal S.L.
Grupo Espanol Multidisciplinario del Cancer Digestivo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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 \<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 assessed by MRI). Presence of at least 1 of the following on high resolution, thin-slice MRI (3 mm): Middle Third Tumors * mr T3 1. Extramural vascular invasion (EMVI) positive 2. Extramural extension \> 5 mms into perirectal fat 3. Mesorectal fascia (MRF) threatened or involved\* * mr T4\*\*\* Distal Third Tumors (≤5 cm from anal verge) * mr T3 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. Eastern Cooperative Oncology Group (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 \<5x ULN, 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.
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 | Description |
|---|---|---|
| Number of Patients Achieving Pathologic Complete Response (pCR). | From baseline until 2 years and 2 months | The number of patients achieving pCR after induction therapy with mFOLFOX6 +/- aflibercept followed by chemotherapy (CT)/radiotherapy (RT). pCR will be defined as the absence of viable tumor cells in the primary tumor and in the lymph nodes (T0N0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | From baseline until 2 years and 2 months | R0 resection is defined as complete tumor removal, and correlates with good prognosis. Tumor regression grade (TRG) is defined as presence of residual tumor after preoperative therapy. This was assessed by magnetic resonance imaging (MRI) according to the 5-point regression grading scale established by Mandard: TRG1 (complete response with no residual cancer), TRG2 (rare residual cancer), TRG3 (fibrosis outgrowing residual cancer), TRG4 (residual cancer outgrowing fibrosis) and TRG5 (absence of regression). Circular Radial Margin (CRM) is defined as the distance from the margin of normal tissue to the edge of tumor tissue in the resected primary tumor the measured by histopathology study after surgery. A margin of ≤1 mm is considered to be a negative prognostic factor for local recurrence. |
| Number of Participants With Significant MRI Changes Post Intervention, as Defined by T Downstaging | From baseline until 2 years and 2 months | Tumor size is assessed by MRI to determine the T stage. T Downstaging: defined as a lower pathologic T stage compared to pre-treatment T stage. |
| Number of Patients Reporting Adverse Events (AEs) | From baseline until 2 years and 2 months | The safety and tolerability of the study therapy were assessed by means of AEs and changes in laboratory data. AEs were coded and evaluated using the NCI-CTCAE v4.0 toxicity criteria (if NCI-CTCAE are not applicable, MedDRA was used). |
| Number of Patients Reporting Surgical Complications | From surgical intervention up to 30 days post-surgery, within a general time frame of 2 years and 2 months per study protocol | Surgical complications will be assessed by means of AEs reported during 30 days post surgery. |
| Disease Free Survival (DFS) Rate at 3 Years | At 3 years after study treatment completion, within a general time frame of 5 years and two months | DFS rate is defined as the percentage of participants without local recurrences at 3-years post study treatment. Here we report the DFS rate at 3-years after completing the Study treatment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| mFOLFOX6 + Aflibercept \- mFOLFOX-6 scheme: 5-Fluoruracil \[5-FU\], oxaliplatin and leucovorin will be administered intravenously once every 14 days according to mFOLFOX-6 scheme:
Day 1: Oxaliplatin 85 mg/m² IV infusion in 250-500 mL and leucovorin 200 mg/m² IV, both over two hours, followed by 5-FU 400 mg/m² IV bolus and a 46 h infusion of 5-FU 2400 mg/m².
\- Aflibercept, will be administered intravenously (I.V.) at doses of 4 mg/Kg on Day 1 every 14 days. Aflibercept will be supplied to sites by the study Sponsor as 4 ml vials at a concentration of 25 mg/ml.
Treatment will continue until six cycles are administered unless unacceptable toxicity or progression occurs.
Aflibercept: Administered I.V. at doses of 4 mg/Kg on Day 1 every 14 days. It will be supplied to sites by Sponsor as 4 ml vials at a concentration of 25 mg/ml
5-Fluoruracil: Once every 14 days. Day 1: 400 mg/m2 I.V. bolus and a 46 h infusion of 5-FU 2400 mg/m2
Oxaliplatin: Once every 14 days. Day 1: 85 mg/m2 I.V. infusion in 250-500 mL, over two hours, followed by 5-FU
Leucovorin: Once every 14 days. Day 1: 200 mg/m2 I.V., over two hours, followed by 5-FU | 115 |
| mFOLFOX6 \- mFOLFOX-6 scheme: 5-Fluoruracil \[5-FU\], oxaliplatin and leucovorin will be administered intravenously once every 14 days according to mFOLFOX-6 scheme:
Day 1: Oxaliplatin 85 mg/m² IV infusion in 250-500 mL and leucovorin 200 mg/m² IV, both over two hours, followed by 5-FU 400 mg/m² IV bolus and a 46 h infusion of 5-FU 2400 mg/m².
Treatment will continue until six cycles are administered unless unacceptable toxicity or progression occurs.
5-Fluoruracil: Once every 14 days. Day 1: 400 mg/m2 I.V. bolus and a 46 h infusion of 5-FU 2400 mg/m2
Oxaliplatin: Once every 14 days. Day 1: 85 mg/m2 I.V. infusion in 250-500 mL, over two hours, followed by 5-FU
Leucovorin: Once every 14 days. Day 1: 200 mg/m2 I.V., over two hours, followed by 5-FU | 65 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Death | 3 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progression disease | 6 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | mFOLFOX6 + Aflibercept | mFOLFOX6 | Total |
|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 10.4 | 62.2 years STANDARD_DEVIATION 9.2 | 59.7 years STANDARD_DEVIATION 10 |
| Clinical stage Tumor-nodes-metastasis (TNM) Mising | 1 Participants | 1 Participants | 2 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT2 | 1 Participants | 0 Participants | 1 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT3 | 17 Participants | 12 Participants | 29 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT3A | 1 Participants | 0 Participants | 1 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT3B | 8 Participants | 8 Participants | 16 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT3C | 47 Participants | 22 Participants | 69 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT3D | 7 Participants | 4 Participants | 11 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT4 | 9 Participants | 6 Participants | 15 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT4A | 16 Participants | 7 Participants | 23 Participants |
| Clinical stage Tumor-nodes-metastasis (TNM) mrT4B | 8 Participants | 5 Participants | 13 Participants |
| Count of Patients Which Had a Baseline Clinical Stage TNM Nodes (n2) | 115 Participants | 65 Participants | 180 Participants |
| EMVI score Score 0/1/2 | 60 Participants | 34 Participants | 94 Participants |
| EMVI score Score 3/4 | 55 Participants | 31 Participants | 86 Participants |
| Histology Adenocarcinoma | 115 Participants | 65 Participants | 180 Participants |
| Histology other | 0 Participants | 0 Participants | 0 Participants |
| Location Distal | 30 Participants | 18 Participants | 48 Participants |
| Location Middle | 84 Participants | 46 Participants | 130 Participants |
| Location Missing | 1 Participants | 1 Participants | 2 Participants |
| Mesorectal Fascia (FMR) FMR + (distance <=1 mm) | 68 Participants | 37 Participants | 105 Participants |
| Mesorectal Fascia (FMR) NR | 47 Participants | 28 Participants | 75 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Spain | 115 Participants | 65 Participants | 180 Participants |
| Sex: Female, Male Female | 38 Participants | 26 Participants | 64 Participants |
| Sex: Female, Male Male | 77 Participants | 39 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 115 | 7 / 65 |
| other Total, other adverse events | 115 / 115 | 65 / 65 |
| serious Total, serious adverse events | 45 / 115 | 16 / 65 |
Outcome results
Primary
Number of Patients Achieving Pathologic Complete Response (pCR).
The number of patients achieving pCR after induction therapy with mFOLFOX6 +/- aflibercept followed by chemotherapy (CT)/radiotherapy (RT). pCR will be defined as the absence of viable tumor cells in the primary tumor and in the lymph nodes (T0N0)
Time frame: From baseline until 2 years and 2 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathologic Complete Response (pCR). | Yes | 25 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathologic Complete Response (pCR). | No | 90 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathologic Complete Response (pCR). | Yes | 9 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathologic Complete Response (pCR). | No | 56 Participants |
Secondary
Disease Free Survival (DFS) Rate at 3 Years
DFS rate is defined as the percentage of participants without local recurrences at 3-years post study treatment. Here we report the DFS rate at 3-years after completing the Study treatment.
Time frame: At 3 years after study treatment completion, within a general time frame of 5 years and two months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| mFOLFOX6 + Aflibercept | Disease Free Survival (DFS) Rate at 3 Years | 75.2 percentage of participants |
| mFOLFOX6 | Disease Free Survival (DFS) Rate at 3 Years | 81.5 percentage of participants |
Secondary
Number of Participants With Significant MRI Changes Post Intervention, as Defined by T Downstaging
Tumor size is assessed by MRI to determine the T stage. T Downstaging: defined as a lower pathologic T stage compared to pre-treatment T stage.
Time frame: From baseline until 2 years and 2 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| mFOLFOX6 + Aflibercept | Number of Participants With Significant MRI Changes Post Intervention, as Defined by T Downstaging | Yes | 68 Participants |
| mFOLFOX6 + Aflibercept | Number of Participants With Significant MRI Changes Post Intervention, as Defined by T Downstaging | No | 47 Participants |
| mFOLFOX6 | Number of Participants With Significant MRI Changes Post Intervention, as Defined by T Downstaging | Yes | 46 Participants |
| mFOLFOX6 | Number of Participants With Significant MRI Changes Post Intervention, as Defined by T Downstaging | No | 19 Participants |
Secondary
Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate
R0 resection is defined as complete tumor removal, and correlates with good prognosis. Tumor regression grade (TRG) is defined as presence of residual tumor after preoperative therapy. This was assessed by magnetic resonance imaging (MRI) according to the 5-point regression grading scale established by Mandard: TRG1 (complete response with no residual cancer), TRG2 (rare residual cancer), TRG3 (fibrosis outgrowing residual cancer), TRG4 (residual cancer outgrowing fibrosis) and TRG5 (absence of regression). Circular Radial Margin (CRM) is defined as the distance from the margin of normal tissue to the edge of tumor tissue in the resected primary tumor the measured by histopathology study after surgery. A margin of ≤1 mm is considered to be a negative prognostic factor for local recurrence.
Time frame: From baseline until 2 years and 2 months
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | R0 rate | No | 2 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | TRG1-2 | Not available | 0 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | TRG1-2 | Yes | 59 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | CRM ≤ 1 | Yes | 3 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | R0 rate | Not available | 12 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | CRM ≤ 1 | No | 96 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | TRG1-2 | No | 56 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | CRM ≤ 1 | Not available | 16 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | R0 rate | Yes | 101 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | CRM ≤ 1 | Not available | 6 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | R0 rate | Yes | 60 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | R0 rate | No | 2 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | R0 rate | Not available | 3 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | TRG1-2 | Yes | 30 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | TRG1-2 | No | 35 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | TRG1-2 | Not available | 0 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | CRM ≤ 1 | Yes | 3 Participants |
| mFOLFOX6 | Number of Patients Achieving Pathological Parameters of Efficacy: R0 Resection, Tumor Regression Grade, and Circular Radial Margin Rate | CRM ≤ 1 | No | 56 Participants |
Secondary
Number of Patients Reporting Adverse Events (AEs)
The safety and tolerability of the study therapy were assessed by means of AEs and changes in laboratory data. AEs were coded and evaluated using the NCI-CTCAE v4.0 toxicity criteria (if NCI-CTCAE are not applicable, MedDRA was used).
Time frame: From baseline until 2 years and 2 months
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE | Yes | 105 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to treatment discontinuation | No | 95 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE | No | 10 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one AE | No | 0 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE Grade 3-4 | Yes | 64 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to death | Yes | 3 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE Grade 3-4 | No | 51 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one Grade 3-4 AE | No | 32 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to death | Yes | 0 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to death | No | 112 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to death | No | 115 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one AE | Yes | 115 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to permanent treatment discontinuation | Yes | 17 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one Serious Adverse Event (SAE) | Yes | 45 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to permanent treatment discontinuation | No | 98 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to treatment discontinuation | Yes | 20 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related Serious Adverse Event (SAE) | Yes | 25 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one Serious Adverse Event (SAE) | No | 70 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related Serious Adverse Event (SAE) | No | 90 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Adverse Events (AEs) | At least one Grade 3-4 AE | Yes | 83 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related Serious Adverse Event (SAE) | No | 62 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one AE | No | 0 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one Grade 3-4 AE | Yes | 31 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one Grade 3-4 AE | No | 34 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to treatment discontinuation | Yes | 4 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to treatment discontinuation | No | 61 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to death | Yes | 0 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one AE that lead to death | No | 65 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one Serious Adverse Event (SAE) | Yes | 16 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one Serious Adverse Event (SAE) | No | 49 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE | Yes | 59 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE | No | 6 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE Grade 3-4 | Yes | 17 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE Grade 3-4 | No | 48 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to death | Yes | 0 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to death | No | 65 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to permanent treatment discontinuation | Yes | 3 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related AE that led to permanent treatment discontinuation | No | 62 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one treatment-related Serious Adverse Event (SAE) | Yes | 3 Participants |
| mFOLFOX6 | Number of Patients Reporting Adverse Events (AEs) | At least one AE | Yes | 65 Participants |
Secondary
Number of Patients Reporting Surgical Complications
Surgical complications will be assessed by means of AEs reported during 30 days post surgery.
Time frame: From surgical intervention up to 30 days post-surgery, within a general time frame of 2 years and 2 months per study protocol
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Postoperative AEs | Yes | 3 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | wound infection | Yes | 5 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Complications | Yes | 60 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | wound infection | No | 110 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Postoperative AEs Grade 3-4 | Yes | 2 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | intraabdominal infection | Yes | 10 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Complications | No | 55 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | intraabdominal infection | No | 105 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Postoperative AEs | No | 112 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Stoma complications | Yes | 2 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Stoma complications | No | 113 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Anastomosis fistula | Yes | 4 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Reoperation | Yes | 9 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Postoperative AEs Grade 3-4 | No | 113 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Reoperation | No | 106 Participants |
| mFOLFOX6 + Aflibercept | Number of Patients Reporting Surgical Complications | Anastomosis fistula | No | 111 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Reoperation | No | 60 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Postoperative AEs | Yes | 1 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Postoperative AEs | No | 64 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Postoperative AEs Grade 3-4 | Yes | 0 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Postoperative AEs Grade 3-4 | No | 65 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Complications | Yes | 30 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Complications | No | 35 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Anastomosis fistula | Yes | 1 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Anastomosis fistula | No | 64 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | wound infection | Yes | 5 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | wound infection | No | 60 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | intraabdominal infection | Yes | 1 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | intraabdominal infection | No | 64 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Stoma complications | No | 65 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Reoperation | Yes | 5 Participants |
| mFOLFOX6 | Number of Patients Reporting Surgical Complications | Stoma complications | Yes | 0 Participants |