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| Name | Class |
|---|---|
| Sanofi | INDUSTRY |
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The purpose of this study is to assess the efficacy and safety of treatment with FOLFIRI-aflibercept compared to initial treatment with FOLFIRI-aflibercept (for 6 cycles) followed by maintenance with 5FU-aflibercept, in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | INDUCTION PHASE: 6 cycles of FOLFIRI + aflibercept MAINTENANCE PHASE: 5FU/LV + aflibercept |
|
| Group B | Active Comparator | FOLFIRI + aflibercept |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aflibercept | Drug | 4 mg/kg administered intravenous infusion on day 1 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival | 48 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate based on the RECIST criteria | 48 months | |
| Disease control rate | 48 months | |
| Depth of response |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarkers in serum and tumour tissue associated with cell and tumour growth and/or involved in the mechanism of action of FOLFIRI+aflibercept and their correlation with efficacy parameters | 48 months |
Inclusion Criteria:
Exclusion Criteria:
Uncontrolled hypercalcemia,
Pre-existing permanent neuropathy (NCI grade >2)
Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy,
Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
Treatment with any other investigational medicinal product within 28 days prior to study entry.
Other serious and uncontrolled non-malignant disease,
History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
Patients classified as fragile or delicate according to the following criteria:
Known Gilbert's syndrome
Intolerance to atropine sulfate or loperamide
Known dihydropyrimidine dehydrogenase deficiency
Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion
Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis.
Other concomitant or previous malignancy, except: i/ adequately treated insitu carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
Patients with known allergy to any excipient to study drugs,
History of myocardial infarction and/or stroke within 6 months prior to inclusion, NYHA class III and IV congestive heart failure
Bowel obstruction.
Less than 28 days elapsed from prior radiotherapy
Patients with pernicious anemia or other megaloblastic anemias due to vitamin B12 deficiency
Patients with severe infections
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| Name | Affiliation | Role |
|---|---|---|
| Pilar GarcÃa Alfonso | Hospital Universitario Gregorio Marañón | Study Chair |
| Javier Sastre Valera | Hospital Universitario ClÃnico San Carlos | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spanish Cooperative Group for Digestive Tumour Therapy (TTD) | Madrid | 28046 | Spain |
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| Irinotecan |
| Drug |
180 mg/m2 intravenous infusion |
|
| folinic acid (dl racemic) | Drug | 400 mg/m2 intravenous infusion |
|
| 5Fluorouracil | Drug | 400 mg/m2 intravenous bolus |
|
| 5-FU | Drug | 2400 mg/m2 continuous intravenous infusion over 46 hours |
|
| 48 months |
| Time to progression | 48 months |
| Time to treatment failure | 48 months |
| Overall survival | 48 months |
| Incidence and severity of AEs CTCAE v4.03 criteria | 48 months |
| Incidence of dose adjustments and compliance | 48 months |
| VES-13 score (Vulnerable Elders Survey) as the utility measure for health deterioration | 48 months |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| C533178 | aflibercept |
| D000077146 | Irinotecan |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| 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 |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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