Clinical Trial of Combination Chemotherapy With Aflibercept in Patients With Advanced Colorectal Cancer

NCT02129257 | Completed Phase 2

• 2 other identifiers: HE 6A/132013-002567-26
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 18

Brief Summary

The AMALTHEA (Aflibercept MAintenance after first-Line THErapy with FOLFIRI+Aflibercept in metastatic colorectal cancer patients) trial is an investigator-initiated, single arm, open-label, phase II study. Patients with histologically proven metastatic colorectal carcinoma will be treated with a combination of FOLFIRI and aflibercept for 6 months. Both Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type (wt) and mutant (mut) patients wil be enrolled. In the absence of Progressive Disease (PD) after 6 months of the combination of chemotherapy and aflibercept, the patient will be treated with a maintenance therapy with aflibercept alone until PD or unacceptable toxicity, investigator's decision or patient's refusal of further treatment or death, whichever comes first.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) rate at 1 year

  Up to 1 year

Secondary Outcomes (7)

• Evaluation of Objective Response Rate (ORR) defined as the proportion of patients with complete response (CR) or partial response (PR) among all patients, as assessed according to Response Evaluation Criteria for Solid Tumors (RECIST) v1.1

  Up to 20 months

• Evaluation of Overall Survival (OS)

  Time interval from registration to the date of death due to any cause assessed up to 60 months

• Evaluation of Progression-Free Survival (PFS)

  Time interval from registration to the first date of documented progression or death due to any cause assessed up to 60 months

• Number of participants with Serious and Non-Serious Adverse Events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0

  Up to 40 months

• Tumor tissue mRNA levels of VEGFA-121, VEGFA121b, VEGF-B, PlGF, VEGF-C, Semaphorins, HIF1, VEGFR1, VEGFR2, Neuropilins 1,2, Thrombospondin, Angiopoietins 1,2. Predictive significance for response rate, PFS, OS.

  Tumor blocks will be collected at baseline

Study Arms (1)

FOLFIRI-AFLIBERCEPT

EXPERIMENTAL

Aflibercept 4 mg/kg administered over 1 hour on Day 1, followed by FOLFIRI regimen. Treatment will be repeated every 2 weeks. FOLFIRI regimen: Irinotecan 180 mg/m² intravenous (IV) infusion and folinic acid 400 mg/m² IV infusion followed by: 5-fluorouracil (5-FU) 400 mg/m² IV bolus followed by: 5-FU 2400 mg/m² continuous IV infusion over 46 hours. FOLFIRI administration will immediately follow the aflibercept one. In the absence of PD after 6 months of the combination of chemotherapy and aflibercept, the patient will be treated with a maintenance therapy with aflibercept alone until PD or unacceptable toxicities, investigator's decision or patient's refusal of further treatment or death, whichever comes first.

Drug: AFLIBERCEPT; Drug: Irinotecan; Drug: 5-Fluorouracil; Drug: Folinic Acid

Interventions

AFLIBERCEPT DRUG

Also known as: Zaltrap, AVE005

FOLFIRI-AFLIBERCEPT

Irinotecan DRUG

Also known as: Campto

FOLFIRI-AFLIBERCEPT

5-Fluorouracil DRUG

FOLFIRI-AFLIBERCEPT

Folinic Acid DRUG

FOLFIRI-AFLIBERCEPT

Eligibility Criteria

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

You may qualify if:

• Histologically proven adenocarcinoma of the colon and/or rectum
• Metastatic disease confirmed clinically/radiologically
• Signed written informed consent
• No prior therapy for metastatic disease
• Duly documented inoperable metastatic disease, ie not suitable for complete curative surgical resection
• At least one measurable or evaluable lesion as assessed by Computed Tomography (CT) scan or MRI (Magnetic Resonance Imaging) according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2
• Adequate hematological status:
• neutrophils (ANC) ≥1.5x109/L
• platelets ≥100x109/L
• haemoglobin ≥9g/dL
• Adequate renal function: serum creatinine level \<1.5 mg/dl and Glomerular Filtration Rate\>50 ml/min by Cockroft/Gault formula
• Adequate liver function:
• serum bilirubin ≤1.5 x upper normal limit (ULN)

You may not qualify if:

• Exclusive presence of bone metastasis only
• Uncontrolled hypercalcemia
• Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg despite medical therapy), or history of hypertensive crisis, or hypertensive encephalopathy
• Concomitant 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 chronic disease
• History or presence of Central Nervous System (CNS) metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizures not controlled with standard medical therapy)
• Gilbert's syndrome
• Intolerance to atropine sulfate or loperamide
• Known dihydropyrimidine dehydrogenase deficiency
• Treatment with Cytochrome P450 3A4 (CYP3A4) inducers unless discontinued \> 7 days prior to randomization
• Other concomitant or previous malignancy, except:
• adequately treated in-situ carcinoma of the uterine cervix
• basal or squamous cell carcinoma of the skin
• cancer in complete remission for \>5 years

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead
• Sanofi: collaborator

Study Sites (18)

Agios Georgios Chania General Hospital

Chania, Mournies, 73300, Greece

Location

2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital

Athens, 11522, Greece

Location

251 Airforce Hospital

Athens, 11525, Greece

Location

2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio"

Athens, 11527, Greece

Location

Oncology Unit, 3rd Dept of Internal Medicine, Athens School of Medicine, Sotiria General Hospital

Athens, 11527, Greece

Location

Oncology Section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra"

Athens, 11528, Greece

Location

Division of Oncology, 2nd Dept of Internal Medicine, University Hospital "Attiko"

Athens, 12462, Greece

Location

2nd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, 14564, Greece

Location

3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, 14564, Greece

Location

3rd Dept of Medical Oncology, Hygeia Hospital

Athens, 15123, Greece

Location

1st Dept of Medical Oncology, Metropolitan Hospital

Athens, 18547, Greece

Location

2nd Dept of Medical Oncology, Metropolitan Hospital

Athens, 18547, Greece

Location

Dept of Medical Oncology, University Hospital of Heraklion

Heraklio, 71110, Greece

Location

Dept of Medical Oncology, Ioannina University Hospital

Ioannina, 45500, Greece

Location

Oncology Dept, University Hospital of Larissa

Larissa, 41334, Greece

Location

Division of Oncology, Dept of Internal Medicine, University Hospital of Patras

Pátrai, Greece

Location

Thermi Clinic S.A.

Thermi, 57001, Greece

Location

Dept of Medical Oncology, Papageorgiou General Hospital

Thessaloniki, 56429, Greece

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

aflibercept; Irinotecan; Fluorouracil; Leucovorin

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

Study Officials

• George Pentheroudakis, MD, Ass.Prof

  Dept of Medical Oncology, Ioannina University Hospital

  STUDY CHAIR

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: April 28, 2014
• First Posted: May 2, 2014
• Study Start: May 26, 2014
• Primary Completion: January 1, 2017
• Study Completion: September 25, 2017
• Last Updated: October 24, 2017

Record last verified: 2017-10

Locations

GR (18)