E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 evaluate the safety of aflibercept in patients with metastatic Colorectal Cancer (mCRC) treated with irinotecan/5FU combination (FOLFIRI) after failure of an oxaliplatin based regimen (patients similar to those evaluated in the VELOUR trial) |
|
E.2.2 | Secondary objectives of the trial |
To document the Health-Related Quality of Life (HRQL) of aflibercept in this patient population.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically or cytologically proven adenocarcinoma of the colon or rectum
Metastatic disease
Eastern Cooperative Oncology Group performance status 0-1
One and only one prior chemotherapeutic regimen for metastatic disease. This
prior chemotherapy must be an oxaliplatin containing regimen. Patients must
have progressed during or after the oxaliplatin based chemotherapy. Patients
relapsed within 6 months of completion of oxaliplatin adjuvant chemotherapy are
eligible. |
|
E.4 | Principal exclusion criteria |
Prior therapy with irinotecan
Inadequate bone marrow, liver and renal function: neutrophils < 1.5x109/L,
platelets < 100x109/L, hemoglobin < 9.0 g/dL, total bilirubin >1.5 x upper normal
limit (ULN), transaminases >3 x ULN (unless liver metastasis are present),
alkaline phosphatase >3 x ULN (unless liver metastasis are present), serum
creatinine > 1.5 x ULN.
Less than 4 weeks from prior radiotherapy, prior chemotherapy, prior major
surgery (or until the surgical wound is fully healed).
Treatment with any investigational drug within the prior 30 days.
Treatment with concomitant anticonvulsivant agents that are CYP3A4 inducers
(phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
History of brain metastases, uncontrolled spinal cord compression, or
carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
Prior malignancy (other than colorectal) including prior malignancy from which the
patient has been disease free for < 5 years (except adequately treated basal or
squamous cell skin cancer or carcinoma in situ of the cervix).
Any of the following within 6 months prior to study inclusion: myocardial infarction,
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe
congestive heart failure, stroke or transient ischemic attack.
Any of the following within 3 months prior study inclusion: severe gastrointestinal
bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive
oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis,
pulmonary embolism or other uncontrolled thromboembolic event.
Occurrence of deep vein thrombosis within 4 weeks, prior to study inclusion.
Known dihydropyrimidine dehydrogenase deficiency.
Predisposing colonic or small bowel disorders in which the symptoms were
uncontrolled.
Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea,
unresolved bowel obstruction/sub-obstruction, more than hemicolectomy,
extensive small intestine resection with chronic diarrhea.
Known Gilbert’s syndrome.
Unresolved or unstable toxicity from any prior anti cancer therapy at the time of
inclusion.
History of anaphylaxis or known intolerance to atropine sulphate or loperamide or
appropriate antiemetics to be administered in conjunction with FOLFIRI
(irinotecan, 5-Fluorouracil, leucovorin).
Severe acute or chronic medical condition, which could impair the ability of the
patient to participate to the study.
Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria
> 500 mg/24-h.
Uncontrolled hypertension within 3 months prior to study inclusion.
Patients on anticoagulant therapy with unstable dose of warfarin and/or having an
out-of-therapeutic range INR within the 4 weeks prior to study inclusion.
Evidence of clinically significant bleeding predisposition or underlying
coagulopathy, non-healing wound.
Pregnant or breast-feeding women.
Patients with reproductive potential who do not agree to use an accepted
effective method of contraception. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Number of participants reporting adverse events
- Number of participants reporting laboratory
abnormalities |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 30 days after the end of
treatment |
|
E.5.2 | Secondary end point(s) |
Health-Related Quality of Life (HRQL) assessed by
using changes from baseline in scores derived from
the 3 HRQL questionnaires |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 82 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Chile |
Colombia |
Denmark |
Finland |
Germany |
India |
Israel |
Italy |
Netherlands |
Norway |
Spain |
Sweden |
United Kingdom |
United States |
|
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
|
Patients included will continue to be treated until disease progression, death, unacceptable toxicity, Investigator’s decision or patient’s refusal of further treatment.
Follow-up period: patients will be followed up to 30 days after the last dose of study treatment (either aflibercept or FOLFIRI) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |