Dose-Painted Intensity Modulated Radiotherapy Pancreas (DP-IMRT Pancreas)

Phase 1

Recruiting

• Conditions: Pancreatic Adenocarcinoma
• Interventions: Radiation: Dose-Painted Intensity Modulated Radiotherapy

• Registration Number: NCT06024824
• Lead Sponsor: Cancer Trials Ireland

Brief Summary

This is a prospective non-randomised Phase I/II Radiotherapy (RT) study with patients recruited to escalated dose cohorts. Patients with resectable or borderline resectable (per the National Comprehensive Cancer Network (NCCN) criteria) pancreatic adenocarcinoma will receive dose-escalated hypofractionated DP-IMRT via Intensity Modulated Radiotherapy (IMRT) / Volume Modulated Arc Therapy (VMAT).

Detailed Description

The study treatment is radiotherapy. Different doses of radiotherapy will be given to patients. The first group of patients will receive the lowest dose (dose level 1) (this is the dose delivered to patients as standard of care). If the treatment does not cause serious side effects, it will be given to the next group of patients enrolled at a higher dose (dose level 2) (this is called 'dose escalation'). If this higher dose of treatment does not cause serious side effects, the next group of patients will receive a higher dose (dose level 3). The doses will continue to increase for every group of patients, as long as no serious side effects occur. If this happens, the study is halted. Once the optimum dose level has been reached, a larger cohort of patients will all receive this dose.

Phase I: A 3+3 dose escalation design is proposed to determine the maximum tolerated dose (MTD) defined by the number of radiotherapy-related ≥ Grade 3 acute toxicities assessed up to 4 weeks post RT. Three cohorts of between 3 and 6 patients at each dose level will be accrued in order to establish the MTD (minimum of 6, maximum of 18 patients). The MTD defined in Phase I will be the dose which will be used in Phase II of the trial. Phase II: 49 patients: Once the MTD is established, patients will continue to be recruited at that dose level up to a total of 49 patients.

Study Timeline

• Study First Submitted: 2023-06-16
• Study First Submitted QC: 2023-08-29
• Study First Posted: 2023-09-06
• Study Start: 2024-01-30
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-22
• Last Update Posted: 2024-02-23
• Primary Completion: 2027-07
• Study Completion: 2031-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiation; IMRT	Dose-Painted Intensity Modulated Radiotherapy	Fifteen fractions of external beam radiation therapy (EBRT) delivered via IMRT/ VMAT. Cohort 1 (n = 3-6) Single PTV 40.05 Gy/15#, homogenous dose\* Cohort 2 (n = 3-6) High Risk PTV 45 Gy/15# SIB to PTV tumour, Elective PTV 40.05 Gy/15# to nodal regions\* Cohort 3 (n = 3-6) High risk PTV 48 Gy/15# SIB to PTV tumour, Elective PTV 40.05 Gy/15# to nodal regions \* Progression to the next dose in successive cohorts depends on the number of patients experiencing DLTs within 4 weeks post-RT treatment in each patient cohort.

Primary Outcome Measures

Name	Time	Method
Phase 1 - to establish the MTD in a dose-escalated and hypofractionated RT regime delivered via IMRT/VMAT by the number of DLTs	4 weeks	To establish the MTD in a dose-escalated and hypofractionated RT regime delivered via IMRT/VMAT by the number of DLTs, and the rate of patient withdrawal from trial treatment due to DLTs. Analysis will be performed for each cohort after all patients have been assessed for their 4-week post RT assessment.
Phase 2 - to determine the frequency and severity of DLTs due to AE/Toxicity meeting definition of DLT at 4 weeks post RT	4 weeks	The rate of DLTs up to 4 weeks post RT will be calculated. This proportion along with the 90% confidence intervals will be reported.
Phase 2 - to determine the rate of patient withdrawal from trial treatment due to AE/Toxicity meeting definition of DLT at 4 weeks post RT	4 weeks	The rate of withdrawal from trial treatment of patients due to DLTs will be calculated. This proportion along with the 90% Confidence Interval will be reported. Other toxicity data including SAEs will be summarised and presented in tabular format with proportions plus 95% Confidence Interval where appropriate.

Secondary Outcome Measures

Name	Time	Method
To evaluate Quality of Life	2 years	The mean (and standard deviation) of the overall and domain specific European Organisation for Research and Treatment for Cancer (EORTC) Quality Life Questionnaire (QLQ) PAN 26 scores at each time point will be reported (pre-chemotherapy, pre-RT, pre-surgery, 6-, 12- and 24-months post RT).; The EOTRC QLQ PAN 26 questionnaire is a tumour specific quality of life questionnaire for patients with pancreatic cancer.; Minimum value = 0; Max value = 100 Function Scales: Higher numbers mean better function Symptom Scale: Higher numbers mean more symptoms
To document the proportion of peri-operative complications	2 years	The proportion of patients with peri-operative complications will be presented with 95% Confidence Interval.
To quantify the percentage of histologically proven R0 resections in the trial patient group (R0 to be defined as a minimal clearance of at least1 mm).	2 years	The percentage of histologically proven R0 resections in this patient group (R0 to be defined as a minimal clearance of at least 1 mm) will be presented with 95% Confidence Interval.
To determine the rate of failure to progress to surgery due to disease progression during neoadjuvant radiotherapy, and conversely the proportion of patients who do receive surgical resection	2 years	The rate of failure to progress to surgery due to disease progression during neoadjuvant radiotherapy will be presented with 95% Confidence Interval. The rate of progression to surgery will be presented with 95% CI. The proportion of patients who receive surgical resection overall will be presented with 95% Confidence Interval.
To evaluate the impact of treatment on OS, overall and by resectability (whether resectable or borderline resectable)	2 years	The Kaplan-Meier method will be used to estimate OS. This will be expressed as median survival with 95% Confidence Interval and will be analysed after patients have been followed for two years after completion of study treatment. The Log-rank test will be used to compare differences in survival between resectable and borderline resectable patients.
To evaluate the impact of treatment on PFS, overall and by resectability (whether resectable or borderline resectable)	2 years	The Kaplan-Meier method will be used to estimate PFS. This will be expressed as median survival with 95% Confidence Interval and will be analysed after patients have been followed for two years after completion of study treatment. The Log-rank test will be used to compare differences in survival between resectable and borderline resectable patients.
To evaluate tumour response on surgically resected patients using resected specimens	2 years	The proportion of surgically resected patients receiving at least 14 fractions of RT with tumour response using the resected specimens will be presented with 95% Confidence Interval.
To evaluate the incidence of late GI toxicities in patients who do not undergo surgical resection	2 years	The incidence of late toxicity at 6-, 12- and 24-months post-RT, in patients who do not undergo surgical resection, will be calculated, summarised and presented in tabular format with proportions plus 95% Confidence Interval where appropriate. Toxicities of ≥ Grade 2 are of specific interest. Counts and frequencies will be provided for the worst grade AE experienced

Trial Locations

Locations (2)

St Luke's Radiation Oncology Network (SLRON); 🇮🇪 Dublin, Ireland

St Vincent's University Hospital; 🇮🇪 Dublin, Ireland