Neoadjuvant Plus Adjuvant or Only Adjuvant Nab- Paclitaxel Plus Gemcitabine for Resectable Pancreatic Cancer

• Status: Active, not recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

Summary

NEONAX is an interventional, prospective, randomized, controlled, open label, two sided survival phase II studies against a fixed survival probability, with an unconnected analysis of the results in both experimental arms.

Determining the impact of 2 cycles of Perioperative nab-paclitaxel/gemcitabine followed by surgery and 4 cycles of adjuvant nab-paclitaxel/gemcitabine or 6 cycles of adjuvant nab-paclitaxel/gemcitabine on the Disease free survival (DFS) rate at 18 months post randomization

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIO-Studien-gGmbH
• Collaborators: Celgene; ClinAssess GmbH
• Treatments: Albumin-Bound Paclitaxel; Gemcitabine; Paclitaxel

Criteria

Inclusion criteria:

• Histologically or cytological confirmed, clearly resectable ductal adenocarcinoma of the pancreas (PDAC) ≤ cT3 with no prior tumor specific treatment.

• No evidence of metastases to distant organs (e.g. liver, peritoneum, lung).

• Resectable tumor. Determination of resectability based on spiral CT scans with both oral and i.v. contrast enhancement or on MRI using a recent consensus definition (Resectability: Clear fat planes around the celiac artery, hepatic artery and superior mesenteric artery.)

• Measurable tumor according to RECIST 1.1

• ECOG performance status 0 or 1

• Creatinine clearance ≥ 30 ml/min

• Serum total bilirubin level ≤ 2.5 x ULN (not necessary for enrollment or randomization, but before start of neoadjuvant chemotherapy in arm A)

• ALT and AST ≤ 2.5 x ULN (not necessary for enrollment or randomization, but before start of neoadjuvant chemotherapy in arm A)

• In case of biliary obstruction, biliary decompression is required if the patient was randomized to receive neoadjuvant chemotherapy (arm A)

• White blood cell count ≥ 3.5 x 106/ml, neutrophil granulocytes count ≥ 1,5 x 106/ml, platelet count ≥ 100 x 106/ml

• Signed informed consent incl. participation in translational research

• Age ≥ 18 years

Exclusion criteria:

• Borderline resectable PDAC by radiologic criteria

• Papillary cancer

• Neuroendocrine Cancer

• Tumor specific pre-treatment

• Local recurrence

• Peritoneal or other distant metastases

• Radiographic evidence of severe portal hypertension/cavernous transformation

• Infiltration of extrapancreatic organs (except duodenum)

• Ascites

• Gastric outlet obstruction

• Global respiratory insufficiency requiring oxygen supplementation

• Chronic infectious diseases, immune deficiency syndromes

• Premalignant hematologic disorders, e.g. myelodysplastic syndrome

• Disability to understand and sign written informed consent document

• Past or current history of malignancies except for the indication under this study and curatively treated:

• Basal and squamous cell carcinoma of the skin

• In-situ carcinoma of the cervix

• Other malignant disease without recurrence after at least 2 years of follow-up

• Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment

• Clinically relevant or history of interstitial lung disease, e.g. non-infectious pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan or chest x-ray.

• History of or evidence upon physical examination of CNS disease unless adequately treated (e.g. primary brain tumor, seizure not controlled with standard medical therapy or history of stroke).

• Pre-existing neuropathy > grade 1 (NCI CTCAE)

• Allogeneic transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy

• Severe non-healing wounds, ulcers or bone fractions

• Evidence of bleeding diathesis or coagulopathy

• Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and PTT < 1.5 ULN within 28 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution)

• Major surgical procedures, except open biopsy, nor significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgical procedure during the course of the study except for surgery of pancreatic cancer with curative intent and central intravenous line placement for chemotherapy administration.

• Pregnancy or breastfeeding women.

• Subjects with known allergies to the study drugs or to any of its excipients.

• Current or recent (within the 28 days prior randomization) treatment with another investigational drug or participation in another investigational study.

• Any psychological, familial, sociological or geographical condition potentially compromising compliance with the study protocol and the follow-up schedule; those conditions should be discussed with the patient prior to registration in the trial