Personalized chemotherapy for advanced pancreatic cancer using gene signatures

Pilot Study of Personalized First-line Chemotherapy Choice for Patients With Advanced Pancreatic Adenocarcinoma Using Transcriptomic Signatures (PACsign)

This study is testing if using gene information from a liver biopsy can help doctors choose the best chemotherapy for people with advanced pancreatic cancer.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 85 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Institut Curie (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Clichy and 6 other locations)
• Trial ID: NCT05475366 on ClinicalTrials.gov

What this trial studies

This study aims to improve the effectiveness of first-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) by utilizing five transcriptomic signatures to predict sensitivity to specific chemotherapeutic agents. Patients will undergo a pre-therapeutic liver biopsy for RNA sequencing to determine the most suitable chemotherapy regimen, either FOLFIRINOX or Gem-nabP. The treatment decision will be based on the results of the transcriptomic analysis, allowing for a more personalized approach to therapy. Patients will be monitored for their response to treatment as part of the study.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed metastatic pancreatic ductal adenocarcinoma who have not received prior chemotherapy.

Not a fit: Patients with non-metastatic disease or those who have previously undergone chemotherapy are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly enhance the response rates to chemotherapy in patients with advanced pancreatic cancer.

How similar studies have performed: While personalized approaches to chemotherapy are being explored, this specific use of transcriptomic signatures for PDAC treatment is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
2. 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.
3. Histologically or cytologically proven Pancreatic Ductal Adenocarcinoma (PDAC).
4. Metastatic disease.
5. Measurable or evaluable lesions according to RECIST v1.1 criteria.
6. First-line therapy (previous neoadjuvant/adjuvant chemotherapy not allowed).
7. Age ≥ 18 years (no upper limit, patients ≥ 75 years old must have a G8 score ≥ 14).
8. 3\. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
9. Availability of tumor tissue sample from the primary pancreatic tumor or liver metastasis (chemo-naïve) before inclusion in step 1.
10. Adequate organ function, as defined by the following (blood test ≤ 7 days prior to inclusion):

    1. Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (≤ 5 ULN in case of liver metastases)
    2. Total serum bilirubin ≤ 1.5 ULN
    3. Serum albumin ≥ 28 g/L
    4. Hemoglobin ≥ 9.0 g/dl
    5. Absolute neutrophil count (ANC) ≥ 1,500/μL
    6. Platelets ≥ 100,000/μL
    7. Creatinine clearance ≥ 50 mL/min (MDRD).
11. No Dihydropyrimidine dehydrogenase (DPD) deficiency (normal uracil level).
12. Life expectancy ≥ 3 months.
13. a. Evidence of post-menopausal status b. (or) negative urinary or serum pregnancy test for female pre-menopausal patients.
14. Registration in a National Health Care System.

Exclusion Criteria:

1. Concurrent enrolment in another interventional clinical study.
2. Previous treatment with chemotherapy for pancreatic cancer.
3. Uncontrolled massive pleural effusion or massive ascites.
4. Known deficiency in UGT1A1 (homozygous UGT1A1\*28 allele).
5. 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).
6. 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.
7. 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).
8. 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.
9. Live vaccine administration within 30 days prior to the first dose of study treatment.
10. Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
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. 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.
13. Major surgical procedure (as defined by the Investigator) within 4 weeks prior to the first dose of trial treatment.
14. Pregnancy/lactation.
15. Person under legal protection or tutelage or guardianship.

Where this trial is running

Clichy and 6 other locations

• Hôpital Beaujon — Clichy, France (RECRUITING)
• Hôpital HENRI MONDOR — Créteil, France (RECRUITING)
• Hôpital Claude Hurriez — Lille, France (RECRUITING)
• Institut Paoli-Calmettes — Marseille, France (RECRUITING)
• CHU Robert Debré — Reims, France (RECRUITING)
• Institut Curie — Saint-Cloud, France (RECRUITING)
• Hôpital PAUL BROUSSE 12 Avenue Paul Vaillant Couturier — Villejuif, France (RECRUITING)

Study contacts

• Study coordinator: Cindy NEUZILLET, MD, PhD

Conditions: Carcinoma, Pancreatic Ductal, Prognosis, Transcriptomic signatures, Personalized first-line chemotherapy, Metastatic PDAC