Primary: To provide metastatic colorectal cancer patients with access to aflibercept and todocument the overall safety in these patientsSecondary: To document the Health-Related Quality of Life of aflibercept in this patientpopulation
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Number of patients reporting adverse events up to 30 days after the end of
treatment.
- Number of patients reporting laboratory abnormalities up to 30 days after the
end of treatment.
Secondary outcome
Health-Related Quality of Life (HRQL) assessed by using changes from baseline
in scores derived from the 3 HRQL questionnaires (EQ-5D, EORTC QLQ-C30 and
EORTC QLQ-CR-29), every 4 weeks.
Background summary
Aflibercept is a man-made novel anti-cancer agent of the antiangiogenic class
(i.e. that causes decreased blood vessel formation). This is a protein and,
like agents of the same category, has a different mechanism of action than the
chemotherapy that will be given with it. Therefore, when added to the
chemotherapy, it is hypothesised that it might expand the benefit of the
chemotherapy itself.
So far more than 3700 patients have received aflibercept alone or in
combination with different chemotherapies including irinotecan and 5-FU/LV, in
several clinical studies.
In the phase III/IV trial conducted in metastatic colorectal cancer patients,
previously treated with an oxaliplatin containing chemotherapy, the combination
of aflibercept (AVE0005) with irinotecan, 5-fluorouracil and leucovorin
(FOLFIRI) has demonstrated a statistically significant and clinically
meaningful improvement in patient survival and delaying the progression of the
disease. Overall, the side effects noted when aflibercept and FOLFIRI were
combined, were more frequent than ones observed with FOLFIRI alone however, the
toxicities observed were consistent with the type of side effects observed with
the chemotherapy and with agents belonging to the same class as aflibercept
(antiangiogenic compounds).
This study aims to provide access for patients to aflibercept (given in
combination with FOLFIRI) and will permit gathering information about its
safety and tolerability and about the quality of life while treated.
Study objective
Primary: To provide metastatic colorectal cancer patients with access to
aflibercept and to
document the overall safety in these patients
Secondary: To document the Health-Related Quality of Life of aflibercept in
this patient
population
Study design
This is a prospective, phase IIIb/IV, International, Multicenter, Single Arm,
Open-label Study.
Each patient will be treated until disease progression, unacceptable toxicity,
death, Investigator*s decision or
patient*s refusal for further treatment (whichever come first).
Patients will be followed-up during treatment and for at least 30 days after
last treatment (either aflibercept or FOLFIRI)
administration (for safety assessment).
Intervention
Aflibercept one (1) hour intravenous infusion every two (2) weeks in
combination with FOLFIRI (ironotecan, 5-Fluorouracil and leucovorin) regimen.
Study burden and risks
Risks are related to blood sampling and possible site effects of the study
drug.
Potential benefits include possible shrinkage of the patient's tumor, delaying
in progression of the disease and/or prolongation of the patient's overall
survival.
Kampenringweg 45
GOUDA 2803 PE
NL
Kampenringweg 45
GOUDA 2803 PE
NL
Listed location countries
Age
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.
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
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005724-17-NL |
| ClinicalTrials.gov | NCT01571284 |
| CCMO | NL40690.060.12 |