Clinical trial NCT05585554: Locally Advanced Pancreatic Cancer Treated With ABLAtivE Stereotactic MRI-guided Adaptive Radiation Therapy
Official title: Locally Advanced Pancreatic Cancer Treated With ABLAtivE Stereotactic MRI-guided Adaptive Radiation Therapy (LAP-ABLATE)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pancreatic Cancer
Keywords: Locally Advanced Pancreatic Cancer
SBRT
Radiation Therapy
MRIdian
ViewRay
Lead sponsor: Viewray Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-19
Enrollment: 267
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: Ablative dose magnetic resonance imaging (MRI) guided hypofractionated radiation therapy delivered using daily adaptive dose planning has shown to improve overall survival, relative to patients receiving lower radiation doses, in patients with locally advanced pancreatic cancer, without increasing the rate of serious gastrointestinal toxicity. The next step is to determine how these results compare to chemotherapy alone.

This is a prospective, randomized controlled trial (2:1) comparing induction chemotherapy followed by ablative Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) versus chemotherapy alone in locally advanced pancreatic cancer patients. Overall survival outcomes at 2-years will be evaluated.


Eligibility criteria: Inclusion Criteria:

1. Locally advanced pancreatic adenocarcinoma or adenosquamous carcinoma as defined by NCCN guidelines.
2. Minimum of 4 months interval from chemotherapy start to administration of the last dose/chemo.
3. Minimum 8 cycles of (m)FOLFIRINOX OR 12 doses of gemcitabine/nab - paclitaxel)
4. No radiographic evidence of local or distant disease progression at any time prior to study enrollment after starting chemotherapy
5. At least 18 years of age
6. ECOG performance status ≤ 1
7. Adequate bone marrow and organ function as defined below:

   1. Absolute neutrophil count ≥ 1,000/mcL
   2. Platelets ≥ 75,000/mcL
   3. Hemoglobin ≥ 8.0 g/dL
   4. Total bilirubin ≤ 1.5 x IULN
   5. AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
8. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
9. Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

1. CA19-9 \> 180 U/mL within 30 days of randomization.
2. Any prior abdominal radiation therapy.
3. History of prior malignancy with the exception of: 1) malignancy treated with curative intent and with no known disease for at least 2 years from treatment to study enrollment, 2) adequately treated carcinoma in situ without evidence of disease (i.e. superficial bladder cancer).
4. Currently receiving any other investigational agents.
5. More than one cytotoxic regimen given for pancreatic cancer.
6. Major abdominal surgery within 4 weeks prior to randomization.
7. Definitive surgery for pancreas cancer completed prior to study enrollment (e.g., Whipple procedure).
8. Subject with planned or scheduled definitive surgery for pancreas at time of study enrollment
9. Grade 3 or greater toxicity during induction chemotherapy that has not resolved to at least grade 2
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
11. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
12. Medical/psychological contraindication to having an MRI scan.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 2-years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 2-years
measure: Local Control (LC)
timeFrame: 2-years
measure: Regional Control (RC)
timeFrame: 2-years
measure: Distant Metastasis Free Survival (DMFS)
timeFrame: 2-years
measure: Patient Reported Quality of Life (QoL) using EORTC QLQ-C30 questionnaire
timeFrame: 3-months, 12-months, 24-months
measure: Patient Reported Quality of Life (QoL) using EORTC QLQ-PAN26 questionnaire
timeFrame: 3-months, 12-months, 24-months
measure: Treatment-related toxicity
timeFrame: 90 days
Other outcomes:
Locations:
Study officials:
References:
citation: Rudra S, Jiang N, Rosenberg SA, Olsen JR, Roach MC, Wan L, Portelance L, Mellon EA, Bruynzeel A, Lagerwaard F, Bassetti MF, Parikh PJ, Lee PP. Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Cancer Med. 2019 May;8(5):2123-2132. doi: 10.1002/cam4.2100. Epub 2019 Apr 1.
citation: Eaton AA, Karanicolas P, Johnson MChir CD, Bottomley A, Allen PJ, Gonen M. Psychometric Validation of the EORTC QLQ-PAN26 Pancreatic Cancer Module for Assessing Health Related Quality of Life after Pancreatic Resection. JOP. J Pancreas (Online) 2017; 18(1):19-25.