BETTER 2: Two Chemotherapy Regimens Plus or Minus Bevacizumab
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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: Capecitabine
Capecitabine 750 mg/m² twice daily, days 1-14
Drug: Temozolomide
temozolomide 200 mg/m² once daily, days 10-14, every 28 days
Drug: Bevacizumab
bevacizumab 5 mg/kg every 14 days
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [Until disease progression or unacceptable toxicity (median 24 months)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Well differentiated pancreatic neuroendocrine tumor grade 1 (NET G1) or grade 2 (NET G2) or grade 3 (NET G3)
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Indication for chemotherapy for locally advanced or metastatic disease with proven progression (at least 20% increase of tumor size on a maximum 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%) (Appendix 6)
-
Patient with at least one measurable target tumor by RECIST 1.1 that thas never been irradiated
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Patient with a life expectancy greater than 3 months
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Men or women with performance status (ECOG) ≤ 2
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Age ≥ 18 years
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Adequate hematological function: neutrophil count (ANC) ≥ 1,5x109/L, platelets >/= 75x109/L, hemoglobin >/= 10g/dl (blood transfusions are accepted to reach this level).
-
Adequate liver function: serum bilirubin </= 3 x upper limit of normal (ULN); aminotransferases and alkaline phosphatase levels </= 2.5 ULN (</= 5 ULN if liver metastases), TP > 50%
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Proteinuria ≤ 1g/24 h, 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.
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Absence of active bleeding, coagulopathy or pathologic condition that would confer a high risk of bleeding
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Prior treatment with somatostatin analogues, everolimus or sunitinib is allowed
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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.
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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.
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Patient affiliated to a social security regimen or beneficiary of such regimen
Exclusion Criteria:
-
Disease accessible to resection or percutaneous method of destruction
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Any known allergy or contraindication to the treatments used in the trial, 2.1 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.
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Patient previously treated with chemotherapy for the neuroendocrine tumour
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Patient have received any other antitumor therapy: chemotherapy, immunotherapy
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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.
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Subjects with a history of chronic or acute hepatitis C or B infection.
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Surgery during the 5 weeks preceding the randomization
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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.
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Neurological or psychiatric pathology that may interfere with adherence to treatment
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Patients have received yellow fever vaccine within 30 days prior to the first dose of trial treatment.
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Patient with pernicious anaemia and other megaloblastic anaemias secondary to the lack of Vitamin B12
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Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
-
Hypersensitivity to study drugs or any of its excipients
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Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
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Pregnant or breast feeding women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gustave Roussy | Villejuif | Val De Marne | France | 94805 |
Sponsors and Collaborators
- Gustave Roussy, Cancer Campus, Grand Paris
- National Cancer Institute, France
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017-000741-46
- 2017/2523