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

NCT03279289 | Completed Phase 2

• 1 other identifier: TTD-16-03
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

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

Conditions

Metastatic Colorectal Cancer

Keywords

FOLFIRI; aflibercept; 5-FU; oxaliplatin; elderly; metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  48 months

Secondary Outcomes (9)

• Objective response rate based on the RECIST criteria

  48 months

• Disease control rate

  48 months

• Depth of response

  48 months

• Time to progression

  48 months

• Time to treatment failure

  48 months

Other Outcomes (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

  48 months

Study Arms (2)

Group A

EXPERIMENTAL

INDUCTION PHASE: 6 cycles of FOLFIRI + aflibercept MAINTENANCE PHASE: 5FU/LV + aflibercept

Drug: Aflibercept; Drug: Irinotecan; Drug: folinic acid (dl racemic); Drug: 5Fluorouracil; Drug: 5-FU

Group B

ACTIVE COMPARATOR

FOLFIRI + aflibercept

Drug: Aflibercept; Drug: Irinotecan; Drug: folinic acid (dl racemic); Drug: 5Fluorouracil; Drug: 5-FU

Interventions

Aflibercept DRUG

4 mg/kg administered intravenous infusion on day 1

Group A; Group B

Irinotecan DRUG

180 mg/m2 intravenous infusion

Group A; Group B

folinic acid (dl racemic) DRUG

400 mg/m2 intravenous infusion

Group A; Group B

5Fluorouracil DRUG

400 mg/m2 intravenous bolus

Group A; Group B

5-FU DRUG

2400 mg/m2 continuous intravenous infusion over 46 hours

Group A; Group B

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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:
• Dependence in one or more activities of daily living according to the Katz Index of Independence in Activities of Daily Living (ADL) scale
• 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
• 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
• Known Gilbert's syndrome
• Intolerance to atropine sulfate or loperamide
• Known dihydropyrimidine dehydrogenase deficiency
• 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,

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Sanofi: collaborator

Study Sites (1)

Spanish Cooperative Group for Digestive Tumour Therapy (TTD)

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

aflibercept; Irinotecan; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Pilar García Alfonso

  Hospital Universitario Gregorio Marañón

  STUDY CHAIR

• Javier Sastre Valera

  Hospital Universitario Clínico San Carlos

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: September 12, 2017
• Study Start: October 25, 2017
• Primary Completion: February 9, 2023
• Study Completion: February 9, 2023
• Last Updated: April 13, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)