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S1703 Serum Tumor Marker Directed Disease Monitoring in Patients With Hormone Receptor Positive Her2 Negative Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT03723928
Recruitment Status : Recruiting
First Posted : October 30, 2018
Last Update Posted : May 13, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE October 10, 2018
First Posted Date  ICMJE October 30, 2018
Last Update Posted Date May 13, 2021
Actual Study Start Date  ICMJE July 16, 2018
Estimated Primary Completion Date December 1, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2018)
Assessment of whether patients monitored with STMDDM have non-inferior overall survival compared with patients monitored with usual care [ Time Frame: Up to 312 weeks after randomization ]
The assessment of whether patients monitored with STMDDM have non-inferior overall survival compared with patients monitored with usual care will be based on multivariable Cox regression, adjusting for intervention assignment (intention-to-treat) and the stratification factor (bone only versus visceral disease). If at the time of final analysis the study shows notably fewer events than anticipated, extended follow-up will be examined for its potential to allow examination of the primary endpoint with full power.
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
Overall survival [ Time Frame: Up to 312 weeks after randomization ]
The assessment of whether patients monitored with STMDDM have non-inferior overall survival compared with patients monitored with usual care will be based on multivariable Cox regression, adjusting for intervention assignment (intention-to-treat) and the stratification factor (bone only versus visceral disease). If at the time of final analysis the study shows notably fewer events than anticipated, extended follow-up will be examined for its potential to allow examination of the primary endpoint with full power.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2020)
  • Cumulative direct healthcare costs (in the United States) of patients monitored with STMDDM versus usual care [ Time Frame: Up to 48 weeks after randomization ]
    The comparison of direct healthcare costs (in the US) by arm will be based on a multivariable linear regression, adjusting for patient and tumor characteristics.
  • Assessment of anxiety of patients monitored with STMDDM compared to patients monitored with usual care [ Time Frame: Up to 102 weeks after randomization ]
    Patient anxiety will be measured at baseline and at 12, 24, 36, 48, and 102 after randomization using the State-Trait Anxiety inventory Scale (STAI-S). Differences in anxiety by arm will be evaluated using a mixed-effects model for repeated measures controlling for the baseline score and stratification factor as covariates. No direction of effect will be assumed, implying two-sided testing.
  • Assessment of quality of life of patients monitored with STMDDM versus patients monitored with usual care [ Time Frame: Up to 102 weeks after randomization ]
    Patient quality of life (QOL) will be measured at baseline and at weeks 12, 24, 36, 48, and 102 after randomization using the PROMIS-29. Differences in QOL by arm will be evaluated using a mixed-effects model for repeated measures, controlling for the baseline score and stratification factor as covariates. No direction of effect will be assumed, implying two-sided testing.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
  • Cumulative direct healthcare costs by arm [ Time Frame: Up to 48 weeks after randomization ]
    The comparison of direct healthcare costs by arm will be based on a multivariable linear regression, adjusting for patient and tumor characteristics.
  • Assessment of anxiety by arm [ Time Frame: Up to 102 weeks after randomization ]
    Patient anxiety will be measured at baseline and at 12, 24, 36, 48, and 102 after randomization using the State-Trait Anxiety inventory Scale (STAI-S). Differences in anxiety by arm will be evaluated using a mixed-effects model for repeated measures controlling for the baseline score and stratification factor as covariates. No direction of effect will be assumed, implying two-sided testing.
  • Assessment of quality of life by arm [ Time Frame: Up to 102 weeks after randomization ]
    Patient quality of life (QOL) will be measured at baseline and at weeks 12, 24, 36, 48, and 102 after randomization using the PROMIS-29. Differences in QOL by arm will be evaluated using a mixed-effects model for repeated measures, controlling for the baseline score and stratification factor as covariates. No direction of effect will be assumed, implying two-sided testing.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE S1703 Serum Tumor Marker Directed Disease Monitoring in Patients With Hormone Receptor Positive Her2 Negative Metastatic Breast Cancer
Official Title  ICMJE Randomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored With Serum Tumor Marker Directed Disease Monitoring (STMDDM) Versus Usual Care in Patients With Metastatic Hormone Receptor Positive Breast Cancer
Brief Summary This randomized research trial studies how well serum tumor marker directed disease monitoring works in monitoring patients with hormone receptor positive Her2 negative breast cancer that has spread to other places in the body. Using markers to prompt when scans should be ordered may be as good as the usual approach to monitoring disease.
Detailed Description

PRIMARY OBJECTIVES:

I. To assess whether patients with HER-2 negative, hormone receptor positive, metastatic breast cancer who are monitored with serum tumor marker directed disease monitoring (STMDDM) have non-inferior overall survival compared to patients monitored with usual care.

SECONDARY OBJECTIVES:

I. To compare cumulative direct healthcare costs through 48 weeks among patients monitored with STMDDM versus those monitored with usual care in this patient population.

II. To assess whether the patient-reported outcomes (PROs) of anxiety and quality of life (QOL) are different among patients who are monitored with STMDDM compared with patients who are monitored with usual care in this patient population.

TERTIARY OBJECTIVES:

I. To assess modality and frequency of disease monitoring testing in the usual care cohort.

II. To assess the association of PROs and patient preferences for disease monitoring testing.

III. To evaluate predictors of physician preferences for disease monitoring testing.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients undergo imaging studies at a minimum frequency of every 12 weeks and continue with usual care disease monitoring for up to 312 weeks in the absence of disease progression.

ARM II: Patients undergo disease specific serum tumor marker (STM) evaluation every 4-8 weeks. Patients with elevated STM, undergo imaging evaluation. Patients continue with STMDDM for up to 312 weeks in the absence of disease progression.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Condition  ICMJE
  • Anatomic Stage IV Breast Cancer AJCC v8
  • Estrogen Receptor Positive
  • HER2/Neu Negative
  • Progesterone Receptor Positive
  • Prognostic Stage IV Breast Cancer AJCC v8
  • Elevated CA15-3 or CEA or CA27-29
Intervention  ICMJE
  • Other: Usual care disease monitoring
    Imaging and serum tumor markers are at the discretion of the treating physician (however imaging must be performed at least every 12 weeks).
  • Other: Serum Tumor Marker directed disease monitoring
    Serum tumor markers every 4-8 weeks without imaging
    Other Name: STMDDM
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Anxiety Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE
  • Active Comparator: Arm I (usual care)
    Patients will have imaging studies (modality and frequency per treating physician, however at a minimum frequency of every 12 weeks) alone or in conjunction with STMs (frequency determined by treating physician). Patients will continue with usual care disease monitoring for up to 312 weeks in the absence of disease progression.
    Interventions:
    • Other: Usual care disease monitoring
    • Other: Quality-of-Life Assessment
    • Other: Anxiety Questionnaire Administration
  • Experimental: Arm II (serum tumor directed disease monitoring)
    Patients undergo disease specific serum tumor marker evaluation (CEA and either CA 15-3 or CA 27.29, whichever were tested at Step 1 Registration and Step 2 Registration) every 4-8 weeks (starting from randomization) without imaging until an elevation of at least one disease specific STM. In the event of an elevated STM, the patient will have imaging within 4 weeks to evaluate for disease progression. Patients continue with STMDDM for up to 312 weeks in the absence of disease progression.
    Interventions:
    • Other: Serum Tumor Marker directed disease monitoring
    • Other: Quality-of-Life Assessment
    • Other: Anxiety Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 25, 2018)
1320
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2031
Estimated Primary Completion Date December 1, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • STEP 1 REGISTRATION
  • Patients must have a diagnosis of hormone receptor positive (estrogen receptor positive [ER+] and/or progesterone receptor positive [PR+]), HER-2 negative, metastatic (M1) breast cancer and must be receiving or plan to receive first-line systemic treatment for metastatic disease. (Systemic treatment is any treatment meant to treat the whole body such as endocrine therapy +/- targeted therapy +/- chemotherapy).

    • NOTE: Participants are eligible if they have either de-novo metastatic breast cancer and/or recurrent breast cancer from an earlier stage that is now metastatic
  • Patients must be registered to step 1 between 14 days prior to and 60 days after start of first-line systemic treatment for metastatic disease
  • Patients must have been tested for the following breast cancer specific STMs after diagnosis of metastatic disease and within +/-14 days of initiation of first-line systemic treatment for metastatic disease:

    • CEA (must be tested)
    • CA 15-3 or CA 27.29 (at least one of these must be tested)
    • At least one of the tested STMs must have been >= 2 x the institutional upper limit of normal at this time.

Testing all three STMs is encouraged but only two are required. Patients must plan to have the same two STMs tested for the duration that the patient is on protocol-specified disease monitoring.

  • Patients must have systemic radiographic imaging prior to initiation of systemic therapy or within 30 days of initiation of treatment for metastatic breast cancer and prior to step 1 registration. Modality of imaging is at the discretion of the treating physician.

    • Note: the treating physician can order additional imaging tests at any point prior to randomization at their discretion
  • Patients must be willing to obtain disease monitoring (imaging and/or serum tumor markers) from a consistent facility in which the registering site has access to the results for the duration of the study intervention (312 weeks after step 2 randomization). Imaging and STMs do not need to be completed at the same facility.
  • Patients with known cirrhosis, untreated B12 deficiency, thalassemia, or sickle cell anemia are not eligible as these could cause falsely elevated STM levels
  • Patients with known brain leptomeningeal metastases are not eligible as they may require regular radiographic monitoring to assess treatment response
  • Patients must not be currently enrolled or plan to participate in a first-line treatment trial for metastatic breast cancer with a defined monitoring schedule
  • Patients who are able to complete questionnaires in English or Spanish must participate in patient-reported outcome (PRO) assessments
  • Patients must not be pregnant due to the potential harm to the fetus from radiation exposure from radiographic imaging
  • Except for breast cancer (and previous history of breast cancer), no other prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for five years
  • Patients must not have received prior systemic therapy for metastatic breast cancer, except for their current line of therapy.
  • Patients must have decision making capacity and be able to provide informed consent
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; use of legally-authorized representative is not permissible for this study
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • STEP 2 RANDOMIZATION
  • Patients must be tested for the breast cancer specific STMs that were tested prior to STEP 1 Registration between 56 and 140 days after initiation of first-line systemic therapy for metastatic disease:

    • CEA (must be tested)
    • CA 15-3 or CA 27.29 (whichever was tested prior to Step 1)

Testing all three STMs is encouraged but only two are required. Patients must plan to have the same two STMs tested for the duration that the patient is on protocol-specified disease monitoring.

  • At least one of the STMs that was previously elevated must have decreased from the assessment at step 1 by >= 10% at this time.
  • Patients must not have known progression since registration to step 1
  • Patients must be registered to step 2 randomization between 56 days and 140 days after the initiation of first-line systemic therapy for metastatic disease; This window is inclusive; patients may be registered to Step 2 on day 56 or Day 140. Patients must have been eligible for Step 1 in order to be eligible for Step 2 Randomization
  • Baseline questionnaires must be completed within 28 days prior to step 2 randomization; (Note: Those patients who cannot complete the PRO questionnaires in English or Spanish can be registered to step 2 without contributing to PRO research)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Guam,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03723928
Other Study ID Numbers  ICMJE S1703
NCI-2018-00090 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1703 ( Other Identifier: SWOG )
SWOG-S1703 ( Other Identifier: DCP )
S1703 ( Other Identifier: CTEP )
UG1CA189974 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Melissa Accordino Southwest Oncology Group
PRS Account Southwest Oncology Group
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP