FOLFIRINOX Versus OncoSil™ in Addition to FOLFIRINOX in Patients With Locally Advanced Pancreatic Adenocarcinoma (TRIPP-FFX)

• ClinicalTrials.gov Identifier: NCT05466799
• Recruitment Status: Recruiting
• First Posted: July 20, 2022
• Last Update Posted: October 23, 2023
• Sponsor: OncoSil Medical Limited
• Information provided by (Responsible Party): OncoSil Medical Limited

Study Description

Brief Summary:

The purpose of the study is to assess the safety and efficacy of OncoSil™ when given in addition to standard FOLFIRINOX chemotherapy for treatment of Locally Advanced Pancreatic Cancer

Condition or disease	Intervention/treatment	Phase
Locally Advanced Pancreatic Cancer	Drug: FOLFIRINOX chemotherapy; Device: OncoSil™	Phase 2

Detailed Description:

Patients with Locally Advanced Pancreatic Cancer who have not received prior treatment to their pancreatic cancer will be informed about the study and the potential risks and benefits. After providing informed consent patients will undergo a 3 week screening period to confirm eligibility for the study. Patients who meet all eligibility criteria will be randomised 1:1 to either the control arm of up to 12 cycles of standard of care FOLFIRINOX chemotherapy or implantation of OncoSil™ in addition to the same FOLFIRINOX chemotherapy regimen. Patients will be followed for side side effects and palliative benefits during 4-8 weekly study visits and the objective efficacy of the treatment will be assessed by CT scans every 8 weeks. Quality of Life will be measured on various time-points using questionnaires.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-centre, Randomized Study of TaRgeted Intratumoural Placement of P-32 (OncoSil™) in Addition to FOLFIRINOX Chemotherapy vs FOLFIRINOX Alone in Patients With Unresectable Locally Advanced Pancreatic Adenocarcinoma.
• Actual Study Start Date: April 26, 2023
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: September 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: FOLFIRINOX Chemotherapy; Subjects in Arm A will receive up to 12 cycles of Standard Of Care FOLFIRINOX chemotherapy	Drug: FOLFIRINOX chemotherapy; Standard Of Care Chemotherapy regimen for treatment of Locally Advanced Pancreatic cancer; Other Name: Folinic Acid, 5-FU, Oxaliplatin, Irinotecan
Experimental: OncoSil™ in addition to FOLFIRINOX Chemotherapy; Subjects in Arm B will be implanted with the OncoSil™ device in addition to up to 12 cycles of Standard Of Care FOLFIRINOX chemotherapy	Drug: FOLFIRINOX chemotherapy; Standard Of Care Chemotherapy regimen for treatment of Locally Advanced Pancreatic cancer; Other Name: Folinic Acid, 5-FU, Oxaliplatin, Irinotecan; Device: OncoSil™; Implantation of OncoSil 32P microparticles into the Pancreatic Tumour under EUS guidance; Other Name: Phosphorous-32 microparticles

Outcome Measures

Primary Outcome Measures :

1. Safety and Tolerability [ Time Frame: Through study completion, an average of 18 months ]
   The primary analysis for safety of OncoSil™ is defined by the Adverse Event profile
2. Local Disease Control Rate (LDCR) at 16 Weeks [ Time Frame: 16 weeks after initiation of FOLFOX chemotherapy ]
   The LDCR at Week 16 will be summarised as a count and proportion of subjects with Local Disease Control at 16 Weeks

Secondary Outcome Measures :

1. Local Progression Free Survival (LPFS), within the pancreas [ Time Frame: From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
   Local Progression Free Survival (LPFS) is defined as the time from enrolment to the date of the radiological scan used to determine local tumour progression or date of death from any cause, whichever comes first.
2. Progression Free Survival [ Time Frame: From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
   Progression free survival (PFS) is defined as the time from enrolment to the date of tumour progression or of recurrence (in case of complete response (CR) or resection of the primary pancreatic tumour), or death from any cause, whichever comes first.
3. Time to symptomatic progression [ Time Frame: From date of enrolment until the date of symptomatic progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
   Time to symptomatic progression is defined as the time between enrolment and worsening of cancer related symptoms as measured by the symptoms domains of QLQ-C30/PAN26
4. Clinical Benefit Response [ Time Frame: From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
   Clinical Benefit Response is a composite endpoint consisting of weight, Performance Status and pain score and will be derived at 4 weekly intervals.The frequency and percentage of subjects with a clinical benefit response will be summarised
5. CA 19-9 response [ Time Frame: From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
   CA 19-19 response will be defined as ≥ 50% decline from baseline and ≥ 90% decline from baseline and return to normal range respectively. Subgroups will be created for study subjects with CA 19-9 > ULN at baseline.
6. Overall Survival [ Time Frame: Through study completion, an average of 18 months ]
   Overall survival (OS) is the time from enrolment to the date of death from any cause.
7. Patient Reported Outcomes [ Time Frame: Through study completion, an average of 18 months ]
   EQ-5D, EORTC QLQ-C30 and PAN26 will be analyses per their validated methodology
8. Pain Scores [ Time Frame: From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
   NRS and QLC-PAN26
9. Weight loss [ Time Frame: From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
   weight will be assessed at all applicable study visits
10. Tumour response [ Time Frame: From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
    RECIST 1.1 per central review
11. Surgical resection rate [ Time Frame: Through study completion, an average of 18 months ]
    assessment of rate of secondary R0/R1 resection
12. Target Tumour Volumetric Change [ Time Frame: From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 7 months after last enrolled patient ]
    A central reading centre will analyse all CT scans to measure target tumour volume changes from baseline.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Histologically or cytologically proven adenocarcinoma of the pancreas.
2. Unresectable locally advanced pancreatic adenocarcinoma according to NCCN 2021 guidelines.Staging and unresectability must be confirmed by central review of the baseline CT scan.
3. Pancreatic target tumour diameter of < 7.0 cm (longest axis), as qualified by the central reading centre.
4. Karnofsky Performance Status ≥ 70
5. ≥ 18 years of age at screening.

6. Considered fit to commence first-line standard FOLFIRINOX chemotherapy:

   i) Adequate renal function: serum creatinine less than 1.5 x upper limit of normal (ULN).

   ii) Adequate liver function: serum liver transaminases ≤ 3 x ULN and serum bilirubin ≤ 1.5 x ULN*.

   *For study participants with recent biliary obstruction treated by drainage (e.g. stent), serum bilirubin of > 1.5 x ULN will be accepted for study entry provided that serial levels demonstrate clear improvement. In addition, chemotherapy should not be commenced until serum bilirubin is ≤ 1.5 x ULN.

   iii) Adequate bone marrow function: white blood cells (WBCs) ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, haemoglobin ≥ 9 g/dL, and platelets ≥ 100,000/mm3 iv) UGT1A1 polymorphism and DPD deficiency test performed and dose reductions applied as per local institutional practice.

7. Provide signed Informed Consent.
8. Willing and able to complete study procedures within the study timelines.
9. Life expectancy of at least 3 months at the time of screening as judged by the investigator.
10. Treated with or eligible to commence prophylactic treatment with a proton-pump inhibitor prior to implantation, and to continue to receive treatment for at least 6 months post implantation.
11. Not pregnant, and if of childbearing potential, agrees to use adequate birth control (hormonal or barrier method of birth control or abstinence) prior to study entry and during the study and agrees not to donate sperm or ova, for the duration of the study and 12 months post implantation of the investigational device.

Exclusion Criteria:

1. Evidence of distant metastases, based on review of baseline CT scan.
2. More than one pancreatic tumour lesion.
3. Any prior radiotherapy or chemotherapy for pancreatic cancer.
4. Pregnant or lactating.

5. In the opinion of the investigator, EUS-directed implantation posing undue study subject risk. This includes:

   i) where previous EUS-FNA was considered technically too difficult to perform; ii) imaging demonstrates multiple collateral vessels surrounding or adjacent to the target tumour within the pancreas; iii) presence (or significant risk) of varices near to the target tumour. Note: The feasibility of implantation of the target tumour and assessment of risk can be repeated at any time between Screening Visit 1 and the implantation date. If any of the above risk features becomes apparent following subject screening and/or enrolment prior to and including at the time of OncoSil™ treatment, the patient should remain in the study but the implantation should be deferred or cancelled.

6. History of malignancy, treated or untreated, within the past five years whether or not there is evidence of local recurrence or metastases, with the exception of basal cell carcinoma of the skin and cervical carcinoma in situ.
7. Evidence of radiographic invasion into stomach or duodenum (if not certain, confirmation must be obtained prior to enrolment).
8. A known history of hypersensitivity to silicon or phosphorous, or any of the OncoSil™ components.
9. Any other health condition that would preclude participation in the study in the judgment of the investigator.

Contacts and Locations

Contacts

Contact: Henk Tissing; +31651384883; henk.tissing@oncosil.com

Contact: Tom Maher; tom.maher@oncosil.com

Locations

Belgium

AZ Maria Middelares; Not yet recruiting

Ghent, Belgium

Contact: Els Monsaert, MD

Italy

San Camillo Forlanini; Not yet recruiting

Rome, Italy

Contact: Carlo Garufi, MD

Contact: Guido Ventroni, MD

Azienda Ospedaliera Universitaria Integrata Verona; Not yet recruiting

Verona, Italy

Contact: Michele Milella, MD

Contact: Giuseppe Malleo, MD

Spain

Hospital Universitari Vall d'Hebron; Not yet recruiting

Barcelona, Spain

Contact: Teresa Macarulla, MD

Hospital General Universitario Gregorio Marañón; Recruiting

Madrid, Spain

Contact: Andrés Muñoz, MD

Hospital Universitario 12 de Octobre; Recruiting

Madrid, Spain

Contact: Rocio Garcia-Carbonero, MD

Hospital Universitario de Fuenlabrada; Recruiting

Madrid, Spain

Contact: Ignacio Juez, MD

Hospital Universitario Ramón y Cajal; Recruiting

Madrid, Spain

Contact: Carmen Guillen Ponce, MD

Clínica Universidad de Navarra; Recruiting

Pamplona, Spain, 31008

Contact: Mariano Ponz Sarvisé, MD

United Kingdom

Imperial College; Not yet recruiting

London, United Kingdom

Contact: Harpreet Wasan, MD

Freeman Hospital; Not yet recruiting

Newcastle Upon Tyne, United Kingdom

Contact: Sanjay Pandanaboyana, MD

University Hospital Southampton; Not yet recruiting

Southampton, United Kingdom

Contact: Ben Maher, MD

Sponsors and Collaborators

OncoSil Medical Limited

Investigators

• Principal Investigator: Michele Milella, MD, PhD; University Hospital of Verona
• Principal Investigator: Giuseppe Malleo, MD, PhD; University Hospital of Verona

More Information

• Responsible Party: OncoSil Medical Limited
• ClinicalTrials.gov Identifier: NCT05466799
• Other Study ID Numbers: ONCO01P04
• First Posted: July 20, 2022
• Last Update Posted: October 23, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD may be shared on an individual basis to study investigators subject to review and approval from the study publication steering committee
• Supporting Materials: Study Protocol; Clinical Study Report (CSR); Analytic Code
• Time Frame: After the release of the primary study publication
• Access Criteria: Request should be made to the chair of the publication steering committee with specification of the proposed analysis and the required IPD

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Oxaliplatin; Irinotecan; Folfirinox; Antineoplastic Agents; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action