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: April 11, 2024
• Sponsor: OncoSil Medical Limited
• Information provided by (Responsible Party): OncoSil Medical Limited

Tracking Information

• First Submitted Date: July 12, 2022
• First Posted Date: July 20, 2022
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: April 26, 2023
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2022)

• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 18, 2022)

• 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.
• 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.
• 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
• 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
• 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.
• 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.
• 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
• 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
• 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
• 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
• Surgical resection rate [ Time Frame: Through study completion, an average of 18 months ]
  assessment of rate of secondary R0/R1 resection
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: FOLFIRINOX Versus OncoSil™ in Addition to FOLFIRINOX in Patients With Locally Advanced Pancreatic Adenocarcinoma
• 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.
• 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
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Locally Advanced Pancreatic Cancer

Intervention

• 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

Study Arms

• Active Comparator: FOLFIRINOX Chemotherapy
  Subjects in Arm A will receive up to 12 cycles of Standard Of Care FOLFIRINOX chemotherapy
  Intervention: Drug: FOLFIRINOX chemotherapy
• 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
  Interventions:

  • Drug: FOLFIRINOX chemotherapy
  • Device: OncoSil™

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 18, 2022): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: Australia, Belgium, Italy, Spain, United Kingdom

Administrative Information

• NCT Number: NCT05466799
• Other Study ID Numbers: ONCO01P04
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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

• Current Responsible Party: OncoSil Medical Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: OncoSil Medical Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: OncoSil Medical Limited
• Verification Date: April 2024