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Study 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 mCRC After Failure of an Oxaliplatin-based Regimen (AFEMA)

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ClinicalTrials.gov Identifier: NCT03279289
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : March 10, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Aflibercept Drug: Irinotecan Drug: folinic acid (dl racemic) Drug: 5Fluorouracil Drug: 5-FU Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomised, Multicentre, Phase II Pilot Study 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
Actual Study Start Date : October 25, 2017
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A
INDUCTION PHASE: 6 cycles of FOLFIRI + aflibercept MAINTENANCE PHASE: 5FU/LV + aflibercept
Drug: Aflibercept
4 mg/kg administered intravenous infusion on day 1

Drug: Irinotecan
180 mg/m2 intravenous infusion

Drug: folinic acid (dl racemic)
400 mg/m2 intravenous infusion

Drug: 5Fluorouracil
400 mg/m2 intravenous bolus

Drug: 5-FU
2400 mg/m2 continuous intravenous infusion over 46 hours

Active Comparator: Group B
FOLFIRI + aflibercept
Drug: Aflibercept
4 mg/kg administered intravenous infusion on day 1

Drug: Irinotecan
180 mg/m2 intravenous infusion

Drug: folinic acid (dl racemic)
400 mg/m2 intravenous infusion

Drug: 5Fluorouracil
400 mg/m2 intravenous bolus

Drug: 5-FU
2400 mg/m2 continuous intravenous infusion over 46 hours




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 48 months ]

Secondary Outcome Measures :
  1. Objective response rate based on the RECIST criteria [ Time Frame: 48 months ]
  2. Disease control rate [ Time Frame: 48 months ]
  3. Depth of response [ Time Frame: 48 months ]
  4. Time to progression [ Time Frame: 48 months ]
  5. Time to treatment failure [ Time Frame: 48 months ]
  6. Overall survival [ Time Frame: 48 months ]
  7. Incidence and severity of AEs CTCAE v4.03 criteria [ Time Frame: 48 months ]
  8. Incidence of dose adjustments and compliance [ Time Frame: 48 months ]
  9. VES-13 score (Vulnerable Elders Survey) as the utility measure for health deterioration [ Time Frame: 48 months ]

Other Outcome Measures:
  1. 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 [ Time Frame: 48 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
  2. Histologically proven adenocarcinoma of the colon and/or rectum,
  3. Existence of at least one measurable unidimensional lesion using CT or MRI based on the RECIST criteria, version 1.1
  4. Patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after a first line oxaliplatin-containing regimen for metastatic disease.
  5. Age ≥70 years
  6. World Health Organization (WHO) Performance status (PS) 0-2,
  7. Hematological status: neutrophils (ANC) ≥1.5x109 /L; platelets ≥100x109 /L; haemoglobin ≥9 g/dL
  8. Adequate renal function: Creatinine clearance ≥50 mL/min as calculated using the Cockcroft-Gault equation.
  9. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase (ALP) <5xULN
  10. Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour.
  11. Regular follow-up feasible.
  12. Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.

Exclusion Criteria:

  1. Uncontrolled hypercalcemia,
  2. Pre-existing permanent neuropathy (NCI grade >2)
  3. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy,
  4. Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
  5. Treatment with any other investigational medicinal product within 28 days prior to study entry.
  6. Other serious and uncontrolled non-malignant disease,
  7. 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),
  8. Patients classified as fragile or delicate according to the following criteria:

    1. Dependence in one or more activities of daily living according to the Katz Index of Independence in Activities of Daily Living (ADL) scale
    2. Three or more comorbidities when assessing the presence of the following processes: congestive heart failure; heart valve disease; coronary artery disease; chronic (obstructive or restrictive) pulmonary disease; cerebrovascular disease; peripheral neuropathy, chronic kidney failure; hypertension; diabetes; concomitant cancers; collagen vascular disease; chronic liver disease; and disabling arthritis
    3. Presence of geriatric syndromes: moderate-severe dementia; delirium in stressful situations (urinary or respiratory tract infection, angina or drugs); moderate-severe depression that interferes with the patient's usual activity; frequent falls (three or more per month); inattentiveness (who could help you in the event of an emergency?); urinary incontinence in the absence of stress, infection, diuretics or prostatic hyperplasia; faecal incontinence in the absence of diarrhoea or laxatives; osteoporotic fractures of large bones or vertebral compression fractures
  9. Known Gilbert's syndrome
  10. Intolerance to atropine sulfate or loperamide
  11. Known dihydropyrimidine dehydrogenase deficiency
  12. Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion
  13. 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.
  14. 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,
  15. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
  16. Patients with known allergy to any excipient to study drugs,
  17. History of myocardial infarction and/or stroke within 6 months prior to inclusion, NYHA class III and IV congestive heart failure
  18. Bowel obstruction.
  19. Less than 28 days elapsed from prior radiotherapy
  20. Patients with pernicious anemia or other megaloblastic anemias due to vitamin B12 deficiency
  21. Patients with severe infections

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03279289


Contacts
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Contact: Inmaculada Ruiz de Mena, PhD +34 91 378 82 75 ttd@ttdgroup.org

Locations
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Spain
Spanish Cooperative Group for Digestive Tumour Therapy (TTD) Recruiting
Madrid, Spain, 28046
Contact: Inmaculada Ruiz de Mena, PhD    0034 91 378 82 75    ttd@ttdgroup.org   
Sponsors and Collaborators
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Sanofi
Investigators
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Study Chair: Pilar García Alfonso Hospital Universitario Gregorio Marañón
Study Chair: Javier Sastre Valera Hospital Universitario Clínico San Carlos
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Responsible Party: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
ClinicalTrials.gov Identifier: NCT03279289    
Other Study ID Numbers: TTD-16-03
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD):
FOLFIRI
aflibercept
5-FU
oxaliplatin
elderly
metastatic colorectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Folic Acid
Fluorouracil
Irinotecan
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins