A Phase II, Plateform Study, Open-label, Evaluating the Efficacy and Safety of Neoadjuvant Treatment in Patients With Surgically Resecable Pancreatic Adenocarcinoma.

A Phase II, Plateform Study, Open-label, Evaluating the Efficacy and Safety of Neoadjuvant Treatment in Patients With Surgically Resecable Pancreatic Adenocarcinoma

This is an open master platform trial, which includes multi neo-adjuvant treatment trials, multi-center, national. This platform trial evaluates the major pathological response rate (mPR) after surgery.

Intervention: The procedure consists of administering a neoadjuvant treatment and then performing pancreatic surgery. The POWER platform trial aims to study several neoadjuvant treatments prior to surgery. They will be described in each sub-study, in appendix. The surgery will be performed on one day and the end of the treatment is the safety visit post-surgery (90 days after surgery).

Inclusion Criteria:

• Adult, age ≥ 18 years old at the time of signing the informed consent form.

• Documented informed consent.

• Histologically or cytologically confirmed pancreatic adenocarcinoma.

• Tumor deemed resectable based on local assessment.

• No evidence of distant metastases on CT scan or PET scan, as well as liver MRI prior to registration.

• ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.

• Adequate hematologic and organ function, defined by the following laboratory results obtained within 7 days prior to initiation of study treatment:

  1. Neutrophils ≥ 1.5 × 10⁹/L (≥ 1500/µL) without granulocyte colony-stimulating factor support.
  2. Platelet count ≥ 100 × 10⁹/L (≥ 100,000/µL) without transfusion.
  3. Hemoglobin ≥ 90 g/L (≥ 9 g/dL). Patients may be transfused to meet this criterion.
  4. AST, ALT, and ALP ≤ 3 × upper limit of normal (ULN).
  5. Total bilirubin ≤ 1.5 × ULN.Creatinine clearance ≥ 50 mL/min (calculated using the MDRD formula).
  6. Albumin ≥ 30 g/L (≥ 2.5 g/dL).
  7. For patients not receiving anticoagulant therapy: INR and aPTT ≤ 1.5 × ULN.

• Women of childbearing potential (WOCBP) must have a negative urine or serum β-HCG pregnancy test within 7 days prior to the registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required at 72-24 hours before starting the neo-adjuvant treatment. Sexually active female patients must agree to use two methods of effective contraception (cf. paragraph 7.10, one of them being a barrier method, or to abstain from sexual activity during the clinical investigation and for at least 6 months after last dose neoadjuvant treatment.

• Sexually active males patients must agree to use condom during the clinical investigation and for at least 6 months after the neo-adjuvant treatment. Also, it is recommended the childbearing potential female partner uses a highly effective method of contraception for the same duration (see paragraph 6.12 " Pregnancy and contraception ").

• Patients shall be eligible to undergo neo adjuvant treatment, surgery and tumor biopsies.

• Patients must be affiliated to a social security system or beneficiary of the same.

• Additional specific sub-study inclusion criteria: Patient should also meet the potential specific eligibility criteria of the sub-study for which they are screened.

Exclusion Criteria:

• Ongoing participation in clinical sub-study involving the use of an investigational product prior to registration in the sub-study.
• During participation in this study, patients will not receive any other clinical investigational drugs or any other anti-tumor drugs as describes on sub-study.
• Previous neoadjuvant or induction treatment for pancreatic cancer, including cytotoxic chemotherapy, immunotherapy, experimental therapy, or radiotherapy.
• Uncontrolled tumor-related pain.
• Pregnancy or breastfeeding Pregnant or breastfeeding women or intending to become pregnant during the study.
• Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
• No prior treatment including surgery, radiation therapy or systemic therapy for pancreatic adenocarcinoma.
• Patients with a history of another primary malignancy diagnosed or requiring treatment within the 2 years prior to the first administration of the study drug. The following prior malignancies are not considered exclusion criteria, provided they have been treated with curative intent: completely resected basal cell carcinoma or squamous cell carcinoma of the skin; localized prostate cancer; superficial or non-invasive bladder cancer; or carcinoma in situ of any site.

This should be discussed with the oncologist if necessary.

• Additional specific sub-study exclusion criteria: Patient should also meet the specific eligibility criteria of the sub-study for which they are screened.