Pancreatic Neuroendocrine Tumors, Pancreatic Neuroendocrine Tumors (pNET)
Conditions
Keywords
R0 resected, stage I-III, CAPECITABINE, TEMOZOLOMIDE, active surveillance
Brief summary
ADJUPANET is an open label, double arm, multicenter, phase 3 trial that aims to investigate the efficacy of systemic chemotherapy in locally resected aggressive pancreatic neuroendocrine tumors. The two arms of patients are the following : i. control arm : active surveillance only, standard of care. ii. experimental arm : adjuvant chemotherapy with 6 cycles of CAPECITABINE-TEMOZOLOMIDE (per os) and active surveillance. Patients enrolled in the experimental arm will receive Capecitabine CAPECITABINE per os 750 mg/m² (twice a day: D1 to D14) D1=D28 and TEMOZOLOMIDE per os 200 mg/m² (once a day: D10 to D14) D1=D28.
Interventions
DRUGAdjuvant chemotherapy with Capecitabine-Temozolomide
Chemotherapy with Capecitabine-Temozolomide (per os) for 6 cycles (6 months): * CAPECITABINE per os 750 mg/m² (twice a day: D1 to D14) D1=D28 * TEMOZOLOMIDE per os 200 mg/m² (once a day: D10 to D14) D1=D28
OTHERActive surveillance
Active surveillance according to the European Society for Medical Oncology (ESMO) and French Thesaurus National de Cancérologie Digestive (TNCD) guidelines with every 3 months for 2 years, every 4 months for 1 year and then every 6 months for 2 years: * Evaluation and physical examination of a functional clinical syndrome (hormone- and tumor-related symptoms) * Biological: chromogranin A and/or appropriate hormone biomarker if positive in the preoperative setting * Radiological: thoracic CT and abdomen CT or MRI
Sponsors
Gustave Roussy, Cancer Campus, Grand Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologically proven well differentiated neuro-endocrine tumour of the pancreas by local teams 2. Availability of the primary tumor specimen, allowing accurate WHO classification and determination of MGMT status 3. Stage I-III based ENETS-UICC 8th classification 4. Early postoperative context (≤ 4 months) 5. R0 resection 6. Absence of distant metastasis or local tumor remnant as defined by a negative post-operative thorax CT and -abdomen CT or MRI and negative (best of DOTA-peptide 68Ga or, FDG) PET imaging if performed preoperatively 7. ECOG 0-1 8. No prior systemic therapy 9. Intermediate to high risk of recurrence as defined by the following situations: * Ki67 ≥ 10% (i.e.: Grade 3 or high Ki67 Grade 2) * Ki67 5-9% AND (tumor size \> 3 cm OR Node positive) * Ki67 3-5% AND tumor size \> 3 cm AND Node positive * Ki67 \< 3% AND tumor size \> 3 cm AND Node positive AND (Vascular Emboli OR perineural invasion) 10. Age ≥ 18 years at the time of consent, no superior limit 11. Adequate bone marrow reserve (hemoglobine \> 8 g/dL, absolute neutrophils count ≥ 1500/mm³ and platelets ≥ 80 000/mm³) 12. Effective contraception 13. Written, dated and signed informed consent by the patient prior to any specific protocol procedure 14. Ability to comply with the protocol procedures 15. Patient affiliated to a social security system or beneficiary of the same
Exclusion criteria
1. Poorly differentiated tumours (NEC) 2. Mixed NeuroEndocrine Non NeuroEndocrine tumors (MiNEN) 3. Neoadjuvant treatment or treatment with chemotherapy regimen used for another malignancy 4. Pregnant women or breastfeeding women 5. ECOG performance status \> 1 6. Age \< 18 years 7. PanNET arising in a genetic syndrome with other NETs already diagnosed (NF1, VHL or MEN) 8. History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least five years 9. Severe renal insufficiency (measured GFR according to MDRD \< 30 ml/mn or nephrotic syndrome) or hepatic insufficiency (ALT / AST \> 2.5 x ULN or ALT/AST \> 5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin \> 2.5 x ULN) 10. Serum albumin \< 3.0 g/dL unless prothrombin time is within the normal range 11. Current treatment with another investigational drug 12. Unrecovered toxicity from surgery 13. Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the Investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study 14. Dihydropyrimidine dehydrogenase (DPD) deficiency or not done 15. Recent or concomitant treatment with brivudine 16. Hypersensitivity to Capecitabine or Temozolomide or to any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free survival (DFS) | time between randomization and the diagnosis of first recurrence or death, up to 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Specific survival | time from randomization to death due to disease progression, toxicity of the treatment or uncontrollable secretory syndrome, up to 5 years |
| Overall survival | time from randomization to death from any cause, up to 5 years |
| Toxicity assessment | at baseline, every month during the first year and then every year until the end of the study, up to 5 years |
| Time and pattern of recurrence | time from randomization to the detection of recurrence, up to 5 years |
| Quality of life assessment | evolution of the scores collected at baseline, every three months during one year, and then every year until the end of the study, up to 5 years |
Countries
France
Contacts
CONTACTEric BAUDIN, MD
CONTACTMatthieu FARON, MD
Outcome results
None listed