Study to Identify Biomarkers of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer
NCT ID: NCT02045030
Last Updated: 2016-11-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE2
14 participants
INTERVENTIONAL
2014-01-31
2016-11-30
Brief Summary
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An exploratory pharmacoeconomic analysis will be performed to evaluate productivity loss, quality of life and resource utilization while on treatment with aflibercept.
Detailed Description
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Biopsies and blood samples will be collected from all study patients. An exploratory pharmacoeconomic analysis will be performed to evaluate productivity loss, quality of life and resource utilization while on treatment with aflibercept.
A total of 52 patients will be enrolled, primarily at centers participating in the Q-CROC-01 study. The trial will close enrolment when 42 evaluable pre-treatment tumor biopsy samples have been obtained. Accrual of the total patient population is estimated to take 24-36 months with the estimated start date being February 2014.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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aflibercept and FOLFIRI
aflibercept and FOLFIRI
aflibercept + FOLFIRI
Aflibercept (Sanofi and Regeneron) targets the Vascular endothelial growth factor (VEGF) pathway that is a composite decoy receptor based on VEGFR-1 and VEGFR-2 fused to an Fc segment of IgG1. In pre-clinical assessments, aflibercept results in stronger angiogenesis inhibition than bevacizumab, exhibiting at least 100-1000 times higher affinity to the circulating VEGFs. It is postulated that in vivo, the binding of these ligands to aflibercept results in the blockade of tumor angiogenesis along with pruning of existing tumor vascular elements and reduction of VEGF-driven vascular permeability. The expected outcome is reduced growth of primary and metastatic tumors by impeding the density of tumor vasculature and diminishing the abnormal leakiness of tumor vessels that supply matrix components to the cancer.
Interventions
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aflibercept + FOLFIRI
Aflibercept (Sanofi and Regeneron) targets the Vascular endothelial growth factor (VEGF) pathway that is a composite decoy receptor based on VEGFR-1 and VEGFR-2 fused to an Fc segment of IgG1. In pre-clinical assessments, aflibercept results in stronger angiogenesis inhibition than bevacizumab, exhibiting at least 100-1000 times higher affinity to the circulating VEGFs. It is postulated that in vivo, the binding of these ligands to aflibercept results in the blockade of tumor angiogenesis along with pruning of existing tumor vascular elements and reduction of VEGF-driven vascular permeability. The expected outcome is reduced growth of primary and metastatic tumors by impeding the density of tumor vasculature and diminishing the abnormal leakiness of tumor vessels that supply matrix components to the cancer.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Patients must have received only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy must be an oxaliplatin containing regimen (in combination with bevacizumab). Patients who did not receive bevacizumab in their first-line treatment regimen may also be considered.
3. Metastatic disease that is not amenable to potentially curative treatment.
4. Measurable metastatic disease and evaluable disease.
5. ECOG 0 or 1.
6. Normal coagulation profile (PT, PTT, INR).
7. Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
8. Age ≥ 18 years.
Exclusion Criteria
2. Relapse from adjuvant treatment within 6 month of completion of adjuvant chemotherapy.
3. Less than 42 days elapsed from prior major surgery to the time of registration.
4. Inadequate or unusable tissue as the only tissue available for biopsy.
5. Any of the following within 3 months of registration: Grade 3-4 gastrointestinal bleeding/hemorrhage, diverticulitis, pulmonary embolism, inflammatory or infections bowel disease, treatment resistant peptic ulcer disease, colitis, erosive esophagitis or gastritis, uncontrolled thromboembolic event.
6. Prior intolerance to bevacizumab due to toxicity.
7. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
8. Gilbert's Syndrome.
9. Occurrence of deep vein thrombosis within 4 weeks, prior to registration.
10. Any of the following within 6 months prior to registration; myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
11. Contraindication to any of the components of the FOLFIRI chemotherapy regimen, as per investigators' judgement.
12. Inadequate bone marrow function as follows:
* Absolute neutrophil count (ANC) \< 1.5x 109/L
* Platelet count \< 100 x 109/L
* Hemoglobin \< 90 g/L
13. Inadequate liver function test:
* Total bilirubin \> 1.5 x ULN
* Transaminases \> 3 x ULN (if liver metastasis are present, 5 x ULN)
* Alkaline phosphatase \> 3 x ULN (if liver metastases are present, 5 x ULN)
14. Contraindication to aflibercept. Including:
* Urine protein-creatinine ratio (UPCR) \> 1 on morning spot urinalysis or proteinuria \>500 mg/24-h
* Serum creatinine \> 1.5 x upper limit of normal (ULN). If creatinine 1.0 - 1.5 x ULN, creatinine clearance, calculated according to Cockroft-Gault formula, \< 60 ml/min will exclude the patient.
* History of uncontrolled hypertension, defined as blood pressure \> 150/100 mgHG (grade ≥ 2 according to NCIC CTCAE v. 4.0), or systolic blood pressure \> 180 mmHG when diastolic blood pressure \< 90 mmHG, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment.
* Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-or-therapeutic range INR (\>3) within the 4 weeks prior to study entry.
* Evidence of clinically significant bleeding diathesis or underlying coagulopathy (eg. INR\>1.5 without vitamin K antagonist therapy), non-healing wound.
15. Known active brain metastases or meningeal disease.
16. Female patients who are pregnant or breastfeeding.
17. Patients of reproductive potential (male and female) who do not agree to use an accepted form of contraception during the study period and up to 6 months following completion of study treatment.
18. Concurrent treatment with other anti-cancer therapy (palliative radiation is allowed but patients must have a metastatic site available for biopsy that has not been irradiated).
19. Known infection with HIV.
18 Years
ALL
No
Sponsors
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Sanofi
INDUSTRY
Regeneron Pharmaceuticals
INDUSTRY
Quebec Clinical Research Organization in Cancer
OTHER
CR-CSSS Champlain-Charles-Le Moyne
OTHER
Responsible Party
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Principal Investigators
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Benoit Samson, MD
Role: PRINCIPAL_INVESTIGATOR
CSSS Champlain-Charles-Le Moyne
Locations
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CSSS Champlain-Charles-Le Moyne
Greenfield Park, Quebec, Canada
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Hôpital du Sacré-Coeur de Montréal
Montreal, Quebec, Canada
Countries
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References
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Wang TF, Lockhart AC. Aflibercept in the treatment of metastatic colorectal cancer. Clin Med Insights Oncol. 2012;6:19-30. doi: 10.4137/CMO.S7432. Epub 2012 Jan 4.
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.
Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, Ruff P, van Hazel GA, Moiseyenko V, Ferry D, McKendrick J, Polikoff J, Tellier A, Castan R, Allegra C. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012 Oct 1;30(28):3499-506. doi: 10.1200/JCO.2012.42.8201. Epub 2012 Sep 4.
Other Identifiers
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Q-CROC-04
Identifier Type: -
Identifier Source: org_study_id