Trial in Metastatic Colorectal Cancer With FOLFIRI Plus Aflibercept as First Line Treatment

NCT02624726 | Unknown Phase 2

• 1 other identifier: CT/14.01
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 10

Brief Summary

Investigators propose to study the combination of m FOLFIRI plus Aflibercept in a Phase II trial of patients with metastatic colorectal cancer. The promising results of aflibercept derived from preclinical studies and from clinical trials conducted in patients with refractory of recurrent to oxaliplatin-based 1st line treatment in patients with mCRC open the field to explore such therapeutic approaches in the 1st line setting in combination with the FOLFIRI regimen.

Conditions

Metastatic Colorectal Cancer

Keywords

1st line; FOLFIRI; Aflibercept; mCRC

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Disease evaluation at Week 8

Secondary Outcomes (3)

• Progression Free Survival

  1 year

• Overall Survival

  1 year

• Toxicity profile (CTCAE v4.0)

  Every 2 weeks up to 100 weeks

Study Arms (1)

FOLFIRI/Aflibercept

EXPERIMENTAL

5 Fluorouracil/Leucovorin/Irinotecan/Aflibercept

Drug: 5 Fluorouracil; Drug: Leucovorin; Drug: Irinotecan; Drug: Aflibercept

Interventions

5 Fluorouracil DRUG

5 Fluorouracil: 400mg/m2, bolus infusion in \<5min followed by 5 Fluorouracil: 2400mg/m2, i.v in 46 hours continuous infusion (cycle repeated every two weeks)

Also known as: 5 Fluorouracil (5-FU)

FOLFIRI/Aflibercept

Leucovorin DRUG

Leucovorin: 400mg/m2, i.v in 2 hours infusion (cycle repeated every two weeks)

Also known as: Leucovorin (LV)

FOLFIRI/Aflibercept

Irinotecan DRUG

Irinotecan: 180mg/m2, i.v in 90min infusion (cycle repeated every two weeks)

Also known as: Irinotecan (CPT-11)

FOLFIRI/Aflibercept

Aflibercept DRUG

Aflibercept: 4mg/kg i.v in 1 hour infusion (cycle repeated every two weeks)

Also known as: Zaltrap

FOLFIRI/Aflibercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically documented adenocarcinomas of colon or rectum with unresectable metastatic disease.
• No prior treatment for metastatic disease
• Metastatic liver disease assessable with diffusion-weighted Magnetic Resonance Imaging (MRI)
• No previous treatment with bevacizumab or Cetuximab or Panitumumab.
• Patients may have receive fluoropyrimidines with or without oxaliplatin as adjuvant treatment, if they have progressed \> 12 months after the end of the last cycle of the adjuvant treatment
• Performance Status (ECOG) 0-2
• Life expectancy ≥ 3 months.
• Effective contraception for both male and female subjects if the risk of conception exists.
• Adequate laboratory parameters: Absolute neutrophils count ≥ 1.5 x 109 /L, Platelets ≥ 100 x 109 /L, Leucocytes \> 3,000/mm; Hemoglobin\> 10.5g/dl, creatinine clearance ≥ 60 ml/min, Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour, Magnesium ≥ lower limit of normal, Calcium ≥ lower limit of normal, total Bilirubin ≤ 1.5 times the upper limit of normal; aspartate and alanine aminotransferase ≤ 3 times of the upper normal limit in absence of liver metastases, or ≤5x Upper Normal Limits (UNL) in presence of liver metastases, alkaline phosphatases \< 5x UNL
• All patients will have to sign written informed consent in order to participate in the study.
• 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

You may not qualify if:

• Known hypersensitivity reaction to the component of the treatment.
• Inability to underwent a diffusion-weighted MR Imaging at baseline and in predefined time points
• Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
• History or evidence upon physical examination of Central Nervous System (CNS) metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
• 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
• Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
• Gilbert's syndrome
• Intolerance to atropine sulfate or loperamide
• Known dihydropyrimidine dehydrogenase deficiency
• Treatment with CYP3A4 inducers unless discontinued \> 7 days prior to randomization
• Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
• INR in absence of anticoagulation therapy \> 1.25 or poorly controlled anti-coagulation therapy on coumadin or heparin compounds (INR \>3.0)
• History of myocardial infarction and/or stroke within 6 months prior to randomization, New York Heart Association (NYHA) class III and IV congestive heart failure

Sponsors & Collaborators

• Hellenic Oncology Research Group: lead

Study Sites (10)

University Hospital of Heraklion Crete

Heraklion, Crete, 71110, Greece

Location

251 Air Forces Military Hospital of Athens

Athens, Greece

Location

Anicancer Hospital of Athens "Agios Savvas"

Athens, Greece

Location

Anticanscer Hospital of Athens "Agios Savvas"

Athens, Greece

Location

Athens Hospital "Mitera" Hygia Polis

Athens, Greece

Location

General Hospital of Athens "Aretaieio"

Athens, Greece

Location

General Hospital of Athens "Sotiria"

Athens, Greece

Location

IASO General Hospital

Athens, Greece

Location

University Hospital of Patras-Rio

Rio, Greece

Location

Thessaloniki Bioclinic

Thessaloniki, Greece

Location

Related Publications (1)

• Matikas A, Souglakos J, Katsaounis P, Kotsakis A, Kouroupakis P, Pantazopoulos N, Kentepozidis N, Nikolaidi A, Messaritakis I, Tzovara I, Hatzidaki D, Prinarakis E, Georgoulias V. MINOAS: A Single-arm Translational Phase II Trial of FOLFIRI Plus Aflibercept as First-line Therapy in Unresectable, Metastatic Colorectal Cancer. Target Oncol. 2019 Jun;14(3):285-293. doi: 10.1007/s11523-019-00647-3.

  PMID: 31203498 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Irinotecan; aflibercept

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)

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

Study Officials

• John Souglakos, MD

  Hellenic Oncology Research Group

  PRINCIPAL INVESTIGATOR

• Athanasios Kotsakis, MD

  Hellenic Oncology Research Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: December 8, 2015
• Study Start: January 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: March 1, 2019
• Last Updated: February 22, 2019

Record last verified: 2019-01

Locations

GR (10)