Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms

NCT ID: NCT02970916

Last Updated: 2019-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2018-12-31

Brief Summary

The purpose of this study is to assess FOLFIRI+aflibercept efficacy in patients with or without ACE polymorphisms in terms of Progression-free survival (PFS).

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFIRI+aflibercept

Group Type: EXPERIMENTAL

FOLFIRI+aflibercept

Intervention Type: DRUG

Aflibercept: 4 mg/kg administered intravenous infusion on day 1

FOLFIRI regimen immediately after aflibercept:

Irinotecan:180 mg/m2 intravenous infusion, folinic acid (dl racemic): 400 mg/m2 intravenous infusion, followed by 5-fluorouracil (5-FU): 400 mg/m2 intravenous bolus, followed by 5-FU: 2400 mg/m2 continuous intravenous infusion over 46 hours.

• folinic acid: 400 mg/m² (racémic) or 200 mg/m² (L-form)

Interventions

FOLFIRI+aflibercept

Aflibercept: 4 mg/kg administered intravenous infusion on day 1

FOLFIRI regimen immediately after aflibercept:

Irinotecan:180 mg/m2 intravenous infusion, folinic acid (dl racemic): 400 mg/m2 intravenous infusion, followed by 5-fluorouracil (5-FU): 400 mg/m2 intravenous bolus, followed by 5-FU: 2400 mg/m2 continuous intravenous infusion over 46 hours.

• folinic acid: 400 mg/m² (racémic) or 200 mg/m² (L-form)

Intervention Type: DRUG

Eligibility 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. Metastatic disease confirmed.

4. Existence of at least one measurable unidimensional lesion using CT or MRI based on the RECIST criteria, version 1.1

5. Patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after an oxaliplatin-containing regimen.

6. Age ≥18 years

7. World Health Organization (WHO) Performance status (PS) 0-2,

8. Hematological status: neutrophils (ANC) ≥1.5x109 /L; platelets ≥100x109 /L; haemoglobin ≥9g/dL

9. Adequate renal function: serum creatinine level < 1.5 x ULN

10. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase (ALP) <5xULN

11. Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour.

12. Regular follow-up feasible.

13. For female patients of childbearing potential, negative serum pregnancy test

14. Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). 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 ncephalopathy,

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. Known Gilbert's syndrome

9. Intolerance to atropine sulfate or loperamide

10. Known dihydropyrimidine dehydrogenase deficiency

11. Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion

12. 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.

13. 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,

14. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days

15. Pregnant or breastfeeding women,

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enrique Aranda, MD-PhD

Role: STUDY_CHAIR

Hospital Universitario Reina Sofía

Auxiliadora Gómez, MD-PhD

Role: STUDY_CHAIR

Hospital Universitario Reina Sofía

Locations

Spanish Cooperative Group for the Treatment of Digestive Tumors

Madrona, , Spain

Countries

Spain

Other Identifiers

TTD-16-02

Identifier Type: -

Identifier Source: org_study_id