Molecularly Tailored Therapy in Advanced Pancreatic Cancer

Summary

Pancreatic cancer that has spread or cannot be removed by surgery is difficult to treat. Standard chemotherapy can slow the disease, but the cancer often starts growing again. Some pancreatic cancers have specific genetic changes that may be targeted by medicines already available in Denmark. It is not yet known whether selecting treatment based on these genetic changes is more effective than standard treatment. TAILOR-PANC is a randomized phase 2 study evaluating treatment guided by the molecular characteristics of the cancer. Adults with advanced pancreatic cancer whose disease has progressed during or after first-line chemotherapy may participate if molecular testing results are available. A national molecular tumor board will review these results and determine whether the cancer has a genetic change that can be matched to an available targeted treatment. Participants with a suitable genetic change will be randomly assigned in a 1:1 ratio to receive either the matched treatment recommended by the molecular tumor board or standard second-line treatment according to Danish guidelines. Participants without a suitable genetic change will receive standard treatment and will be followed in a separate observational group. Treatment will continue until the cancer progresses, unacceptable side effects occur, the participant withdraws consent, or the treating physician decides that treatment should stop. The main purpose of the study is to determine whether molecularly matched treatment delays cancer progression compared with standard treatment. The study will also evaluate overall survival, tumor response, side effects, and quality of life. Participants in the randomized groups will undergo scans, blood tests, and quality-of-life assessments at baseline and approximately every 8 weeks. Optional blood and tumor samples may also be collected through the BIOPAC project to explore biomarkers that could help predict treatment response or side effects.

Interventions

• Arm 1: Molecularly Tailored Therapy · DRUG

  Axitinib Crizotinib Dabrafenib Trametinib Erlotinib Larotrectinib Olaparib Pembrolizumab Pemigatinib Pertuzumab and trastuzumab (Phesgo9 Selpercatinib Vismodegib

• Arms 2: Standard-of-Care Therapy · DRUG

  Gemcitabine Nab-paclitaxel 5-Fluorouracil; 5-FU Calcium folinate Oxaliplatin Irinotecan Capecitabine

• Arm 3: Standard-of-Care Observational Cohort · DRUG

  Gemcitabine Nab-paclitaxel 5-Fluorouracil; 5-FU Calcium folinate Oxaliplatin Irinotecan Capecitabine

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

* Adult patients (aged 18 and over)
* PC confirmed by cytology or histology
* Written informed consent before any specific study procedures
* Available personalized report communicating the molecular testing results and detailed treatment options
* Participants must have received and progressed during or after 1 line of systemic chemotherapy in the advanced setting (gemcitabine or 5-FU based regimens) or within one year of the adjuvant/neoadjuvant treatment

Notes:

* In general, discontinuation of 1 drug in a multi-drug regimen and continuation of other drug(s), is considered part of the same line of treatment. Restarting the same regimen after a drug holiday or maintenance chemotherapy can also be considered part of the same line of treatment
* Switching from IV (5-FU) to an oral formulation (capecitabine) of the same drug is also considered part of the same line of treatment
* Minimum time from first systemic therapy for advanced PC to progression should be at least 2 months

  * ECOG Performance Status (PS) 0-2
  * Participants must have normal organ and marrow function as defined below:
* Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
* Platelet count ≥ 75 x 10⁹/L
* Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
* AST/ALT ≤ 5 x ULN
* Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 50 mL/min (using the Cockcroft-Gault formula)

  * Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated in the protocol
  * Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year

Exclusion Criteria:

* Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
* Allergies and Adverse Drug Reaction

  * History of allergy to study drug components
  * History of severe hypersensitivity reaction to any monoclonal antibody (applicable for participants to receive a monoclonal antibody in the trial)
* WOCBP who are pregnant or breastfeeding

Sites (4)

• Department of Oncology, Aalborg, Denmark
• Department of Oncology, Aarhus, Denmark
• Department of Oncology, Herlev, Denmark
• Department of Oncology, Vejle, Denmark