Two Chemotherapy Regimens Plus or Minus Bevacizumab (BETTER2)

May 7, 2024 updated by: Gustave Roussy, Cancer Campus, Grand Paris

Randomized Phase 2 Trial Of Two Chemotherapy Regimens Plus Or Minus Bevacizumab In Patients With Well Differentiated Pancreatic Neuroendocrine Tumors

Compare the effect of capecitabine (cape) + temozolomide (temo) and of 5FU + streptozotocin (strepto) given with a new schedule (LV5FU2 + strepto), two of the most used chemotherapy regimens in the treatment of well differentiated pancreatic neuroendocrine tumors alone or in combination with bevacizumab (beva) on progression-free survival (PFS) and compare the chemotherapy regimens alone or with beva (two by two design) on the same criteria.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Paris, France, 75015
        • Hopital Européen Georges Pompidou
      • Paris, France, 75012
        • Hopital Saint-Antoine
      • Paris, France, 75014
        • Hôpital Cochin
      • Paris, France, 75012
        • Hôpital Croix St Simon
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 06189
        • Centre Antoine Lacassagne
    • Calvados
      • Caen, Calvados, France, 14033
        • CHU de Caen
    • Côte d'Or
      • Dijon, Côte d'Or, France, 21000
        • CHU de Dijon
    • Gironde
      • Pessac, Gironde, France, 33600
        • Hôpital Haut-Lévêque
    • Haute-Garonne
      • Toulouse, Haute-Garonne, France, 31400
        • IUCT - Hôpital Rangueil
    • Hauts-de-Seine
      • Clichy, Hauts-de-Seine, France, 92110
        • Hopital Beaujon
    • Hérault
      • Montpellier, Hérault, France, 34298
        • Icm Val D'Aurelle
    • Indre-et-Loire
      • Chambray-lès-Tours, Indre-et-Loire, France, 37170
        • Hôpital Trousseau CHU Tours
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, France, 44800
        • Institut de Cancérologie de l'Ouest Site René Gauducheau
    • Loiret
      • Orléans, Loiret, France, 45067
        • CHR d'Orléans
    • Maine-et-Loire
      • Angers, Maine-et-Loire, France, 49100
        • Chu Angers
    • Marne
      • Reims, Marne, France, 51092
        • Hôpital Haut-Lévêque
    • Meurthe-et-Moselle
      • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54519
        • Institut de Cancerologie de Lorraine
    • Rhône
      • Lyon, Rhône, France, 69437
        • Hôpital Edouard Herriot
    • Val De Marne
      • Villejuif, Val De Marne, France, 94805
        • Gustave Roussy
    • Île-et-Vilaine
      • Rennes, Île-et-Vilaine, France, 35000
        • Centre Eugene Marquis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  1. Well differentiated pancreatic neuroendocrine tumor grade 1 (NET G1), grade 2 (NET G2) or grade 3 (NET G3)*

    *Grade 3 tumor must be confirmed by a pathologist of the TENpath network.

  2. Indication for chemotherapy for locally advanced or metastatic disease with proven progression (at least 20% increase of tumor size on a maximum of 12 months period of follow-up) or other indication of chemotherapy following the National Thesaurus of GI Cancerology (Appendix 6) (liver involvement > 50%, symptoms related to the tumour or its metastases, Ki67>10%)
  3. Patient with at least one measurable target tumor by RECIST 1.1 and that has never been irradiated
  4. Patient with a life expectancy greater than 3 months
  5. Men or women with performance status (ECOG) ≤ 2 (Appendix 3)
  6. Age ≥ 18 years
  7. Adequate hematological function: neutrophil count (ANC) ≥ 1.5x109/L, platelets greater than 75x109/L, hemoglobin greater than 10g/dl (blood transfusions are accepted to reach this level).
  8. Adequate liver function: serum bilirubin lower than 3 x upper limit of normal (ULN); aminotransferases and alkaline phosphatase levels lower than 2.5 ULN (lower than 5 ULN if liver metastases), TP greater than 50 %
  9. Proteinuria lower than 1g/24h, blood creatinine less than 120 μmol/L and creatinin clearance ≥ 60 ml/min as calculated by Cockroft-Gault formula Note: a negative dipstick urine analysis is sufficient.
  10. Absence of active bleeding, coagulopathy or pathologic condition that would confer a high risk of bleeding
  11. Prior treatment with somatostatin analogues, everolimus or sunitinib is allowed
  12. Negative serum pregnancy test ≤ 72 hours before randomization (for women of childbearing potential only). Sexually active women of childbearing potential must agree to use a highly effective method of contraception or to abstain from sexual activity during the study and for at least 6 months after the last study treatment administration. Sexually active males patients must agree to use condom during the study and for at least 6 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception.
  13. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
  14. Patient affiliated to a social security regimen or beneficiary of such regimen

Non inclusion criteria :

  1. Disease accessible to resection or percutaneous method of destruction
  2. Any known allergy or contraindication to the treatments used in the trial
  3. Patients with a complete DPD deficiency; defined as an uracil concentration ≥150ng/ml Note: patients with a suspicion of partial DPD deficiency, defined as a uracil concentration ≥ 16 ng/ml and < 150 ng/ml, will receive an adapted 1st cycle dose, according to a clinic-biological discussion. The dose can be then readapted for the second cycle according to the tolerability of the treatment during the 1st cycle.
  4. Patient previously treated with chemotherapy for the neuroendocrine tumour
  5. Patient have received any other antitumor therapy: chemotherapy, immunotherapy
  6. Other serious diseases such as respiratory failure or congestive heart failure, angina pectoris not medically controlled; history of myocardial infarction within 6 months prior to study entry, uncontrolled hypertension and arrhythmias, concomitant severe infection or uncontrolled diabetes mellitus
  7. Subjects with a history of chronic or acute hepatitis C or B infection.
  8. Surgery during the 5 weeks preceding the randomization
  9. History of cancer (except basal cell skin or carcinoma in situ carcinoma of the cervix) within 5 years prior to entry into the trial. But patients with cancers that have been treated more than 5 years ago and are considered as cured are eligible.
  10. Neurological or psychiatric pathology that may interfere with adherence to treatment
  11. Patients have received yellow fever vaccine within 30 days prior to the first dose of trial treatment.
  12. Patient with pernicious anaemia and other megaloblastic anaemias secondary to the lack of Vitamin B12
  13. Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
  14. Hypersensitivity to study drugs or any of its excipients
  15. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
  16. Pregnant or breast feeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LV5FU2 + streptozotocin
Drug: LV5FU2
LV5FU2 (Folinic Acid D, L 400 mg/m² day 1, 5FU 400 mg/m² IV bolus, 5FU 2400 mg/m² 48 hours continuous infusion)
Drug: Streptozocin
streptozotocin 800 mg/m² day 1 every 14 days
Experimental: Capecitabine + temozolomide
Drug: Capecitabine
Capecitabine 750 mg/m² twice daily, days 1-14
Drug: Temozolomide
temozolomide 200 mg/m² once daily, days 10-14, every 28 days
Experimental: LV5FU2 + streptozotocin + Bevacizumab
Drug: LV5FU2
LV5FU2 (Folinic Acid D, L 400 mg/m² day 1, 5FU 400 mg/m² IV bolus, 5FU 2400 mg/m² 48 hours continuous infusion)
Drug: Streptozocin
streptozotocin 800 mg/m² day 1 every 14 days
Drug: Bevacizumab
bevacizumab 5 mg/kg every 14 days
Experimental: Capecitabine + temozolomide + Bevacizumab
Drug: Bevacizumab
bevacizumab 5 mg/kg every 14 days
Drug: Capecitabine
Capecitabine 750 mg/m² twice daily, days 1-14
Drug: Temozolomide
temozolomide 200 mg/m² once daily, days 10-14, every 28 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Progression Free Survival (PFS) rate
Time Frame: Until disease progression or unacceptable toxicity (median 24 months)
Until disease progression or unacceptable toxicity (median 24 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Toxicity (NCI-CTCAE 4.0)
Time Frame: Until disease progression or unacceptable toxicity
Until disease progression or unacceptable toxicity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gustave Roussy, Cancer Campus, Grand Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 26, 2018

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 22, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017-000741-46
  • 2017/2523 (Other Identifier: CSET number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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