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A Phase I Dose Escalation Study of Single Fraction Ablative Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer

Primary Purpose

Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Radiomics on MRI
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or tubular) histologies of the breast 3 cm or less(T1-T2cN0) in women who have not undergone surgery or neoadjuvant endocrine or chemotherapy for current breast cancer diagnosis
  2. Tumor must not involve the overlying skin based on imaging evaluation and/or clinical exam
  3. Age >/= 18 years old and female
  4. Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included only if performed BEFORE the biopsy
  5. Tumor must be unifocal
  6. The tumor must be visible on CT scan and/or preferably marked with clip(s) in tumor
  7. Patients must undergo an MRI for work up to aid in tumor delineation and to rule out additional foci of disease. If additional foci of disease are present, they need to have a negative biopsy to proceed with treatment.If patient cannot have MRI, contrast enhanced digital mammography (CEDM) is allowed in place of MRI.
  8. Clinically and radiographically node negative on ultrasound of the axilla or MRI
  9. Estrogen receptor positive or Progesterone receptor positive and Her2neu negative
  10. Ability to understand and the willingness to sign a written informed consent.
  11. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to the start of study and for the duration of radiation therapy. 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, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • 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. Multi-centric disease
  2. Prior RT to the involved breast
  3. Tumor size >3cm
  4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
  5. Patients who are pregnant or lactating due to the potential exposure to the fetus to radiation therapy and unknown effects of radiation therapy to lactating females
  6. Patients unable to have an MRI or contrast enhanced digital mammography (CEDM)
  7. Prior ipsilateral breast cancer
  8. Tumor less than 5mm from the skin surface on clinical exam and/or radiographic imaging
  9. Patients with active Lupus or scleroderma

Sites / Locations

  • University of Texas Southwestern Medical Center - DallasRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single-fraction stereotactic partial breast radiotherapy

Arm Description

The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac,Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer.

Outcomes

Primary Outcome Measures

Reach the maximum tolerated dose (MTD)
The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac, Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer. Done by escalating the dose of SBRT toward the tumorcidal dose of 38 Gy in fraction. Doses will be escalated an additional 3.5-4 Gy per treatment. The phase I portion of the study will be completed when either of the following events occur: 1) the MTD for a cohort is reached or 2) when delivery of a pre-determined highest dose of radiation (38 Gy) that has been deemed likely to be efficacious for treatment of early stage breast cancer is attained.Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.

Secondary Outcome Measures

Cosmesis outcome
Photographs of both breasts will be taken and cosmesis form will be graded by the patient and the radiation oncologist at twelve months from the start of therapy and at yearly intervals thereafter and an independent panel established at UTSW Medical Center will evaluate cosmesis at the end of study. Excellent: When compared to the untreated breast, there is minimal or no difference in the sizes, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance Good: There is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only mild change in the shape Fair: There is obvious difference in the size and shape of the treated breast. This change involves ¼ or less of the breast Poor: Marked change in the appearance of the treated breast involving more than ¼ of breast tissue
Local Control
computed using Kaplan-Meier curves along with the 95% confidence interval
Acute Toxicity
Exact binomial method will be used to calculate toxicity. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Late Toxicity
Exact binomial method will be used to calculate toxicity. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Rates of Surgical Morbidity
Number of patients with surgical morbidity
Pathologic Complete Response Rates
Exact binomial method will be used to calculate the response rate.
Distant Disease-Free Survival
computed using Kaplan-Meier curves along with the 95% confidence interval

Full Information

First Posted
July 25, 2019
Last Updated
October 5, 2023
Sponsor
University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04040569
Brief Title
A Phase I Dose Escalation Study of Single Fraction Ablative Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer
Official Title
A Phase I Dose Escalation Study of Single Fraction Ablative Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 25, 2019 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction.
Detailed Description
Preoperative stereotactic breast radiation may be beneficial as it offers the ability to target smaller treatment volumes than what has been achievable with adjuvant PBI (Nichols IJROBP 2010), track radiobiological response to radiation at time of surgical pathology, and allow the removal of all irradiated tissue to potentially minimize late effects.The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction. This would be accomplished on the CyberKnife or GammaPod. The GammaPod is a novel device dedicated to S-PBI utilizing a Cobalt-60 source (Yu Med Phys 2013), which offers a highly reproducible prone setup with a mean of 1.8mm of mismatch reported in 15 patients at the University of Maryland on consecutive scans (Yu JCO 2011). Implications of this research are far reaching, including determination of the maximally tolerated dose for preoperative S-PBI, pathologic complete response rates of early stage breast cancer to a predicted radioablative dose, radiographic markers of treatment response (radiomics), and translational research assessing mechanisms of immune and radiation response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
All patients in each dose cohort will be treated as a single group for dose escalation. The starting dose for the dose escalation portion will be 30 Gy. Subsequent cohorts of patients will receive an additional 4 Gy per treatment. If significant toxicity is encountered at the starting dose, a de-escalation will occur (step -1) to 26.5 Gy. As we are currently concluding an adjuvant single fraction phase I protocol (ClinicalTrials.gov Identifier: NCT02685332) to 30 Gy in a single fraction for early stage breast cancer, if we meet our endpoints of this study, we will start our dose escalation at 34Gy instead of the 30 Gy, as safety of the 30 Gy arm will have already been established.
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single-fraction stereotactic partial breast radiotherapy
Arm Type
Experimental
Arm Description
The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac,Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer.
Intervention Type
Radiation
Intervention Name(s)
Radiomics on MRI
Intervention Description
Through extracting and analyzing a large number of features from medical imaging, radiomics has shown promising results in treatment outcome prediction for many diseases including breast cancer (45-50). UTSW physics group has developed several new radiomic approaches and radiomic features, such as a multi-objective radiomics model(51) and a new radiomic "Shell" feature(52). As an exploratory end point for this trial, the investigators will explore the application radiomics using pre-treatment MRI, treatment parameters and clinical characteristics as input to predict pathological response of radiation therapy (XRT) based on pathology report of surgical tissues and local recurrence.
Primary Outcome Measure Information:
Title
Reach the maximum tolerated dose (MTD)
Description
The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac, Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer. Done by escalating the dose of SBRT toward the tumorcidal dose of 38 Gy in fraction. Doses will be escalated an additional 3.5-4 Gy per treatment. The phase I portion of the study will be completed when either of the following events occur: 1) the MTD for a cohort is reached or 2) when delivery of a pre-determined highest dose of radiation (38 Gy) that has been deemed likely to be efficacious for treatment of early stage breast cancer is attained.Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Cosmesis outcome
Description
Photographs of both breasts will be taken and cosmesis form will be graded by the patient and the radiation oncologist at twelve months from the start of therapy and at yearly intervals thereafter and an independent panel established at UTSW Medical Center will evaluate cosmesis at the end of study. Excellent: When compared to the untreated breast, there is minimal or no difference in the sizes, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance Good: There is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only mild change in the shape Fair: There is obvious difference in the size and shape of the treated breast. This change involves ¼ or less of the breast Poor: Marked change in the appearance of the treated breast involving more than ¼ of breast tissue
Time Frame
5 years
Title
Local Control
Description
computed using Kaplan-Meier curves along with the 95% confidence interval
Time Frame
5 years
Title
Acute Toxicity
Description
Exact binomial method will be used to calculate toxicity. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Time Frame
90 Days
Title
Late Toxicity
Description
Exact binomial method will be used to calculate toxicity. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Time Frame
24 Months
Title
Rates of Surgical Morbidity
Description
Number of patients with surgical morbidity
Time Frame
5 years
Title
Pathologic Complete Response Rates
Description
Exact binomial method will be used to calculate the response rate.
Time Frame
5 years
Title
Distant Disease-Free Survival
Description
computed using Kaplan-Meier curves along with the 95% confidence interval
Time Frame
5 years

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female only study
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or tubular) histologies of the breast 3 cm or less(T1-T2cN0) in women who have not undergone surgery or neoadjuvant endocrine or chemotherapy for current breast cancer diagnosis Tumor must not involve the overlying skin based on imaging evaluation and/or clinical exam Age >/= 18 years old and female Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included only if performed BEFORE the biopsy Tumor must be unifocal The tumor must be visible on CT scan and/or preferably marked with clip(s) in tumor Patients must undergo an MRI for work up to aid in tumor delineation and to rule out additional foci of disease. If additional foci of disease are present, they need to have a negative biopsy to proceed with treatment.If patient cannot have MRI, contrast enhanced digital mammography (CEDM) is allowed in place of MRI. Clinically and radiographically node negative on ultrasound of the axilla or MRI Estrogen receptor positive or Progesterone receptor positive and Her2neu negative Ability to understand and the willingness to sign a written informed consent. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to the start of study and for the duration of radiation therapy. 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, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or 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: Multi-centric disease Prior RT to the involved breast Tumor size >3cm Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements Patients who are pregnant or lactating due to the potential exposure to the fetus to radiation therapy and unknown effects of radiation therapy to lactating females Patients unable to have an MRI or contrast enhanced digital mammography (CEDM) Prior ipsilateral breast cancer Tumor less than 5mm from the skin surface on clinical exam and/or radiographic imaging Patients with active Lupus or scleroderma
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vanessa Igbeka
Phone
214/648-5779
Email
vanessa.igbeka@utsouthwestern.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Neufeld, MS
Phone
214-645-8525
Email
sarah.hardee@utsouthwestern.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asal Rahimi, MD
Organizational Affiliation
UT Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Southwestern Medical Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Phase I Dose Escalation Study of Single Fraction Ablative Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer

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