Maintenance With OSE2101 Plus FOLFIRI, or FOLFIRI After FOLFIRINOX-based Induction Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (TEDOPAM)
- Conditions
- locally advanced or metastatic Pancreatic ductal adenocarcinoma
- Registration Number
- 2024-518139-12-00
- Lead Sponsor
- Association Gercor
- Brief Summary
To assess the overall survival (OS) of OSE2101 plus FOLFIRI or FOLFIRI alone as maintenance therapy in patients with locally advanced or metastatic PDAC, HLA-A2 positive, having experienced 4-month induction chemotherapy with FOLFIRINOX without disease progression
- Detailed Description
Current standard of care for patients with advanced pancreatic ductal adenocarcinoma (PDAC) is chemotherapy, preferential regimen being FOLFIRINOX (5FU, leucovorin, irinotecan, and oxaliplatin) in fit patients (PS 0-1, bilirubin \< 1.5 ULN). The question of how and when the FOLFIRINOX regimen and doses can be deescalated after a period of disease control (i.e. maintenance therapy) remains unanswered. In routine practice, oxaliplatin is usually stopped after 6-8 cycles due to limiting neuropathy, and the fluoropyrimidine is continued, either alone or, more frequently, in combination with irinotecan (FOLFIRI regimen), until disease progression.
Immune therapies have opened new opportunities in cancer therapy. However, results of immunotherapy in PDAC have been disappointing so far, with failure of checkpoint inhibitor monotherapies (anti-CTLA4 and anti-PD-L1 monoclonal antibodies \[mAb\]) in progressive advanced PDAC, while monovalent vaccines were demonstrated to be safe but with limited activity.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 106
Signed and dated informed consent document, willing and able to comply with protocol requirements
Recurrent or advanced disease not amenable to surgery with curative intent (previous resection of primary tumor allowed)
Measurable or evaluable (radiologically detectable disease which does not fulfill RECIST criteria for measurable disease) lesions according to RECIST v1.1 criteria (CT-scan < 4 weeks)
Stable disease or tumor response according to RECIST v1.1 after a 4-month (8 cycles, CT-scan at C8 ± 2 weeks) course of first-line FOLFIRINOX or modified FOLFIRINOX induction chemotherapy
Have archival tissue sample that has been identified and confirmed as available for study, or newly obtained core or excisional biopsy of a tumor lesion
Adequate organ function, as defined by the following: - Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) - Total serum bilirubin < 1.5 ULN - Prothrombin ratio > 70% - Serum albumin ≥ 2.8 g/dL - Hemoglobin ≥ 10,0 g/dl - White blood cell count (WBC) ≥ 3,000/μL - Absolute neutrophil count (ANC) ≥ 1,500/μL - Platelets ≥ 100,000/μL - Serum creatinine ≤ 1.5 ULN or creatinine clearance > 50 mL/min (MDRD)
Life expectancy ≥ 3 months
Women participants of childbearing potential must have a negative serum pregnancy test within the 3 days prior to the first treatment administration until 180 days after the last dose of FOLFIRI, and after the last dose of OSE2101 for women and 90 days after the last dose of OSE2101 for men. Both women participants of childbearing potential and men participants who are sexually active with women of childbearing potential must agree to use a reliable method of birth control (i.e. pregnancy rate < 1% per year);
Registration in a national health care system (PUMA included)
Histologically or cytologically proven PDAC
Age ≥ 18 years
ECOG Performance Status (PS) 0-1
HLA-A2 genotype
Obstructive jaundice (bilirubin > 1.5 ULN) without adequate biliary drainage
Evidence of interstitial lung disease, any active, non-infectious pneumonitis, or known active tuberculosis
Active uncontrolled infection, or current unstable or uncompensated respiratory or cardiac conditions, or bleeding
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
Live vaccine administration within 30 days prior to the first dose of study treatment
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator
Known or suspected drug hypersensitivity to OSE2101 vaccine
Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product
Treatment with any investigational medicinal product within 28 days prior to study entry
Prior intolerance/severe toxicity with 5FU or irinotecan (including DPD and UGT1A1 deficiency)
Any systemic steroid therapy (> 10 mg daily dose of prednisone or equivalent) for more than seven days one month before inclusion
Pregnancy/lactation
Tutelage or guardianship
Allograft recipient
Active HBV, HCV, or HIV infection
Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri
Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of neuropathy, alopecia, and the laboratory values defined in the inclusion criteria
Known active central nervous system metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids at a dose > 10 mg/day of prednisone or equivalent for at least 14 days prior to trial treatment
Uncontrolled massive pleural effusion or massive ascites
History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Evaluable patients for OS rate at 12 months will be patients alive at 12 months and patients dead within 12 months; patients lost to follow-up before 12 months without confirmation of death will be non-evaluable. The OS is defined according to the DATECAN consensus as the time from randomization to death for any reason. In the absence of confirmation of death, survival time will be censored at the date of the last clinical assessment. Evaluable patients for OS rate at 12 months will be patients alive at 12 months and patients dead within 12 months; patients lost to follow-up before 12 months without confirmation of death will be non-evaluable. The OS is defined according to the DATECAN consensus as the time from randomization to death for any reason. In the absence of confirmation of death, survival time will be censored at the date of the last clinical assessment.
- Secondary Outcome Measures
Name Time Method PFS by centralized review of CT-scan imaging. PFS by centralized review of CT-scan imaging.
All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Response according to RECIST v1.1 77 (centralized review of CT-scan imaging) Response according to RECIST v1.1 77 (centralized review of CT-scan imaging)
HRQoL assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire HRQoL assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire
Q-TWiST Q-TWiST
Potential predictive biomarkers (blood and tumor tissue) Potential predictive biomarkers (blood and tumor tissue)
Immune-related AEs (imAEs) according to sarcopenia Immune-related AEs (imAEs) according to sarcopenia
Trial Locations
- Locations (34)
Hopital Prive Jean Mermoz
🇫🇷Lyon, France
Centre De Recherche En Cancerologie De Lyon
🇫🇷Lyon, France
CHU Henri Mondor
🇫🇷creteil, France
Institut De Cancerologie De Lorraine
🇫🇷Vandouvre Les Nancy, France
CHU Amiens-Picardie - Site Sud
🇫🇷Salouel, France
Centre Hospitalier Regional Universitaire De Tours
🇫🇷Chambray Les Tours, France
Centre Hospitalier De Cholet
🇫🇷Cholet, France
Hôpital Franco-Britannique-Fondation Cognacq-Jay
🇫🇷Levallois-Perret, France
Centre Hospitalier Et Universitaire De Limoges
🇫🇷Limoges, France
Institut Paoli Calmettes
🇫🇷Marseille, France
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