Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Pivotal S.L. | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mFOLFOX6 + Aflibercept | Experimental | - 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. |
|
| mFOLFOX6 | Active Comparator | - 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aflibercept | Drug | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | From baseline until 2 years and 2 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Signed and dated informed consent, and willing and able to comply with protocol requirement;
Male or female subjects with rectal cancer ≥18 and <70 years of age;
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
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.
Histologically confirmed adenocarcinoma of the rectum. All other histological types are excluded;
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1;
Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; hemoglobin ≥9g/dL;
Adequate renal function: serum creatinine level <1.5 x upper limit of normality (ULN);
Adequate liver function: serum bilirubin ≤1.5 x ULN, alkaline phosphatase <5x ULN, AST/ALT < 3 x ULN;
Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour;
Regular follow-up feasible;
For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior to starting study treatment;
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:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Carlos Fernández-Martos, MD | Fundación Instituto Valenciano de OncologÃa | Study Director |
| Antonieta Salud Salvia, MD | Hospital Universitari Arnau de Vilanova de Lleida | Principal Investigator |
| Carles Pericay Pijaume, MD | Hospital de Sabadell - Parc Taulà | Principal Investigator |
| Clara Montagut, MD | Hospital del Mar | Principal Investigator |
| Joan Maurel Santasusana, MD | Hospital Clinic of Barcelona | Principal Investigator |
| Vicente Alonso Orduña, MD | Hospital Miguel Servet | Principal Investigator |
| Ruth Vera GarcÃa, MD | Complejo Hospitalario de Navarra | Principal Investigator |
| Javier Gallego Plazas, MD | Hospital General Universitario de Elche | Principal Investigator |
| Núria RodrÃguez Salas, MD | Hospital Universitario La Paz | Principal Investigator |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31465088 | Derived | Fernandez-Martos C, Pericay C, Losa F, Garcia-Carbonero R, Layos L, Rodriguez-Salas N, Martin-Richard M, Alonso-Orduna V, Vera R, Gallego J, Capdevila J, Salud A, Nogue M, Maurel J, Guash I, Montagut C, Lopez C, Macias I, Jain RK, Garcia-Albeniz X. Effect of Aflibercept Plus Modified FOLFOX6 Induction Chemotherapy Before Standard Chemoradiotherapy and Surgery in Patients With High-Risk Rectal Adenocarcinoma: The GEMCAD 1402 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1566-1573. doi: 10.1001/jamaoncol.2019.2294. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age in years, expressed as "Mean (Standard Deviation)" |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | Posted | Count of Participants | Participants | From baseline until 2 years and 2 months |
|
From Baseline to study completion, within an general time frame of 3 years per study protocol
For the statistical tables, adverse events have been coded according to the Medical Dictionary of Regulatory Activities (MedDRA 20.1) system. Their intensity has been coded by (NCI-CTCAE) v4.0 toxicity criteria.
The safety and tolerability of the study therapy were assessed by means of AEs and changes in laboratory data that were reported in the AEs page.
Grade 3 or higher AEs were reported as serious. All the grade 1 and 2 as non serious.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA 20.1 | Systematic Assessment |
There are no overall limitations and caveats. In detail: There were 6 patients that received treatment doses that did not matched protocol specifications. These were notified as protocol major deviations to the competent authorities and ethics committees. The effect of these deviations on results is not significant.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pau Doñate Macian | MFAR Clinical Research | 0034934344412 | investigacion@mfar.net |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 9, 2015 | Mar 10, 2021 | Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C533178 | aflibercept |
| D005472 | Fluorouracil |
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| ID | Term |
|---|---|
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 5-Fluoruracil | Drug | Once every 14 days. Day 1: 400 mg/m2 I.V. bolus and a 46 h infusion of 5-FU 2400 mg/m2 |
|
|
| Oxaliplatin | Drug | Once every 14 days. Day 1: 85 mg/m2 I.V. infusion in 250-500 mL, over two hours, followed by 5-FU |
|
|
| Leucovorin | Drug | Once every 14 days. Day 1: 200 mg/m2 I.V., over two hours, followed by 5-FU |
|
|
| From baseline until 2 years and 2 months |
| 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. | From baseline until 2 years and 2 months |
| 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). | From baseline until 2 years and 2 months |
| Number of Patients Reporting Surgical Complications | Surgical complications will be assessed by means of AEs reported during 30 days post surgery. | From surgical intervention up to 30 days post-surgery, within a general time frame of 2 years and 2 months per study protocol |
| 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. | At 3 years after study treatment completion, within a general time frame of 5 years and two months |
| Antonio Cubillo, MD | Hospital Universitario Madrid Sanchinarro (CIOCC) | Principal Investigator |
| Bertomeu Massuti, MD | Hospital General Universitario de Alicante | Principal Investigator |
| Ferrán Losa, MD | Hospital de Sant Joan Despà Moisés Broggi | Principal Investigator |
| Miguel Nogué, MD | Hospital General de Granollers | Principal Investigator |
| Jaume Capdevila, MD | Hospital Universitari Vall d'Hebrón | Principal Investigator |
| Isabel Busquier, MD | Consorcio Hospitalario Provincial de Castellón | Principal Investigator |
| Inma Guash Jordan, MD | Fundación Althaia Manresa | Principal Investigator |
| Laura Layos Romero, MD | Hospital Universitari Germans Trias i Pujol de Badalona | Principal Investigator |
| Marta MartÃn-Richard, MD | Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau | Principal Investigator |
| Rocio GarcÃa Carbonero, MD | Hospital Universitario 12 de Octubre | Principal Investigator |
| Carlos López López, MD | Hospital Universitario Marqués de Valdecilla | Principal Investigator |
| Progression disease |
|
| Death |
|
| Physician Decision |
|
| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Country of recruitment | Count of Participants | Participants | No |
|
| Clinical stage Tumor-nodes-metastasis (TNM) | TNM clinical stage assessed by magnetic resonance (mr). The T refers to the size and extent of the main tumor. Categories assessed by mr: T2: limited to bowel wall T3: beyond muscularis propia T3A: <1 mm beyond muscularis propia T3B: 1-5 mm beyond muscularis propia T3C: 5-15 mm beyond muscularis propia T4: involvement peritoneal reflection T4A: involvement peritoneal reflection T4B: ingrowth in organ | Count of Participants | Participants |
|
| Count of Patients Which Had a Baseline Clinical Stage TNM Nodes (n2) | Used to describe regional lymph node involvement of the tumor. N0 indicates no regional nodal spread, while N1-N3 indicates some degree of nodal spread, with a progressively distal spread from N1 to N3. | Count of Participants | Participants |
|
| Location | Location of primary tumor in the rectum. | Count of Participants | Participants |
|
| Histology | Type of tumor cell composition found by histopathology analysis. | Count of Participants | Participants |
|
| Mesorectal Fascia (FMR) | Distance from tumor to mesorectal fascia grouped in two categories depending on the distances: close (distance <=1 mm) or distal (NR). | Count of Participants | Participants |
|
| EMVI score | Extramural vascular invasion (EMVI) is the direct invasion of a blood vessel (usually a vein) by a tumor. In rectal cancer, this can occur on a macroscopic level and be detected on staging MRI. It is a significant prognostic factor, being a predictor of haematogenous spread. Score range from 0 to 4. Higher score means higher risk of distant metastasis. | Count of Participants | Participants |
|
| OG001 | 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 |
|
|
| 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. | Posted | Count of Participants | Participants | From baseline until 2 years and 2 months |
|
|
|
| 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. | Posted | Count of Participants | Participants | From baseline until 2 years and 2 months |
|
|
|
| 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). | Posted | Count of Participants | Participants | From baseline until 2 years and 2 months |
|
|
|
| Secondary | Number of Patients Reporting Surgical Complications | Surgical complications will be assessed by means of AEs reported during 30 days post surgery. | Posted | Count of Participants | Participants | From surgical intervention up to 30 days post-surgery, within a general time frame of 2 years and 2 months per study protocol |
|
|
|
| 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. | Posted | Number | 95% Confidence Interval | percentage of participants | At 3 years after study treatment completion, within a general time frame of 5 years and two months |
|
|
|
| 12 |
| 115 |
| 45 |
| 115 |
| 115 |
| 115 |
| EG001 | 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 | 7 | 65 | 16 | 65 | 65 | 65 |
| Peripheral neuropathy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Mucosal inflamation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysphonia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rectal hemorrage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Stomatitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Peripheral neuropathy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Mucosal inflamation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Decrease apetite | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysaesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysphonia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rectal hemorrage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysgeusia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| stomatitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Musculoesqueletal pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Epistaxis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| cystitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Aphonia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Upper abdominal pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Anal inflammation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rectal tenesmus | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | General disorders | MedDRA 20.1 | Systematic Assessment |
|
Not provided
Not provided
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006571 |
| Heterocyclic Compounds |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| mrT3 |
|
| mrT3B |
|
| mrT3A |
|
| mrT3C |
|
| mrT3D |
|
| mrT4 |
|
| mrT4A |
|
| mrT4B |
|
| Missing |
|
| Not available |
|
| TRG1-2 |
|
| CRM ≤ 1 |
|
| At least one Grade 3-4 AE |
|
| At least one AE that lead to treatment discontinuation |
|
| At least one AE that lead to death |
|
| At least one Serious Adverse Event (SAE) |
|
| At least one treatment-related AE |
|
| At least one treatment-related AE Grade 3-4 |
|
| At least one treatment-related AE that led to death |
|
| At least one treatment-related AE that led to permanent treatment discontinuation |
|
| At least one treatment-related Serious Adverse Event (SAE) |
|
| Postoperative AEs Grade 3-4 |
|
| Complications |
|
| Anastomosis fistula |
|
| wound infection |
|
| intraabdominal infection |
|
| Stoma complications |
|
| Reoperation |
|