Pancreatic Locally Advanced Irresectable Cancer Ablation

Not Applicable

Interventions: Procedure: Radiofrequency ablation (RFA)
Drug: Nab-paclitaxel plus Gemcitabine
Drug: FOLFIRINOX
Drug: Gemcitabine

Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary: The aim of the PELICAN trial is to investigate the survival benefit of RFA plus standard palliative chemotherapy as compared to palliative chemotherapy alone in patients with LAPC after 2 months of induction chemotherapy.

Detailed Description: Pancreatic cancer is the fifth leading cause of cancer-related death in the Netherlands. Each year around 900 patients in the Netherlands are diagnosed with irresectable locally advanced pancreatic cancer (LAPC), which has a median survival of 7.9 months. Standard treatment is palliative chemotherapy, which offers only a very limited survival benefit. Radiofrequency ablation (RFA) is a new ablative technique for LAPC, which is feasible and safe and has been suggested to improve survival. A randomized controlled trial has not yet been performed.

The aim of the PELICAN trial is to investigate the survival benefit of RFA plus standard palliative chemotherapy as compared to palliative chemotherapy alone in patients with LAPC after 2 months of induction chemotherapy. In a randomized controlled parallel-group superiority multicenter phase III clinical trial.

The intervention will be RFA followed by chemotherapy (gemcitabine monotherapy, nab-paclitaxel plus gemcitabine or FOLFIRINOX). The comparison will be standard palliative treatment consisting of gemcitabine monotherapy, nab-gemcitabine plus gemcitabine or FOLFIRINOX Primary endpoint: Overall survival. Secondary endpoints: Progression free survival, complications, pain, radiological tumor response, CA-19.9 and CEA response, quality of life, immunomodulation and total direct and indirect costs.

Recruitment & Eligibility

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the pancreas
Locally irresectable tumor
Primary tumor
Stable disease or partial response after 2 months of induction chemotherapy (according to RECIST)
Fit for chemotherapy as assessed by the medical oncologist, plus:
- Absolute neutrophil count: 1.5 × 109/L
- Platelet count: 100 × 109/L
- Renal function: creatinine clearance> 50 ml/min
- Transaminases ≤ 3 x ULN
Fit for surgery assessed by the treating surgeon and anesthesiologist
RFA technical feasible
Written informed consent
Age ≥ 18 years
Expert panel approval for randomisation

Exclusion Criteria

WHO performance status ≥ 3
Distant metastases on abdominal or thoracic CT scan*
Previous surgical, local ablative or radiotherapy for pancreatic cancer or chemotherapy which is inconsistent with the prescribed induction schedule according to protocol**
Stenosis of > 50% of the hepatic artery AND stenosis of >50% of the portal vein/ superior mesenteric vein
Second primary malignancy, except adequately treated non-melanoma skin cancer, in situ carcinoma of the cervix uteri or other malignancies treated at least 5 years previously without signs of recurrence.
Pregnancy
- Positive regional lymph nodes metastases are not a reason for exclusion. Lymph nodes are considered as regional, according to the consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Suspicious lymph nodes only on radiologic basis are not considered as metastasis. Only when suspicion is high due to large infiltration, pathological examination by FNA can be considered.
  - Surgical exploration is not a contra-indication for inclusion

Arm && Interventions

Group	Intervention	Description
Chemotherapy	Nab-paclitaxel plus Gemcitabine	Patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel plus gemcitabine or gemcitabine monotherapy
RFA	Nab-paclitaxel plus Gemcitabine	RFA: laparotomy is performed followed by radiofrequency ablation of the tumor. After recovery of the RFA patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel + gemcitabine or gemcitabine monotherapy
RFA	Radiofrequency ablation (RFA)	RFA: laparotomy is performed followed by radiofrequency ablation of the tumor. After recovery of the RFA patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel + gemcitabine or gemcitabine monotherapy
RFA	FOLFIRINOX	RFA: laparotomy is performed followed by radiofrequency ablation of the tumor. After recovery of the RFA patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel + gemcitabine or gemcitabine monotherapy
Chemotherapy	FOLFIRINOX	Patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel plus gemcitabine or gemcitabine monotherapy
Chemotherapy	Gemcitabine	Patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel plus gemcitabine or gemcitabine monotherapy
RFA	Gemcitabine	RFA: laparotomy is performed followed by radiofrequency ablation of the tumor. After recovery of the RFA patients will continue chemotherapy: FOLFIRINOX or nab-paclitaxel + gemcitabine or gemcitabine monotherapy

Primary Outcome Measures

Name	Time	Method
Overall survival	1.5 years	The period of time between randomization and death from any cause

Secondary Outcome Measures

Name	Time	Method
Tumor marker response	1.5 years	The response of the tumor marker between start of study treatment till end of follow up (or death)
Quality of Life questionnaire	1.5 years	The quality of life measured between start study treatment till end of follow up (or death)
Progression free survival	1.5 years	The period of time between randomization and disease progression or death (by any cause)
Radiological tumor response	1.5 years	The radiologic tumor response between start of study treatment till end of follow up (or death)
Complications	1.5 years	The occurence of any post-operative complications

Locations (2): Regionaal Academisch Kankercentrum Utrecht
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Utrecht, Netherlands
Amsterdam UMC
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Amsterdam, Noord-Holland, Netherlands