E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic unresectable colorectal cancer (mCRC) . |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To assess Pogression Free Survival (PFS) of treatment |
|
E.2.2 | Secondary objectives of the trial |
- To assess OS
- To evaluate Response Rate (RR) (RECIST version 1.1)
- To evaluate Duration of Response (DOR)
- To evaluate Time to Progression (TTP)
- To evaluate Time to Response (TTR)
- To evaluate Resection Rate?
- To evaluate the Safety profile of both combinations
- To study the relationship between the levels of proangiogenic cytokines / biomarkers and
outcome, PFS, OS.
- Health economic evaluation -To evaluate Quality of Life |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MOLECULAR PROFILE SUB-ANALYSIS
date: 20.FEB.2014
Version 2014.02
Research objectives of the sub-analysis:
The aims addressed in this research project are those related to a better, individualized treatment prediction and real-time follow-up, using non-invasive “liquid biopsy” in mCRC patients treated with anti-EGFR therapy. The primary endpoint is the percentage of patients where acquired resistance could be predicted due to a novel RAS family mutation detected in the “real-time biopsy”. We consider that, if such a change in mutational status occurs in either first, second or third line regimens, in up to 10% of patients, our approach would deserve implementation on a routine scale.
The specific objects of this research are:
Prospectively: to validate the importance of RAS mutations and 4 additional emerging biomarkers, for prediction of acquired resistance to EGFR inhibition in a multicenter prospective study using “real-time biopsy”.
Translationally: to formulate recommendations for future interventional validation studies or implementation of our non-invasive biopsy approach in the clinic. |
|
E.3 | Principal inclusion criteria |
- Patients with histological confirmed diagnosis of metastatic CRC
- Confirmed Ras WT status by central laboratory in UZA
- At least one measurable lesion according to RECIST version 1.1
- Evaluation of tumor disease according to RECIST by investigator, 4 weeks or less prior inclusion.
- No major surgery within 4 weeks prior to inclusion
- Wound healing completed
- Age ≥18 years
- Life expectancy > 3 months
- ECOG ≤ 2
- Neutrophils ≥ 1.500/μl
- Platelets ≥ 100.000μl
- Hemoglobin > 9 g/dl
- Creatinine clearance > 30 ml/min, serum creatinine < 1.25 x upper normal limit
- Serum bilirubin < 1.25x upper normal limit, AST / ALT < 2.5 x ULN
- In case of liver metastasis, serum bilirubin < 1.5 x upper normal limit, AST/ALT < 5 x ULN
- Signed written informed consent
- Fertile women (< 2 years after last menstruation) and men of childbearing potential must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) |
|
E.4 | Principal exclusion criteria |
- Current and/or previous treatment with any other investigational agent or other biological agent (e.g. cetuximab).
- Participation in another clinical trial within 30 days prior to entering this study
Other conditions
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- NYHA Class II or greater CHF
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- Known CNS disease, except for treated brain metastasis (treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement fo dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radio surgery (RS; Gamma Knife; LINAC; or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months of start of study therapy will be excluded).
- Significant vascular disease (e.g. aortic aneurysm requiring surgical intervention, pulmonary embolism or recent peripheral arterial thrombosis) within 6 months prior start of study treatment.
- History of haemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to start of study treatment
- Evidence of bleeding diathesis or significant coagulopathy (in absence of therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to start of study therapy, or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior start of study therapy.
- History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline CT scan.
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study therapy.
- Serious, non healing wound, active ulcer, or untreated bone fracture
- History or evidence upon physical/neurological
- Known hypersensitivity to any of the study drugs
- Acute intra abdominal inflammatory process
- Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications
- Patients with contraindication for oxaliplatin containing chemotherapy (e.g. patients with serious polyneuropathy > grade 1)
- Previous radiotherapy: Patients must have recovered from any radiotherapy toxicity prior to enrolment
- Life expectancy less than 3 months
- Inability or unwillingness to comply with the protocol |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) rate at 1 years after randomisation |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 years after randomisation |
|
E.5.2 | Secondary end point(s) |
- To evaluate Response Rate (RR) (RECIST version 1.1)
- To evaluate Resection Rate?
- To evaluate the Safety profile of both combinations
- To asses Overall Survival |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
after end of chemotherapy (3 month) in both arms
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Panitumumab versus Bevacizumab in combination with oxaliplatin – 5 FU (FOLFOX) |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last follow up visit of the last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |