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

Launched by INSTITUT CURIE · Jul 25, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating how to choose the best first-line chemotherapy treatment for patients with advanced pancreatic cancer. The researchers want to see if they can improve treatment success by using specific genetic information from liver biopsies taken from patients before starting therapy. Participants will be assigned to receive one of two chemotherapy regimens, either FOLFIRINOX or Gem-nabP, based on this genetic testing.

To be eligible for the trial, participants must be at least 18 years old and have a confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma (PDAC). They should not have received any previous chemotherapy for this cancer. Participants will need to provide consent and be willing to follow the study plan, which includes treatment and follow-up visits. The trial is currently recruiting patients, and those who qualify can expect close monitoring during their treatment to assess how well the therapy is working. It's important to note that certain health conditions or treatments may exclude individuals from participating, so a thorough screening will take place.

Gender

ALL

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.