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Trial record 4 of 11 for:    van laethem

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

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ClinicalTrials.gov Identifier: NCT05083247
Recruitment Status : Not yet recruiting
First Posted : October 19, 2021
Last Update Posted : October 19, 2021
Sponsor:
Collaborators:
Belgian Group of Digestive Oncology
University Hospital St Luc, Brussels
Universitair Ziekenhuis Brussel
University Hospital, Ghent
Pôle Hospitalier Jolimont
Academisch Ziekenhuis Groningen
Chirec
Information provided by (Responsible Party):
Erasme University Hospital

Brief Summary:

Background: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 both resectable and borderline resectable pancreatic tumors. In this setting, preoperative FFX seems to be feasible and can be prolonged by radiation therapy (chemoRT or SBRT) with promising benefits for patients in terms of R0 resection, local control and prolonged survival. However, the exact and best therapeutic sequence is not yet known and the additional role of adding radiation therapy to chemotherapy requires validation in randomised trials. We recently reported the feasibility and preliminary efficacy data of the whole therapeutic sequence combining preoperative FFX x 8 cycles (G-Nab-P in case of intolerance or no response ) prolonged by 5 days SBRT (35 Gy + SIB up to 50Gy at the tumour-vessel interfaces )[1, manuscript submitted]. We propose now to evaluate the impact and efficacy of adding isotoxic high-dose SBRT to preoperative neoadjuvant mFFX or Gem-NabP in patients with borderline or high-risk resectable pancreatic adenocarcinoma. We hypothesize that this full sequence strategy of pre-operative treatment is safe and feasible and will improve both the R0 resection rate and prognosis (DFS as primary end point) of pancreatic adenocarcinoma, especially by targeting the tumoural vascular encasement.

Objectives/endpoints: Evaluation of the safety and efficacy of pre-operative 8 cycles of modified FOLFIRINOX (or Gem-Nab-P) followed or not by SBRT in patients with borderline or at risk resectable pancreatic adenocarcinoma.

Primary objective:

• To compare DFS between arms

Secondary objectives:

To compare between the study arms:

  • Resection rate
  • R0 resection rate (> 1 mm)
  • Overall survival (OS)
  • Locoregional failure free interval (LFFI)
  • Distant metastases free interval (DMFI)
  • Complete feasibility of the therapeutic sequence
  • Pathologic complete response rate (pCR)
  • Toxicity (early and late)
  • Postoperative complications rate
  • Quality of life (QoL) assessment

Condition or disease Intervention/treatment Phase
Pancreatic Neoplasm Drug: mFOLFIRINOX or gemcitabine-nabpaclitaxel Phase 2

Detailed Description:

STUDY DESIGN Academic, prospective, randomised comparative, interventional study

Arm A: mFOLFIRINOX* x 8 cycles followed by surgery (+3-4w) Arm B: mFOLFIRINOX* x 6 cycles followed by iHD-SBRT then mFFX x2 followed by surgery (+3-4w)

Patients receive 8 cycles of modified FOLFIRINOX (consists of oxaliplatin, irinotecan, leucovorin and 5-FU). A full restaging (clinical, morphologic imaging, vascular involvement, biologics, CA 19.9) is performed. Non-progressive patients will be randomised after full restaging for receiving 5th and 6th cycles of chemo +/- stereotactic radiation. Adjuvant chemotherapy administration is indicated unless the patient's condition precludes it.

  • *: in case of CI or intolerance to FFX , gemcitabine-nab-paclitaxel regimen can be chosen or shifted to for 12 doses (6 then restaging then 3 to 6 followed by SBRT or immediate surgery)
  • In case of early intolerance or progression, chemotherapy shift is authorised

Treatment agents:

  1. 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 6-8 cycles every 2 weeks; *Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 for 3-4 cycles if unfit for mFFX).
  2. 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) after placement of EUS guided fiducials (Cook ECHO-TIP F 22G™ or polymarks™ charged 19G needle).
  3. Surgery: intra-abdominal exploration with or without pancreatectomy (with minimum multiple biopsies if complete surgery not feasible) performed 6 to 8 weeks after SBRT completion. The final decision to perform a pancreatectomy or not is left to the final judgment of the specialist surgeon at the time of surgery. Surgery will be performed in expert centers as defined by the INAMI-RIZIV convention.
  4. Adjuvant chemotherapy is indicated for at least 4 months unless the patient's condition precludes it (regimen left to investigator's choice) and should be started within 3 months after surgery.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: comparative randomised phase II
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose Stereotactic Body Radiation Therapy (iHD-SBRT) for Borderline (or at Risk) Resectable Pancreatic Adenocarcinoma: a Randomised Comparative Multicentre Phase II Study (STEREOPAC)
Estimated Study Start Date : November 1, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: preoperative chemotherapy
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-nabpaclitaxel
mFOLFIRINOX or gemcitabine-nabpaclitaxel +isotoxic high-dose SBRT: 5 x 7Gy with Simultaneous Integrated Boost (SIB) up to maximum 55Gy
Other Name: Radiation therapy iso toxic high dose SBRT

Experimental: preoperative chemotherapy + iso-toxic high dose stereotaxic body radiation therapy
mFOLFIRINOX for 6 cycles or gem-nabpaclitaxel for 3 cycles +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) after placement of EUS guided fiducials
Drug: mFOLFIRINOX or gemcitabine-nabpaclitaxel
mFOLFIRINOX or gemcitabine-nabpaclitaxel +isotoxic high-dose SBRT: 5 x 7Gy with Simultaneous Integrated Boost (SIB) up to maximum 55Gy
Other Name: Radiation therapy iso toxic high dose SBRT




Primary Outcome Measures :
  1. Disease free survival [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. R0 Resection rate [ Time Frame: Time point: up to 12 months ]
    Defined as the proportion of eligible randomised patients in whom an achieved R0 resection was achieved during surgery after neoadjuvant treatment with FOLFIRINOX +/- SBRT. R0 resection indicates a microscopically margin-negative resection (>1 mm) from the inked margins (pancreatic transection, vascular and posterior circumferential resection margins).

  2. Resection rate [ Time Frame: Time point: up to 12 months ]
    defined as the percentage of eligible randomised patients that underwent a curative-intent resection

  3. overall survival [ Time Frame: Defined as the time interval between randomisation and death;median ]
    Defined as the time interval between randomisation and death. 95% confidence interval will be estimated based on standard method.

  4. pathological response rate pCR [ Time Frame: Time point: up to 12 months ]
    Defined as the proportion of patients in whom a pCR or a major (<10% of residual tumour cells) was confirmed by histopathologic review of the surgical specimen.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinated process or body. Diagnosis should be verified by local pathologist
  • cTNM stage: T1-4N0-2M0
  • Confirmation of clinical and radiographic stage as borderline or at risk resectable* determined centrally by review of a diagnostic multisliced triphasic CT scan and/or MRI scan with contrast 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 unless the neoadjuvant regimen as described
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • No grade ≥ 2 neuropathy
  • Laboratory parameters as follows:
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • 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 and absence of cholestasis)

    • High-risk features for resectable disease as defined by NCCN (version 2.2021) and ASCO criteria, including: any vascular encasement, elevated CA 19.9, poor (nutritional) condition, large tumor (> 4cm) and/or involved loco-regional LN at CT, MRI or PET.

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

Additional exclusion criteria before randomisation:

  • 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.
  • 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 > 6.0 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 SBRT)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05083247


Contacts
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Contact: Jean-Luc Van Laethem, MD PhD 003225553714 jl.vanlaethem@erasme.ulb.ac.be
Contact: Mia Persoons 003225553016 mia.persoons@erasme.ulb.ac.be

Locations
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Belgium
Hopital Erasme
Brussels, Belgium, 1070
Contact: Jean-Luc Van Laethem, MD PhD    003225553714    jl.vanlaethem@erasme.ulb.ac.be   
Contact: Mia Persoons    003225553016    mia.persoons@erasme.ulb.ac.be   
Sponsors and Collaborators
Erasme University Hospital
Belgian Group of Digestive Oncology
University Hospital St Luc, Brussels
Universitair Ziekenhuis Brussel
University Hospital, Ghent
Pôle Hospitalier Jolimont
Academisch Ziekenhuis Groningen
Chirec
Investigators
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Principal Investigator: Jean-Luc Van Laethem, MD PhD Erasme Hospital, ULB
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Responsible Party: Erasme University Hospital
ClinicalTrials.gov Identifier: NCT05083247    
Other Study ID Numbers: ERA 001
First Posted: October 19, 2021    Key Record Dates
Last Update Posted: October 19, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Erasme University Hospital:
resectable borderline resectable pancreatic cancer
neoadjuvant therapy
stereotaxic body radiation therapy
chemotherapy
Additional relevant MeSH terms:
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Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Albumin-Bound Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs