ClinicalTrials.gov

History of Changes for Study: NCT04677413
Phase I Trial of Dose-Escalated Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR), for Locally Advanced Rectal Cancer
Latest version (submitted December 28, 2021) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 December 16, 2020 None (earliest Version on record)
2 January 11, 2021 Outcome Measures and Study Status
3 February 11, 2021 Sponsor/Collaborators, Arms and Interventions, Study Status, Outcome Measures, Study Description and Study Identification
4 February 18, 2021 Study Description and Study Status
5 April 14, 2021 Study Status
6 May 4, 2021 Study Status
7 May 19, 2021 Contacts/Locations, Eligibility and Study Status
8 June 3, 2021 Recruitment Status, Study Status, Contacts/Locations and Oversight
9 August 31, 2021 Contacts/Locations and Study Status
10 September 1, 2021 Outcome Measures and Study Status
11 December 28, 2021 Study Description, Study Status, Oversight and Study Identification
Comparison Format:

Scroll up to access the controls

Study NCT04677413
Submitted Date:  January 11, 2021 (v2)

Open or close this module Study Identification
Unique Protocol ID: 2020-1394
Brief Title: Phase I Trial of Dose-Escalated Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR), for Locally Advanced Rectal Cancer
Official Title: Phase I Trial of Dose-Escalated Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR), Chemotherapy and Selective Omission of Surgery for Locally Advanced Rectal Cancer
Secondary IDs:
Open or close this module Study Status
Record Verification: December 2020
Overall Status: Not yet recruiting
Study Start: March 2021
Primary Completion: March 2026 [Anticipated]
Study Completion: March 2026 [Anticipated]
First Submitted: December 16, 2020
First Submitted that
Met QC Criteria:
December 16, 2020
First Posted: December 21, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
January 11, 2021
Last Update Posted: January 14, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University of Texas Southwestern Medical Center
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: We propose a completely new way to deliver a short course type of radiotherapy called, personalized ultra-fractionated stereotactic adaptive radiation (PULSAR). The PULSAR approach will deliver high dose per fraction with a prolonged interval between fractions to allow for maximal response thereby providing the opportunity for adapting subsequent treatments to tumor response
Detailed Description:

PULSAR is a novel radiotherapy treatment paradigm that leverages multiple advantages of high dose per fraction stereotactic treatment techniques with biologic advantages that reduce normal tissue toxicity. There are 4 potential advantages of PULSAR specifically in locally advanced rectal cancer when the goal is to achieve a complete or near complete clinical response permitting omission of surgery:

  1. longer intervals between doses facilitating adaptation of radiotherapy to treatment response. Specifically, each pulse can be replanned to account for volume reduction from prior radiotherapy and chemotherapy, along with changes in the position of mobile normal structures such as bowel and bladder. Therefore, the radiation will be more precise with the goal of improving efficacy as well as decreasing unwanted dose to normal tissues.
  2. longer intervals between doses permitting dose escalation while minimizing injury to normal tissues. In addition to the volumetric changes allowing for optimization of radiotherapy, extended time intervals between each pulse facilitates repair of normal tissues, which is especially critical in situations such as in locally advanced rectal cancer where functional sphincter preservation is a priority. Currently, cumulative radiotherapy dose in rectal cancer is limited by normal tissue toxicity, particularly that of the normal rectum and small bowel. Therefore, temporally spaced fractions allowing for normal tissue repair would also permit increased dose to the primary tumor with the goal of achieve a complete response in a greater proportion of patients.
  3. interdigitation of radiotherapy without interruption of high intensity chemotherapy needed to reduce the risk of metastasis. Multiagent 5-FU based chemotherapy (either FOLFOX or CAPOX) is standard of care in rectal cancer with a trend toward neoadjuvant use in locally advanced cases. Traditionally this is given either before or after radiation therapy often with a several weeks-long break between regimens and never concurrently due to concern for toxicity. On this trial, each pulse of radiotherapy will be given monthly without interruption of chemotherapy. Therefore, all neoadjuvant therapy will be completed over 6 months with no planned breaks.
  4. longer intervals between radiotherapy may alter the systemic effects of radiotherapy. Specifically, daily radiotherapy dosing may hinder generation of adaptive immune responses leading to marked immunosuppression. In contrast, PULSAR may lead to greater adaptive immune responses (akin to creation of a radiotherapy vaccine). Therefore, PULSAR radiotherapy could represent an ideal platform in which to integrate systemic immunotherapy agents in future iterations.

If the regimen is feasible, we believe the results of this study could be highly impactful in the management of rectal cancer.

Open or close this module Conditions
Conditions: Rectal Cancer
Keywords: Rectal Cancer,T3-4 or N+
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Prospective dose evaluation
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 27 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Phase I Dose Cohorts

DOSE LEVEL 1 : 30 Gy (tumor)/ 25 Gy (pelvis)

DOSE LEVEL 2 : 35 Gy (tumor)/ 25 Gy (pelvis)

DOSE LEVEL 3 : 40 Gy (tumor)/ 25 Gy (pelvis)

Radiation: To determine the toxicity of dose-escalated PULSAR RT
To determine the toxicity of dose-escalated PULSAR RT, in patients with locally advanced rectal cancer treated with RT, FOLFOX or CAPOX chemotherapy and selective omission of surgery
Open or close this module Outcome Measures
Primary Outcome Measures:
1. To evaluate the rate of clinical complete and near complete response to radiation and chemotherapy.
[ Time Frame: 1 YEAR ]

Local regrowth will be assessed 1year from completion of treatment and is defined as tumor regrowth in rectum at site of initial tumor.
2. To determine the organ preservation rate a1 yearof PULSAR radiotherapy and FOLFOX or CAPOX chemotherapy.
[ Time Frame: 1 YEAR ]

Acute and late toxicities will be recorded as the rate of treatment related grade 3-5 adverse events experienced in the acute phase from initiation of therapy to 6 weeks treatment to the late phase 6 weeks to 1 year. Proportion of toxicities will be assessed using the NCI's CTCAE v5.0 toxicity criteria
3. To evaluate disease-free survival (DFS), defined as the time between date of therapy completion the first date of docommented disease progression, or death.
[ Time Frame: 1 YEAR ]

quality of life in patients undergoing PULSAR radiotherapy and chemotherapy using the EORTC quality of life questionnaire and Wexner incontinence score.
4. For patients undergoing surgery, to evaluate the rate of R0 resection, defined as a negative surgical margin at time of total mesorectal excision.
[ Time Frame: 1 YEAR ]

R0 resection will be defined by the percent of patients with an R0 resection or negative surgical margin at the time of total mesorectal excision. Acute and late toxicities will be recorded as the rate of treatment related grade 3-5 adverse events experienced in the acute phase from initiation of therapy to 6 weeks treatment to the late phase 6 weeks to1 year, using the NCI's CTCAE v5.0 toxicity criteria
5. To evaluate the rate of distant failure, defined as development of disease outside of the pelvis
[ Time Frame: 1 YEAR ]

The rate of distant failure will be recurrence of disease outside of the pelvis that will be collected on time interval since completion of therapy and be evaluated as a median or rate up to 1-year follow-up. Time will be backdated to when the recurrence was observed
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
  2. Willing and able to provide written informed consent
  3. Pathologic diagnosis of rectal adenocarcinoma
  4. T3-4 and/or N+ disease
  5. No prior treatment for rectal adenocarcinoma
  6. Eastern Cooperative Group (ECOG) performance status of 0-2.
  7. Laboratory values supporting acceptable organ and marrow function within 30 days of eligibility confirmation. Defined as follows:
    • WBC ≥ 3,000/mL;
    • ANC WBC ≥ 1,500/mL;
    • PLT ≥ 75,000/mL;
    • T Bili ≤ 1.5 x upper limit of normal (ULN);
    • AST/ALT ≤ 2.5 x ULN;
    • Creatinine not above ULN, or creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  8. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of study therapy through 90 days after the last dose of study drugs. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

8.1 Has not undergone a hysterectomy or bilateral oophorectomy; or 8.2 Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Exclusion Criteria:

  1. Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT or PET
  2. Prior RT to the pelvis.
  3. Uncontrolled comorbid illness or condition including an infection, congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
  4. Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
  5. Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Open or close this module Contacts/Locations
Central Contact Person: Sandra Morones
Telephone: 2146458525
Email: Sandra.Morones@UTSouthwestern.edu
Central Contact Backup: sarah Hardee
Telephone: 12146458525
Email: sarah.hardee@utsouthwestern.edu
Study Officials: Nina Sanford, MD
Principal Investigator
UT SOUTHWESTERN medical CENTRE
Locations: United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390-8849
Contact:Contact: sarah Hardee 214-645-8525 sarah.neufeld@UTSouthwestern.edu
Contact:Principal Investigator: Nina Sanford, M.D.
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services