Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma

NCT ID: NCT05083247

Last Updated: 2023-05-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 256 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-24
• Study Completion Date: 2030-12-31

Brief Summary

Surgical resection is the only potentially curative treatment for patients with pancreatic cancer with the aim of curative R0 resection and related improvement of survival. As a standard, surgery is usually followed by adjuvant therapy that improves survival but neoadjuvant therapy (NAT) is a rapidly emerging concept that needs to be explored and validated in terms of therapeutic options in borderline resectable pancreatic tumors. In this setting, preoperative FFX seems to be feasible and can be prolonged by radiation therapy. However, the exact and best therapeutic sequence is not yet known and the additional role of adding isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) to chemotherapy requires validation in randomised trials. We propose to evaluate the impact and efficacy of adding iHD-SBRT to preoperative neoadjuvant mFFX or Gem-NabP in patients with borderline resectable pancreatic adenocarcinoma.

Detailed Description

STEREOPAC is an multicenter, academic, prospective, randomised comparative, interventional study.

Patients receive 4 cycles of mFOLFIRINOX (or Gem-Nab-P)*. A full restaging (clinical, morphologic imaging, vascular involvement, biologics, CA 19.9) is performed. Non-progressive patients will be randomised (1:1) to

ARM A for receiving 4 additional cycles of chemo followed by surgery.

or to

ARM B for receiving 5th and 6th cycles of chemo then iHD-SBRT followed by a 7th (and optional 8th cycle) followed by surgery.

*: in case of CI or intolerance to mFFX, Gem-Nab-P regimen can be chosen or shifted to for 6 doses, then restaging, and then 3 doses followed by SBRT or 6 doses and immediate surgery)

Adjuvant chemotherapy administration is indicated unless the patient's condition precludes it.

Conditions

Pancreatic Neoplasm; Pancreatic Adenocarcinoma; Borderline Resectable Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

mFOLFIRINOX (oxaliplatin: 85 mg/m2, CPT-11: 165-180 mg/m2, folinic acid: 400mg/m2 and 5FU 2000-2400 mg/m2/46 h) regimen for 8 cycles every 2 weeks; or\*Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 for 4 cycles in case of unfit for mFFX).

Group Type: ACTIVE_COMPARATOR

mFOLFIRINOX or Gemcitabine nab-paclitaxel

Intervention Type: DRUG

oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV OR Gemcitabine IV Nab paclitaxel

Surgery

Intervention Type: PROCEDURE

Surgery

Arm B

mFOLFIRINOX for 6 cycles (or for 3 cycles Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 in case of unfit for mFFX) +Isotoxic high-dose SBRT: 5 x 7Gy with Simultaneous Integrated Boost (SIB) up to maximum 55Gy (= 1 week; starting ideally 2 weeks and maximum within 4 weeks after the end of chemotherapy)

Group Type: EXPERIMENTAL

mFOLFIRINOX or Gemcitabine nab-paclitaxel

Intervention Type: DRUG

oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV OR Gemcitabine IV Nab paclitaxel

Isotoxic High-Dose (iHD)-SBRT

Intervention Type: RADIATION

Radiation therapy

Surgery

Intervention Type: PROCEDURE

Surgery

Interventions

mFOLFIRINOX or Gemcitabine nab-paclitaxel

oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV OR Gemcitabine IV Nab paclitaxel

Intervention Type: DRUG

Isotoxic High-Dose (iHD)-SBRT

Radiation therapy

Intervention Type: RADIATION

Surgery

Surgery

Intervention Type: PROCEDURE

Other Intervention Names

mFFX or Gem/Nab-p

Eligibility Criteria

Inclusion Criteria

• Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinated process or body or tail. Diagnosis should be verified by local pathologist
• cTNM stage: T1-4N0-2M0
• Confirmation of clinical and radiographic stage as borderline resectable (CT scan and/or MRI scan with contrast according to the NCCN criteria) by a multidisciplinary board, composed by a dedicated oncological surgeon, radiologist and GI oncologist)
• Age > 18 years old
• No prior chemotherapy or radiation for pancreatic cancer
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• No grade ≥ 2 neuropathy
• Laboratory parameters as follows:
• Absolute neutrophil count (ANC) ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated GFR >45 mL/min
• Bilirubin ≤ 1.5 x ULN, including after adequate biliary stenting with metal stent (ideally 4 cm length)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5x ULN
• CA 19.9 < 2500 kU/l (baseline, prior to any therapy and absence of cholestasis)

Exclusion Criteria

• Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI or PET scan), histologically proven or at laparoscopy, including distal nodal involvement beyond the peripancreatic tissues (including non-regional lymph node involvement, ie: proven involvement of precaval lumbar lymphadenopathy(ies) and/or distant metastases
• Locally advanced disease as defined by the NCCN criteria (version 2.2021) ie > 180° arterial encasement (SMA and CA) unreconstructible venous encasement (SMV/PV) due to tumor involvement or occlusion of a long segment.
• CA 19.9 > 2500 kU/l (baseline and absence of cholestasis)
• Contraindication of surgery (general)
• Contraindications to receive FFX or gemcitabine-nab-Paclitaxel
• History of radiotherapy of the upper abdomen
• Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabin
• Patient < 18 years old
• Major surgery within 4 weeks of study entry
• Uncontrolled pre-existing disease including, but not limited to: active infection, symptomatic congestive heart failure, unstable angina, social / psychiatric disorder that would limit compliance to treatment and good understanding of the informed consent form
• Other concurrent anticancer therapies
• Existence of another active neoplasia other than basal cell carcinoma of the skin, cervical carcinoma in situ or non-metastatic prostate cancer. Patients who have a history of neoplasia must have been in remission for more than 5 years to be included in the protocol
• Pregnant or breastfeeding women; for women of childbearing potential only, a negative pregnancy test done < 7 days prior to registration is required. Using of reliable contraception for at least 1 month before treatment is mandatory
• Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study

• Progressive disease (RECIST or PETCT, including non locoregional nodal involvement and increase of CA 19.9 by 20%) after receiving 4 cycles of FFX (or G/NP), including shift chemotherapy in case of early progression.
• CA 19.9 > 1000 kU/l after neoadjuvant therapy.
• Presence of unmanageable toxicity during the first part of neoadjuvant chemotherapy (first 4 cycles or 6 doses of FFX or G/NP, respectively.
• Pancreatic tumour > 7.0 cm in greatest axial dimension at the time of randomization
• Massive invasion of the stomach or intestines and/or direct intestinal invasion of the mucosae visible at ultrasoundendoscopy
• Active gastric or duodenal ulcer disease at the time of randomization. Tolerated in case of antecedent without active ulcer (confirmation by endoscopy before iHD-SBRT)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jules Bordet Institute

OTHER

Sponsor Role: collaborator

Belgian Group of Digestive Oncology

OTHER

Sponsor Role: collaborator

University Hospital St Luc, Brussels

OTHER

Sponsor Role: collaborator

Erasme University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Luc Van Laethem, MD

Role: STUDY_CHAIR

Erasme Hospital, ULB

Christelle Bouchart, MD

Role: PRINCIPAL_INVESTIGATOR

Jules Bordet Institute

Locations

Uza Antwerp

Antwerp, , Belgium

Site Status: RECRUITING

Hopital Erasme, HUB

Brussels, , Belgium

Site Status: RECRUITING

Jules Bordet Institute, HUB

Brussels, , Belgium

Site Status: RECRUITING

CHIREC

Brussels, , Belgium

Site Status: RECRUITING

Cliniques Universitaires St luc

Brussels, , Belgium

Site Status: RECRUITING

UZ Gent

Ghent, , Belgium

Site Status: NOT_YET_RECRUITING

AZ Groeninge

Kortrijk, , Belgium

Site Status: RECRUITING

Pôle Hospitalier Jolimont

La Louvière, , Belgium

Site Status: RECRUITING

Clinique Chc Montlégia

Liège, , Belgium

Site Status: RECRUITING

CHU Ambroise Paré

Mons, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Jean-Luc Van Laethem, MD PhD

Role: CONTACT

jl.vanlaethem@erasme.ulb.ac.be

003225553714

Mia Persoons

Role: CONTACT

mia.persoons@erasme.ulb.ac.be

003225553016

Facility Contacts

Timon Vandamme, MD

Role: primary

Timon.vandamme@uza.be

Jean-Luc Van Laethem, MD

Role: primary

jl.vanlaethem@erasme.ulb.ac.be

003225553714

Mia Persoons

Role: backup

mia.persoons@erasme.ulb.ac.be

003225553016

Christelle Bouchart, MD

Role: primary

christelle.bouchart@bordet.be

+32 2 541 38 00

Francesco Puleo, MD

Role: primary

francesco_puleo@hotmail.com

Ivan Borbath, MD

Role: primary

ivan.borbath@uclouvain.be

Karen Geboes, MD

Role: primary

karen.Geboes@uzgent.be

Philippe Vergauwe, MD

Role: primary

philippe.vergauwe@azgroeninge.be

Alexandre Dermine, MD

Role: primary

alexandre.dermine@jolimont.be

Ghislain Houbiers, MD

Role: primary

ghislain.houbiers@chc.be

Marie Diaz, MD

Role: primary

marie.diaz@hap.be

References

Figueiredo M, Bouchart C, Moretti L, Mans L, Engelholm JL, Bali MA, Van Laethem JL, Eisendrath P. EUS-guided placement of fiducial markers for stereotactic body radiation therapy in pancreatic cancer: feasibility, security and a new quality score. Endosc Int Open. 2021 Feb;9(2):E253-E257. doi: 10.1055/a-1324-2892. Epub 2021 Feb 3.

Reference Type: BACKGROUND

PMID: 33553589 (View on PubMed)

Bouchart C, Engelholm JL, Closset J, Navez J, Loi P, Gokburun Y, De Grez T, Mans L, Hendlisz A, Bali MA, Eisendrath P, Van Gestel D, Hein M, Moretti L, Van Laethem JL. Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma. Ther Adv Med Oncol. 2021 Oct 19;13:17588359211045860. doi: 10.1177/17588359211045860. eCollection 2021.

Reference Type: BACKGROUND

PMID: 34691244 (View on PubMed)

Manderlier M, Navez J, Hein M, Engelholm JL, Closset J, Bali MA, Van Gestel D, Moretti L, Van Laethem JL, Bouchart C. Isotoxic High-Dose Stereotactic Body Radiotherapy (iHD-SBRT) Versus Conventional Chemoradiotherapy for Localized Pancreatic Cancer: A Single Cancer Center Evaluation. Cancers (Basel). 2022 Nov 22;14(23):5730. doi: 10.3390/cancers14235730.

Reference Type: BACKGROUND

PMID: 36497212 (View on PubMed)

Bouchart C, Navez J, Borbath I, Geboes K, Vandamme T, Closset J, Moretti L, Demetter P, Paesmans M, Van Laethem JL. Preoperative treatment with mFOLFIRINOX or Gemcitabine/Nab-paclitaxel +/- isotoxic high-dose stereotactic body Radiation Therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): study protocol for a randomised comparative multicenter phase II trial. BMC Cancer. 2023 Sep 21;23(1):891. doi: 10.1186/s12885-023-11327-x.

Reference Type: DERIVED

PMID: 37735634 (View on PubMed)

Other Identifiers

ERA 001

Identifier Type: -

Identifier Source: org_study_id