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Metastatic Colorectal CancerPhase 2PULSARNCT02173990

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

A Phase 2 study testing Aflibercept-FOLFIRI in people with Metastatic Colorectal Cancer, run by Centre Oscar Lambret at 8 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Aflibercept-FOLFIRI
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
8 sitesFrance
Study dates
Jul 2014to 22 Oct 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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
  • 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 chronic inflammatory bowel disease, or diverticulitis
  • 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)
  • History of myocardial infarction and/or stroke or other arterial thrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration
  • Poorly controlled cardiac arrhythmias
  • Typical Angina Pectoris at rest within the previous 7 days, or significant worsening of cardiac symptoms in the previous 7 days, or recent intervention on the coronary arteries or other factors suggesting clinical instability (eg recent deterioration of ECG changes in clinical parameters or biological), or acute heart failure, or heart failure stage III or IV, or severe arrhythmias
  • Bowel obstruction
  • History of severe tumour bleeding or bleeding disorders
  • Poorly controlled anti-coagulation therapy (INR > 3.0 on coumadin or heparin compounds)
  • Palliative radiation therapy within 4 weeks prior to registration
  • St John's Wort medication

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

France8 sites

  • Institut Bergonié

    Bordeaux, 33076

  • Centre Georges François Leclerc

    Dijon, 21079

  • Kremlin Bicetre

    Le Kremlin-Bicêtre, 94275

  • Centre Oscar Lambret

    Lille, 59020

  • CHRU

    Lille, 59037

  • Institut Paoli Calmettes

    Marseille, 13273

  • Hôpital Universitaire Paul Brousse

    Villejuif, 94804

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: A Phase 2 Study of Aflibercept and Chemotherapy as First Line Treatment for Metastatic Colorectal Cancer Assessable With DCE-US.

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.

Read the detailed description

Patients with an unresectable metastatic colorectal carcinoma (mCRC) histologically proven will be treated with a combination of Irinotecan/bolus-infusion-5-Fluorouracil/Leucovorin (FOLFIRI regimen) and aflibercept. On day 1 of each cycle patients will receive aflibercept followed by irinotecan, 5-Fluorouracil (FU) and leucovorin (FOLFIRI regimen). This treatment will be repeated every 2 weeks until RECIST progression or unacceptable toxicities, investigator's decision or patient's refusal of further treatment or death, whichever comes first.

All patients will be assessed during their FOLFIRI-aflibercept with Dynamic Contrast Enhanced Ultrasound (DCE-US) at baseline, D7 (± 1 day), D28 (± 2 days).

The recruitment period is 24 months. The average duration of the study per patient will be approximately 12 months, i.e. 3 weeks for screening, 10 months for the combination of FOLFIRI plus aflibercept and 30 days for follow-up of adverse events after the last dose of study treatment.

Being tested
Aflibercept-FOLFIRI
Keywords
adenocarcinoma, colon and/or rectum
Medical subject headings
Colorectal Neoplasms, Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aflibercept-FOLFIRIDrug

    Also called ZALTRAP-FOLFIRI

    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
Study groups in NCT02173990
Study groupRoleWhat they receive
Aflibercept-FOLFIRIExperimentalOn 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.
Receives: Drug: Aflibercept-FOLFIRI

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: At 10-month

Secondary outcomes (7)

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

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

  2. Best Response Rate (BRR)

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

  3. Progression-free survival (PFS)

    Measured: through study completion, an average of 3 years

  4. Progression-free survival rate

    Measured: through study completion, an average of 3 years

  5. Patterns of PFS according to DCE-US early assessment

    Measured: at day 28 ± 2

  6. Pharmacodynamic activity

    Measured: at day 7 ± 1, and day 28 ± 2

  7. Safety and tolerance

    Measured: up to 30 days after the end of the study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2014 (estimated)
  2. Study startJul 2014
  3. Primary completion2 Nov 2018
  4. Study completion22 Oct 2019

Why it stopped: Lack of enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02173990
Sponsor's protocol ID
PULSAR-1303
Other IDs
2013-004540-33
Acronym
PULSAR
Status last verified
Oct 2021
First submitted
17 Feb 2014
Last updated
20 Oct 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aflibercept-FOLFIRI in people with Metastatic Colorectal Cancer, run by Centre Oscar Lambret at 8 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Rate will be assessed according to RECIST 1.1 with central radiological review. (time frame: At 10-month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02173990.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2021.

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