Aflibercept and Chemotherapy as First Line Treatment for Metastatic Colorectal Cancer Assessable With DCE-US (PULSAR).

NCT02173990 | Terminated Phase 2 DMC

• 2 other identifiers: PULSAR-13032013-004540-33
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

Brief Summary

The PULSAR trial is an international, investigator-initiated, single arm open-label phase II study. The aim of this study is to measure the clinical activity of the combination FOLFIRI-aflibercept in an homogeneous group of patients with metastatic colorectal cancer, and treated with a FOLFIRI-aflibercept regimen as first line treatment.

Conditions

Metastatic Colorectal Cancer

Keywords

adenocarcinoma; colon and/or rectum

Outcome Measures

Primary Outcomes (1)

• Progression-Free Rate will be assessed according to RECIST 1.1 with central radiological review.

  At 10-month

Secondary Outcomes (7)

• Overall Response Rate (ORR) will be determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  through the end of study treatment, an average of 1 year

• Best Response Rate (BRR)

  through the end of study treatment, an average of 1 year

• Progression-free survival (PFS)

  through study completion, an average of 3 years

• Progression-free survival rate

  through study completion, an average of 3 years

• Patterns of PFS according to DCE-US early assessment

  at day 28 ± 2

Study Arms (1)

Aflibercept-FOLFIRI

EXPERIMENTAL

On day 1 of each cycle patients will receive aflibercept followed by irinotecan, 5-FU and leucovorin (FOLFIRI regimen). This treatment will be repeated every 2 weeks until RECIST progression or intolerance.

Drug: Aflibercept-FOLFIRI

Interventions

Aflibercept-FOLFIRI DRUG

Aflibercept : 4 mg/kg, IV over 1 h on Day 1 FOLFIRI : * Irinotecan 180 mg/m² IV infusion in 500 mL D5W (5% Dextrose in Water solution) over 90 minutes and dl leucovorin\* 400 mg/m² IV infusion over 2 hours, at the same time, in bags using a Y-line, followed by : * 5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by : * 5-FU 2400 mg/m² continuous IV infusion in 500 mL over 46-hours. * \*400 mg/m² of leucovorin expressed in dl racemic. When the l-isomer form is used the dose should be divided by 2, i.e. 200 mg/m²

Also known as: ZALTRAP-FOLFIRI

Aflibercept-FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), 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
• Metastatic disease confirmed clinically/radiologically, and evaluable by dynamic contrast ultrasound
• No prior therapy for metastatic disease
• Duly documented inoperable metastatic disease, i.e. not suitable for complete curative surgical resection
• At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2
• Adequate hematological status: neutrophils (ANC) ≥ 1.5 x109/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), alkaline phosphatase, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \< 5 x ULN
• Proteinuria \< 2+ (dipstick urinalysis) or ≤ 1g/24 hour
• Female patients must commit to using reliable and appropriate methods of contraception until at least 6 months after the end of Aflibercept and 3 months after the end of Irinotecan (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 until at least 6 months after the end of Aflibercept and 3 months after the end of Irinotecan.

You may not qualify if:

• Uncontrolled hypercalcemia
• Uncontrolled systemic 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
• Right-left shunt or severe pulmonary arterial hypertension (pulmonary artery pressure \> 90 mmHg)
• Respiratory distress syndrome
• Concomitant antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy)
• Treatment with any other investigational medicinal product within 28 days prior to study entry
• 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 registration
• Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \> 5 years,
• Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
• Pregnant or breastfeeding women
• Patients with known allergy to any excipients to study drugs (including hypersensitivity to sulphur hexafluoride or to any of the components of SonoVue)

Sponsors & Collaborators

• Centre Oscar Lambret: lead
• Sanofi: collaborator

Study Sites (8)

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Kremlin Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

CHRU

Lille, 59037, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Hôpital Universitaire Paul Brousse

Villejuif, 94804, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Adenocarcinoma

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; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Antoine ADENIS, MD, PhD

  Centre Oscar Lambret - France

  STUDY DIRECTOR

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: February 17, 2014
• First Posted: June 25, 2014
• Study Start: July 1, 2014
• Primary Completion: November 2, 2018
• Study Completion: October 22, 2019
• Last Updated: October 20, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)