Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, Resectable Pancreatic Adenocarcinoma
Conditions
Keywords
Neoadjuvant Therapy, Adjuvant Chemotherapy, Oxaliplatin, Irinotecan, Leucovorin, Fluorouracil, Pancreatic Neoplasms, Pancreatectomy
Brief summary
The PREOPANC-3 study is a randomized, multicenter, phase 3 trial. Patients with resectable pancreatic cancer will be randomly assigned (1:1) to 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (arm 1) or to upfront surgery followed by 12 cycles of adjuvant mFOLFIRINOX (arm 2). The primary objective of the trial is to determine whether perioperative mFOLFIRINOX improves overall survival compared with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer.
Interventions
DRUGLeucovorin Calcium
IV
DRUGFluorouracil
IV
DRUGIrinotecan Hydrochloride
IV
DRUGOxaliplatin
IV
PROCEDUREResection
Open or minimally-invasive pancreatectomy.
Sponsors
Erasmus Medical Center
Dutch Pancreatic Cancer Group
Dutch Cancer Society
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically (Bethesda 5 or 6) confirmed pancreatic ductal adenocarcinoma. * Resectable tumor according to Dutch Pancreatic Cancer Group criteria: no arterial contact and venous contact with the superior mesenteric vein or portal vein of 90 degrees or less * No evidence for metastatic disease * WHO performance status of 0 or 1 * Ability to undergo surgery and mFOLFIRINOX chemotherapy * Leucocytes (WBC) ≥ 3.0 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Hemoglobin ≥ 6.0 mmol/l * Renal function: eGFR ≥ 40 ml/min * Age ≥ 18 years * Written informed consent
Exclusion criteria
* Prior radiotherapy, chemotherapy, or surgery for pancreatic cancer. * Prior chemotherapy precluding mFOLFIRINOX. * Previous malignancy (excluding non-melanoma skin cancer, pancreatic neuroendocrine tumor (pNET) \<2cm, and gastrointestinal stromal tumor (GIST) \<2cm), unless no evidence of disease and diagnosed more than 3 years before diagnosis of pancreatic cancer, or with a life expectancy of more than 5 years from date of inclusion. * Pregnancy or lactation. * Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to 5 years after randomization. | The time between randomization and death from any cause. Patients alive at last follow-up are censored. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | Up to 5 years after randomization. | The time between randomization and locoregional progressive disease before or during treatment (resulting in irresectability), the occurrence of distant metastases, recurrent pancreatic cancer after surgery or death from any cause. Patients alive and free of these events at last follow-up are censored. |
| Distant metastases free survival | Up to 5 years after randomization. | The time between randomization and the occurrence of distant metastases or death from any cause. Patients alive and free of these events at last follow-up are censored. |
| Locoregional progression free survival | Up to 5 years after randomization. | The time between randomization and locoregional progression before or during treatment (resulting in irresectability), locoregional recurrence after resection or death from any cause. Patients alive and free of these events at last follow-up are censored. |
| Distant metastases free interval | Up to 5 years after randomization. | The time between randomization and the occurrence of distant metastases. Distant metastases are considered an event and patients are censored at death or last follow-up when without this event. |
| Locoregional progression free interval | Up to 5 years after randomization. | The time between randomization and locoregional progression before or during treatment (resulting in irresectability), or locoregional recurrence after resection. Locoregional progressive disease before or during treatment or locoregional recurrence after resection are considered an event and patients are censored at death or last follow-up when free of these events. |
| Chemotherapy start rate | 4 months | The percentage of patients who received at least one cycle of scheduled chemotherapy. |
| Number of chemotherapy cycles received. | 9 months | The number of mFOLFIRINOX cycles patients received. |
| Chemotherapy completion rate | 9 months | The percentage of patients who completed all cycles of scheduled chemotherapy. |
| Dose intensity | 9 months | The amount of drug delivered as a percentage of planned dose according to the protocol. |
| Staging laparoscopy rate | At the time of surgery. | The percentage of patients that actually underwent a staging laparoscopy, regardless whether a surgical exploration or resection was performed. |
| Laparoscopy yield | At the time of surgery. | The percentage of patients that underwent staging laparoscopy and were diagnosed with metastatic or unresectable disease during this procedure. |
| Surgical exploration rate | At the time of surgery. | The percentage of patients who underwent a surgical exploration (open or minimally-invasive), regardless whether a resection was performed. |
| Resection rate | At the time of surgery. | The percentage of patients that underwent a curative-intent resection. |
| Microscopically margin-negative (R0) resection rate | At the time of surgery. | The percentage of patients that underwent a microscopically margin-negative (R0) resection. The resection is considered R0 if there is no tumor within 1 mm of the margins. |
| Lymph node-negative (N0) resection rate | At the time of surgery. | The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen. |
| Pathologic response | At the time of surgery. | Tumor regression score in the surgical specimen |
| Adverse events as assessed by the CTCAE version 5.0 | Until 30 days after last chemotherapy. | Adverse events are assessed during neoadjuvant therapy and adjuvant therapy. |
| Postoperative complications | Up to 90 days after surgery. | According to the Clavien-Dindo classification and by the International Study Group of Pancreatic Surgery and International Study Group of Liver Surgery. |
| Serum CA 19-9 and CEA response | 9 months | The change in carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) after surgery and after 4, 8, and 12 cycles of mFOLFIRINOX compared to baseline. |
| Clinical response rate according to RECIST criteria version 1.1 | At the time of surgery. | Response comparing baseline and restaging after 4 and 8 cycles of mFOLFIRINOX |
| Patient reported cancer-specific health-related Quality of Life (HRQoL) as assessed using the EORTC QLQ-C30 | Up to 5 years after randomization. | At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year |
| Patient reported non-disease specific HRQoL as assessed using the EQ-5D-5L | Up to 5 years after randomization. | At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year |
| Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26 | Up to 5 years after randomization. | At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year |
| Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS) | Up to 5 years after randomization. | At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year |
| Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20 | Up to 5 years after randomization. | At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year |
| Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS) | Up to 5 years after randomization. | At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year |
| Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire | Up to 5 years after randomization. | At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year |
Countries
Netherlands, Sweden
Contacts
PRINCIPAL_INVESTIGATORBas Groot Koerkamp, MD, PhD
Erasmus MC University Medical Center
Outcome results
None listed