Personalized First-line Chemotherapy Choice in Advanced Pancreatic Adenocarcinoma Using Transcriptomic Signatures

NCT05475366 | Recruiting

• 1 other identifier: IC 2021-15
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 7

Brief Summary

The aim of this study is to assess the clinical value of 5 transcriptomic signatures prognostic of chemotherapeutic sensitivity to improve the Objective Response Rate (ORR) of first-line (L1). Chemotherapy regimen (FOLFIRINOX vs Gem-nabP) will be selected based on transcriptomic signatures applied to the pre-therapeutic liver biopsy of newly diagnosed PDAC patients.

Conditions

Carcinoma, Pancreatic Ductal; Prognosis

Keywords

Transcriptomic signatures; Personalized first-line chemotherapy; Metastatic PDAC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) at 4 months based on thorax-abdomen-pelvis (TAP) CT scan every 8 weeks according to RECIST v1.1.

  ORR, defined as the percentage of patients whose disease decreased by at least 30% (partial response - PR) and/or disappeared (complete response - CR) under treatment among patients who start treatment.

  4 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  18 months

• Overall Survival (OS)

  18 months

• Disease Control Rate (DCR)

  18 months

• Treatment-related severe (grade 3-5) toxicities

  18 months

• Feasibility of study procedure

  12 months

Study Arms (1)

Molecular screening for prediction of response

EXPERIMENTAL

L1 chemotherapy regimen (FOLFIRINOX vs Gemcitabine plus nab-paclitaxel (GemnabP)) will be selected based on transcriptomic signatures applied to the pre-therapeutic biopsy of newly diagnosed PDAC patients.

Other: Clinical value of 5 transcriptomic signatures to personalize the therapeutic decision for L1 in PDAC; Other: Biomarkers of tumor signatures (translational studies)

Interventions

Biomarkers of tumor signatures (translational studies) OTHER

Blood (serum and plasma) will be drawn at baseline, week 8, and tumor progression in order to look for surrogate biomarkers of tumor signatures in liquid biopsy

Molecular screening for prediction of response

Clinical value of 5 transcriptomic signatures to personalize the therapeutic decision for L1 in PDAC OTHER

Formalin-Fixed Paraffin-Embedded (FFPE) samples will be centralized in which nucleic acids extraction (DNA+RNA) and FFPE-compatible RNA-sequencing will be performed in real-time (≤28 days). RNAseq reads will be processed and all 5 transcriptomic signatures will be applied for prediction of response to 5FU, oxaliplatin, irinotecan, gemcitabine and taxane. In addition, biomarkers status will be obtained for all patients as part of good clinical practice.

Molecular screening for prediction of response

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Histologically or cytologically proven Pancreatic Ductal Adenocarcinoma (PDAC).
• Metastatic disease.
• Measurable or evaluable lesions according to RECIST v1.1 criteria.
• First-line therapy (previous neoadjuvant/adjuvant chemotherapy not allowed).
• Age ≥ 18 years (no upper limit, patients ≥ 75 years old must have a G8 score ≥ 14).
• \. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (≤ 5 ULN in case of liver metastases)
• Total serum bilirubin ≤ 1.5 ULN
• Serum albumin ≥ 28 g/L
• Hemoglobin ≥ 9.0 g/dl
• Absolute neutrophil count (ANC) ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Creatinine clearance ≥ 50 mL/min (MDRD).

You may not qualify if:

• Concurrent enrolment in another interventional clinical study.
• Previous treatment with chemotherapy for pancreatic cancer.
• Uncontrolled massive pleural effusion or massive ascites.
• Known deficiency in UGT1A1 (homozygous UGT1A1\*28 allele).
• Active bacterial, viral, or fungal infection requiring systemic therapy, including tuberculosis, hepatitis B (known positive Hepatitis B Virus surface antigen (HBsAg) result), hepatitis C (with positive RNA), Sars-Cov-2 or human immunodeficiency virus (positive HIV 1/2 antibodies).
• Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri.
• 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).
• Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure or coronary disease, peripheral artery disease, severe chronic obstructive pulmonary disease, decompensated cirrhosis, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• Live vaccine administration within 30 days prior to the first dose of study treatment.
• Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• 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.
• 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 4 weeks prior to the first dose of trial treatment.
• Pregnancy/lactation.
• Person under legal protection or tutelage or guardianship.

Sponsors & Collaborators

• Institut Curie: lead

Study Sites (7)

Hôpital Beaujon

Clichy, 92210, France

RECRUITING

Hôpital HENRI MONDOR

Créteil, 94010, France

RECRUITING

Hôpital Claude Hurriez

Lille, 59037, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13573, France

RECRUITING

CHU Robert Debré

Reims, 51092, France

RECRUITING

Institut Curie

Saint-Cloud, 92210, France

RECRUITING

Hôpital PAUL BROUSSE 12 Avenue Paul Vaillant Couturier

Villejuif, 94800, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Pancreatic Ductal; Anophthalmia with pulmonary hypoplasia

Interventions

Long Interspersed Nucleotide Elements

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Retroelements; Interspersed Repetitive Sequences; Repetitive Sequences, Nucleic Acid; Base Sequence; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genome Components; Genome

Study Officials

• Cindy NEUZILLET, MD, PhD

  Hôpital PAUL BROUSSE

  STUDY DIRECTOR

Central Study Contacts

Cindy NEUZILLET, MD, PhD

CONTACT

+33 (0) 6 82 55 04 92; cindy.neuzillet@aphp.fr

Marie-Emmanuelle Legrier

CONTACT

drci.promotion@curie.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: July 26, 2022
• Study Start: December 12, 2022
• Primary Completion (Estimated): December 11, 2028
• Study Completion (Estimated): December 11, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (7)