NCT02950025

Brief Summary

In light of this new technology and preliminary findings of low toxicity of online, adaptive, magnetic resonance (M)-guided stereotactic radiation on a single arm prospective study, the investigators propose to compare this technique to online MR-guided stereotactic body radiation therapy (SBRT) without adaptation. Online plan adaptation increases treatment times for patients and comprises an increased burden on technical and clinical staff. Although preliminary trial results are encouraging, it remains unclear if the dosimetric benefits of online-adaptive planning studies will translate to measurable improvements in clinical outcomes that merit its routine use. In our preliminary study, plan adaptation was most often required when tumors were adjacent to the gastrointestinal tract (the esophagus to the sigmoid colon), as those structures were most commonly the dose-limiting structures and were noted to change in location on a day-to-day basis. For these reasons, abdominal disease sites have historically highlighted the limitations of SBRT. Specifically, the investigators will enroll patients with oligometastatic or unresectable primary disease of the non-liver abdomen to a randomized, prospective trial. Patients will be randomized to one of two treatment arms, in which they will receive either online-adaptive, MRI-guided SBRT or non-adaptive MRI-guided SBRT. Both patient groups will undergo MRI simulation and MRI treatment localization with online MR monitoring and/or gating. All patients will be treated in five fractions over one to two weeks. By adhering to strict normal tissue constraints, the investigators expect toxicity to be within the current standard of care for the non-adaptive arm, with reduction in toxicity in the arm of patients who undergo adaptation based on daily anatomic changes.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_2 pancreatic-cancer

Timeline
Completed

Started Jan 2017

Shorter than P25 for phase_2 pancreatic-cancer

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 27, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 31, 2016

Completed
3 months until next milestone

Study Start

First participant enrolled

January 19, 2017

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 19, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 19, 2018

Completed
1 year until next milestone

Results Posted

Study results publicly available

March 20, 2019

Completed
Last Updated

April 3, 2019

Status Verified

March 1, 2019

Enrollment Period

1.2 years

First QC Date

October 27, 2016

Results QC Date

February 26, 2019

Last Update Submit

March 26, 2019

Conditions

Outcome Measures

Primary Outcomes (1)

  • Number of Grade 3 or Greater Toxicity Occurring in Patients Receiving Online, Adaptive, MRI-guided SBRT to the Abdomen and in Patients Receiving Non-adaptive SBRT

    * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. * Grade 3 or higher toxicities that did not predate SBRT and are probably or definitely attributable to treatment * Please note that the following statistical analysis was not performed due to small sample size: Statistical analysis will be powered to detect a reduction of toxicity from 35% Grade 3 or greater toxicity to 10% Grade 3 or greater toxicity using online-adaptive therapy. Statistical analysis will be one-sided test for independent proportions.

    Up through 6 months post-treatment (approximately 6 months and 2 weeks)

Secondary Outcomes (6)

  • Tumor Response Rate

    At six month follow-up (approximately 6 months and 2 weeks)

  • Progression-free Survival (PFS) Rate

    At six month follow-up (approximately 6 months and 2 weeks)-up

  • Disease Free Survival Rate

    At six month follow-up (approximately 6 months and 2 weeks)

  • Overall Survival (OS) Rate

    At six month follow-up (approximately 6 months and 2 weeks)

  • Patient Reported Overall Quality of Life During the Past Week as Measured by EORTC QLQ-C30 Quality of Life

    Pre-treatment, six-weeks post treatment, and six months post-treatment

  • +1 more secondary outcomes

Study Arms (2)

Online non-adaptive MRI-guided SBRT

ACTIVE COMPARATOR

* All patients will be initially planned for stereotactic body radiation therapy to a minimum dose of 50Gy in five fractions to the planning target volume (PTV) * Radiotherapy will consist of stereotactic body therapy, to be given over five fractions, delivered once daily or once every other day for a period of one to two weeks, for a total of five treatments * All patients will undergo both CT and MRI simulation in positioning appropriate for the specific treatment site * Quality of life questionnaire baseline, 6 weeks after treatment conclusion, and 6 months after treatment conclusion

Device: Online, non-adaptive MR-guided SBRTOther: European Organization for Research and Treatment of Cancer (EORTC) QLQ-30

Arm B: Online-Adaptive MRI-guided SBRT

EXPERIMENTAL

* All patients will be initially planned for stereotactic body radiation therapy to a minimum dose of 50Gy in five fractions to the planning target volume (PTV) * Radiotherapy will consist of stereotactic body therapy, to be given over five fractions, delivered once daily or once every other day for a period of one to two weeks, for a total of five treatments * All patients will undergo both CT and MRI simulation in positioning appropriate for the specific treatment site * When patients present for their first SBRT treatment session, the treating physician will evaluate their individual anatomy to determine if adaptive planning is indicated. Patients randomized to the online-adaptive treatment planning arm will have all tumor volumes and critical structures within 3 axial slices of the PTV re-contoured on the MR-localization image of the day * Quality of life questionnaire baseline, 6 weeks after treatment conclusion, and 6 months after treatment conclusion

Device: Online, adaptive MR-guided SBRTOther: European Organization for Research and Treatment of Cancer (EORTC) QLQ-30

Interventions

Patients randomized to the online-adaptive treatment planning arm will have all tumor volumes and critical structures within 3 axial slices of the PTV re-contoured on the MR-localization image of the day. The estimated delivered dose should be calculated using the software on the console. An adapted radiation therapy plan should be generated

Arm B: Online-Adaptive MRI-guided SBRT

Patients will not have online-adaptive treatment planning

Online non-adaptive MRI-guided SBRT

* 30 questions * 28 questions about various health issues with answers ranging from 1=Not At All to 4 = Very Much * 1 question asking about overall health with answers ranging from 1=very poor to 7 excellent * 1 question asking about overall quality of life with answers ranging from 1=very poor to 7=excellent

Also known as: EORTC QLQ-30
Arm B: Online-Adaptive MRI-guided SBRTOnline non-adaptive MRI-guided SBRT

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Oligometastatic disease or unresectable primary abdominal malignancy with biopsy-proven primary disease histology of solid tumor categorization. Patients with a diagnosis of hepatocellular carcinoma do not require a biopsy.
  • No more than three progressive sites of disease, with at least one of the disease sites to be deemed suitable for treatment with MRI-guided, online adaptive SBRT to the non-liver abdomen as per radiation oncology evaluation.
  • Must be treated per protocol to lesion(s) of a single abdominal site that can reasonably be encompassed within a single treatment field. Treatment of additional site(s) outside of the abdomen while the patient is on trial is acceptable.
  • The treated lesion must be within 2 cm of the abdominal gastrointestinal tract (abdominal esophagus to sigmoid colon) on the basis of cross sectional imaging study such as computed tomography (CT), positron emission tomography (PET)/CT, or MRI.
  • Must be deemed medically fit for SBRT by the treating physician.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Must have completed any systemic therapy at least one week prior to planned start of SBRT (two weeks preferred), and must have no plans to initiate systemic therapy for at least one week following end of SBRT (two weeks preferred).
  • 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.
  • Able to understand and willing to sign an Institutional Review Board (IRB) approved, written informed consent document (or that of legally authorized representative, if applicable).

You may not qualify if:

  • Primary disease of hematologic origin, lymphoma, or small cell cancer.
  • Past history of external beam radiotherapy within the projected treatment field of any of the disease sites to be treated by MRI-guided, online adaptive SBRT.
  • Currently receiving any other investigational agents.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry.
  • Medical contraindication to undergoing MR imaging.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

MeSH Terms

Conditions

Pancreatic NeoplasmsCarcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeLiver NeoplasmsLiver Diseases

Limitations and Caveats

Please note that the Principal Investigator (PI) changed for the study after all patients were off follow-up and the protocol title page didn't change at that time. This is why the listed PI is different than the PI on the title page of protocol.

Results Point of Contact

Title
Michael C. Roach, M.D.
Organization
Washington University School of Medicine

Study Officials

  • Michael C Roach, M.D.

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 27, 2016

First Posted

October 31, 2016

Study Start

January 19, 2017

Primary Completion

March 19, 2018

Study Completion

March 19, 2018

Last Updated

April 3, 2019

Results First Posted

March 20, 2019

Record last verified: 2019-03

Data Sharing

IPD Sharing
Will not share

Locations