Clinical trial NCT05466799: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Pancreatic Cancer
Lead sponsor: OncoSil Medical Limited
Sponsor class: INDUSTRY
First posted: 2022-07-20
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety and Tolerability
timeFrame: Through study completion, an average of 18 months
measure: Local Disease Control Rate (LDCR) at 16 Weeks
timeFrame: 16 weeks after initiation of FOLFOX chemotherapy
Secondary outcomes:
measure: Local Progression Free Survival (LPFS), within the pancreas
timeFrame: 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
measure: Progression Free Survival
timeFrame: 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
measure: Time to symptomatic progression
timeFrame: 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
measure: Clinical Benefit Response
timeFrame: 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
measure: CA 19-9 response
timeFrame: 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
measure: Overall Survival
timeFrame: Through study completion, an average of 18 months
measure: Patient Reported Outcomes
timeFrame: Through study completion, an average of 18 months
measure: Pain Scores
timeFrame: 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
measure: Weight loss
timeFrame: 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
measure: Tumour response
timeFrame: 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
measure: Surgical resection rate
timeFrame: Through study completion, an average of 18 months
measure: Target Tumour Volumetric Change
timeFrame: 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
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Richmond
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Ghent
country: Belgium
facility: AZ Maria Middelares
city: Rome
country: Italy
facility: San Camillo Forlanini
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octobre
city: Madrid
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Imperial College
city: Manchester
country: United Kingdom
facility: The Christie Hospital/Manchester Royal Infirmary
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
Study officials:
affiliation: University Hospital of Verona
name: Michele Milella, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Verona
name: Giuseppe Malleo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: