Clinical trial NCT03806309: Maintenance With OSE2101 Plus FOLFIRI, or FOLFIRI After FOLFIRINOX-based Induction Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma
Official title: A Randomized Non-comparative Phase II Study of Maintenance Therapy With OSE2101 Plus FOLFIRI, or FOLFIRI After Induction Therapy With FOLFIRINOX in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (TEDOPaM-D17-01 PRODIGE 63 Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Pancreatic Ductal Adenocarcinoma
Locally Advanced Cancer
Metastatic Cancer
Keywords: Immunotherapy
Chemotherapy
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
Collaborators: name: OSE Immunotherapeutics
First posted: 2019-01-16
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: TEDOPAM is a randomized (1.1.1) non-comparative phase II study. This study will assess the efficacy and safety of OSE2101 alone or in combination with nivolumab followed by FOLFIRI reintroduction, versus FOLFIRI as maintenance therapy in patients with advanced PDAC after induction therapy with FOLFIRINOX.

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.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent document, willing and able to comply with protocol requirements,
2. Histologically or cytologically proven pancreatic ductal adenocarcinoma,
3. Age ≥ 18 years,
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1,
5. Human Leukocyte Antigen (HLA-A2) genotype,
6. Recurrent or advanced disease not amenable to surgery with curative intent (previous resection of primary tumor allowed),
7. 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),
8. Stable disease or tumor response according to RECIST v1.1 after a 4-month (8 cycles) course of first-line FOLFIRINOX or modified FOLFIRINOX induction chemotherapy,
9. 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,
10. 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 (Modification of diet in renal disease \[MDRD\]),
11. Life expectancy ≥ 3 months,
12. Women participants of childbearing potential must have a negative serum pregnancy test within the 3 days prior to the first treatment administration. 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) until 6 months after the last dose of FOLFIRI, and 90 days after the last dose of OSE2101,
13. Registration in a national health care system (PUMA included).

Exclusion Criteria:

1. Obstructive jaundice (bilirubin \> 1.5 ULN) without adequate biliary drainage,
2. Allograft recipient,
3. Active HBV (hepatitis B virus), HCV (hepatitis C virus ), or HIV infection, Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive HBc (hepatitis B core antigen) antibody test are eligible.

   Note: Patients positive for HCV antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA).
4. 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,
5. 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,
6. 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 neurological 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,
7. Uncontrolled massive pleural effusion or massive ascites,
8. Evidence of interstitial lung disease, any active, non-infectious pneumonitis, or known active tuberculosis,
9. Active uncontrolled infection, or current unstable or uncompensated respiratory or cardiac conditions, or bleeding,
10. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study,
11. 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,
12. Known or suspected drug hypersensitivity to OSE2101 vaccine,
13. 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,
14. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product, Note: Local surgery of isolated lesions for palliative intent is acceptable.
15. Treatment with any investigational medicinal product within 28 days prior to study entry,
16. Prior intolerance/severe toxicity with 5-fluorouracil (5-FU) or irinotecan (including dihydropyrimidinedehydrogenase \[DPD\] and UGT1A1 deficiency),
17. Pregnancy/lactation,
18. Tutelage or guardianship.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: At 12 months
Secondary outcomes:
measure: Progression free survival (PFS) by centralized review of CT-scan imaging.
timeFrame: assessed up to 60 months
measure: Rate of patients with success of the strategy (SSR)
timeFrame: At 6 months
measure: Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCICTCAE] v5.0
timeFrame: from signature of informed consent to 28 days after the last administration of the investigational product in Arm A and B and 100 days after the last administration of the investigational product in Arm C.
measure: Objective response rate (ORR)
timeFrame: assessed up to 60 months
measure: Health-related Quality of life (HRQoL) evaluation assessed by EORTC QLQ (quality of life questionnaire) -C30 questionnaire
timeFrame: Baseline, Month 2, Month 4, Month 6, Month 8, Month 10, Month 12, Month 14, Month 16, Month 18, Month 20, Month 22, Month 24 (until the date of first documented progression or date of death, assessed up 60 months)
measure: Estimate the Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment (Q-Twist) for each participant
timeFrame: assessed up to 60 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Clinique de l'Europe
city: Amiens
country: France
facility: Hôpital Sud CHU Amiens
city: Beauvais
country: France
facility: CH Beauvais
city: Besançon
country: France
facility: CHRU Jean Minjoz
city: Bordeaux
country: France
facility: Clinique Tivoli Ducos
city: Brest
country: France
facility: CHU Morvan
city: Creil
country: France
facility: GHPSO Site de Creil
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Dijon
country: France
facility: CHU Dijon
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: centre Léon Bérard
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Lyon
country: France
facility: Hôpital la Croix Rousse
city: Lyon
country: France
facility: Hôpital Lyon Sud Hospices Civils de Lyon
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Hôpital Européen
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Poitiers
country: France
facility: CHU Poitiers
city: Reims
country: France
facility: CHU Robert Debré
city: Saint-Cloud
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Clinique Pasteur
city: Tours
country: France
facility: Hôpital TROUSSEAU
city: Vandœuvre-lès-Nancy
country: France
facility: Insitut de Cancérologie de Lorraine
Study officials:
affiliation: Institut Curie site de Saint Cloud
name: Cindy NEUZILLET, MD
role: PRINCIPAL_INVESTIGATOR
References: