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

NCT05083247 | Recruiting Phase 2 DMC

• 1 other identifier: ERA 001
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 10

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.

Conditions

Pancreatic Neoplasm; Pancreatic Adenocarcinoma; Borderline Resectable Pancreatic Adenocarcinoma

Keywords

borderline resectable pancreatic cancer; neoadjuvant therapy; stereotactic body radiation therapy; chemotherapy

Outcome Measures

Primary Outcomes (2)

• Disease free survival

  Defined as time from randomisation to the first documentation of event where events considered are 1) disease progression, per RECIST, prior to surgery, 2) discovery of hepatic or peritoneal carcinomatosis during surgical exploration, 3) recurrent disease following R0-R1 surgery, or 4) death due to any cause.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks

• R0 Resection rate

  Defined as the proportion of eligible randomised patients in whom a R0 resection was achieved during surgery after neoadjuvant treatment with FOLFIRINOX +/- iHD-SBRT. R0 resection indicates a microscopically margin-negative resection (\>1 mm) from the inked margins (pancreatic transection, vascular and posterior circumferential resection margins).

  up to 12 months

Secondary Outcomes (12)

• Resection rate

  up to 12 months

• Pathologic complete/major response (pCR)

  up to 12 months

• Complete feasibility of the therapeutic sequence

  up to 12 months

• Overall survival (OS)

  Defined as the time interval between randomisation and death, assessed up to 60 months

• Locoregional failure free interval (LFFI)

  defined as the time interval between the randomisation and the 1st documented date of locoregional failure, assessed up to 60 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

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).

Drug: mFOLFIRINOX or Gemcitabine nab-paclitaxel; Procedure: Surgery

Arm B

EXPERIMENTAL

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)

Drug: mFOLFIRINOX or Gemcitabine nab-paclitaxel; Radiation: Isotoxic High-Dose (iHD)-SBRT; Procedure: Surgery

Interventions

mFOLFIRINOX or Gemcitabine nab-paclitaxel DRUG

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

Also known as: mFFX or Gem/Nab-p

Arm A; Arm B

Isotoxic High-Dose (iHD)-SBRT RADIATION

Radiation therapy

Arm B

Surgery PROCEDURE

Surgery

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Erasme University Hospital: lead
• Jules Bordet Institute: collaborator
• Belgian Group of Digestive Oncology: collaborator
• University Hospital St Luc, Brussels: collaborator

Study Sites (10)

Uza Antwerp

Antwerp, 2650, Belgium

RECRUITING

Hopital Erasme, HUB

Brussels, 1070, Belgium

RECRUITING

Jules Bordet Institute, HUB

Brussels, 1070, Belgium

RECRUITING

CHIREC

Brussels, 1160, Belgium

RECRUITING

Cliniques Universitaires St luc

Brussels, 1200, Belgium

RECRUITING

UZ Gent

Ghent, 9000, Belgium

NOT YET RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

Pôle Hospitalier Jolimont

La Louvière, 7100, Belgium

RECRUITING

Clinique Chc Montlégia

Liège, 4000, Belgium

RECRUITING

CHU Ambroise Paré

Mons, 7000, Belgium

RECRUITING

Related Publications (4)

• 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.

  PMID: 33553589 BACKGROUND

• 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.

  PMID: 34691244 BACKGROUND

• 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.

  PMID: 36497212 BACKGROUND

• 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.

  PMID: 37735634 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Jean-Luc Van Laethem, MD

  Erasme Hospital, ULB

  STUDY CHAIR

• Christelle Bouchart, MD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-Luc Van Laethem, MD PhD

CONTACT

003225553714; jl.vanlaethem@erasme.ulb.ac.be

Mia Persoons

CONTACT

003225553016; mia.persoons@erasme.ulb.ac.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: comparative randomised phase II

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 19, 2021
• Study Start: March 24, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 23, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (10)