Monitoring Symptoms to Help Young Women Take Hormone Therapy for Stage I-III Breast Cancer, ASPEN Study

• ClinicalTrials.gov Identifier: NCT05568472
• Recruitment Status: Recruiting
• First Posted: October 5, 2022
• Last Update Posted: November 13, 2023
• Sponsor: SWOG Cancer Research Network
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): SWOG Cancer Research Network

Tracking Information

• First Submitted Date: September 23, 2022
• First Posted Date: October 5, 2022
• Last Update Posted Date: November 13, 2023
• Actual Study Start Date: March 29, 2023
• Estimated Primary Completion Date: May 1, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 2022)

Persistence with initially prescribed oral estrogen (ET) medication [ Time Frame: From randomization to discontinuation of the initially prescribed ET for more than 60 days or switching to a new oral ET medication, assessed up to 72 weeks ]

Will be assessed by the treating provider at each study visit every 12 weeks and prospectively documented on the S2010 treatment log, including any switch from the initially prescribed oral ET. Persistence with initially prescribed oral ET by intervention arm out to 72 weeks will be described using Kaplan-Meier plots. Potential differences by arm will be tested using multivariable Cox regression. Persistence with any oral ET (aromatase inhibitor [AI] and/or tamoxifen) at 72 weeks by arm will be examined in a consistent manner. The study stratification variables (age [< 45 vs >= 45], chemotherapy [yes/no], and ET [AI vs tamoxifen]), as well as race, ethnicity, and disease stage, will be included as covariates in the regression models. In the timeframe of evaluation, censored events (newly diagnosed cancer, cancer recurrence, or death) are anticipated to be low.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 4, 2022)

• Occurrence of any non-adherence [ Time Frame: Up to 18 months ]
  Will be assessed using the Voils validated adherence tool that both determines the extent of nonadherence as well as reasons for non-adherence. Kaplan Meier plots will be used to describe patterns of non-adherence between arms. Multivariable Cox regression will be used to assess this secondary endpoint.
• Worst pain [ Time Frame: Up to 12 weeks ]
  Will be measured using the Brief Pain Inventory - Short Form (BPI-SF) "worst pain" question ("Please rate your pain by circling the one number that best describes your pain at its worst in the last 24 hours") in the subset of patients planning to receive AI treatment. Worst pain is measured on an 11-point scale of 0 ("no pain") to 10 ("pain as bad as you can imagine"). Linear regression will be used, adjusting for the stratification factors and the baseline score.
• Incidence of hot flashes [ Time Frame: Up to 12 weeks ]
  Will be assessed using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) "I have hot flashes/hot flushes" (ES1) question in the subset of patients planning to receive tamoxifen therapy. Hot flashes/hot flushes are measured on a scale of 0 ("not at all") to 4 ("very much"), with higher values indicating increased concern over the past 7 days. Linear regression will be used to compare scores between arms, adjusting for the stratification factors and the baseline score.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 4, 2022)

• Symptom bother [ Time Frame: Up to 18 months ]
  Assessed using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) "I am bothered by side effects of treatment" (GP5) question. This is rated on a scale of 0 ("not at all") to 4 ("very much") with higher values indicating worse physical well-being over the past 7 days.
• Symptom burden: average pain [ Time Frame: Up to 18 months ]
  Will be measured using the Brief Pain Inventory - Short Form (BPI-SF) average pain question "Please rate your pain by marking the box beside the number that best describes your pain on the average", range 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine."
• Symptom burden: pain interference [ Time Frame: Up to 18 months ]
  Will be measured using the Brief Pain Inventory - Short Form (BPI-SF) pain interference scale, range 0 to 10, with lower values representing "no interference" and 10 signifying "complete interference."
• Symptom burden: overall health profile [ Time Frame: Up to 18 months ]
  Will be measured using the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) profile subscales: fatigue (33-76), sleep disturbance (32-74), physical function (22-57), depression (41-80), anxiety (40-82), and ability to participate in social roles and activities (27-65). Raw scores (range 4-20 for all subscales) are converted to T scores (approximate ranges shown next to subscale), with mean 50 and standard deviation 10. The T score conversion is handled programmatically by Health Measures and depends upon the number of questions answered, minimums and maximums may differ from those shown here. Higher T scores represent more of the characteristic being measured (e.g., higher T score on fatigue score represents more fatigue, but higher T score on physical function represents better physical function).
• Symptom burden: cognitive function [ Time Frame: Up to 18 months ]
  Will be measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 4a. Raw scores (range 4 to 20) are converted to a T score with mean 50, and standard deviation 10. The approximate minimum and maximum T scores for this scale are 24 and 62 respectively, with higher T scores representing better cognitive function. T score conversion is handled programmatically by Health Measures and depends upon the number of questions answered; actual minimums and maximums may differ depending upon the number of questions answered.
• Symptom burden: endocrine symptoms [ Time Frame: Up to 18 months ]
  Will be measured using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) Endocrine Symptoms Scale. This is a 19-item subscale with range 0 to 76, with higher values representing better quality of life.
• Estradiol concentration [ Time Frame: Up to 18 months ]
  Plasma concentrations of estradiol will be quantitated centrally using a tandem mass spectroscopy-based ultrasensitive estradiol assay
• Adherence to medications based on plasma concentrations [ Time Frame: Up to 18 months ]
  Objectively assessed biochemically by quantitating tamoxifen and AI drug and metabolite plasma concentrations as previously described.
• Genotyping [ Time Frame: Up to 18 months ]
  Germline deoxyribonucleic acid (DNA) will be genotyped by the University of Michigan Advanced Genomics Core using technology available at the time the analysis is performed

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Monitoring Symptoms to Help Young Women Take Hormone Therapy for Stage I-III Breast Cancer, ASPEN Study
• Official Title: A Randomized Phase III Trial Comparing Active Symptom Monitoring Plus Patient Education Versus Patient Education Alone to Improve Persistence With Endocrine Therapy in Young Women With Stage I-III Breast Cancer (ASPEN)
• Brief Summary: This phase III trial compares the effect of active symptom monitoring and patient education to patient education alone in helping young women with stage I-III breast cancer stay on their hormone therapy medicines. The patient education tool contains interactive weblinks which provide patients with education material about breast cancer and side effects of therapy. Symptom monitoring is a weblink via email or text message with questions asking about symptoms. Hormone therapy for breast cancer can cause side effects, and may cause some women to stop treatment early. Asking about symptoms more often may help women keep taking hormone therapy medicines.

Detailed Description

PRIMARY OBJECTIVE:

I. To compare persistence with the initially prescribed oral endocrine therapy (ET) through 72 weeks for young women being treated for hormone-receptor positive stage I-III breast cancer randomized to Active Symptom Monitoring (ASM) + patient education or patient education alone.

SECONDARY OBJECTIVES:

I. To compare patient-reported adherence with the initially prescribed oral ET over time as assessed with the Voils measure between the two arms.

II. To compare worst pain as assessed with the Brief Pain Inventory, in aromatase inhibitors-treated (AI-treated) participants over time between the two arms.

III. To compare hot flashes as assessed with the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) Endocrine Symptoms Scale in tamoxifen-treated participants over time between the two arms.

EXPLORATORY OBJECTIVES:

I. To describe key treatment-emergent symptoms as assessed with the Brief Pain Inventory, the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile, the PROMIS Cognitive Function, and the FACT-ES Endocrine Symptoms Scale over time between the two arms.

II. To develop a composite risk prediction model (including demographics, socioeconomic variables, and clinical variables) to identify participants who are most likely to benefit from ASM.

III. To examine associations between baseline symptom bother as assessed with the GP5 item from the FACT-ES and persistence with oral ET.

IV. To examine the pattern by arm of treatment toxicity from the oral ET agents that are prescribed in this study over time during the first 24 weeks.

V. To compare biochemically determined adherence with the initially prescribed oral ET as assessed with centrally evaluated drug concentrations and metabolites between ASM + patient education and patient education alone over time.

VI. To examine associations overall and by arm between baseline estradiol concentrations evaluated centrally and development of treatment-emergent symptoms as assessed with the Brief Pain Inventory, the PROMIS-29 Profile, the PROMIS Cognitive Function, and the FACT-ES endocrine symptoms scale.

VII. To determine patterns of change overall and by arm in centrally evaluated estradiol concentrations during study participation in participants with chemotherapy-induced ovarian failure, those receiving gonadotrophin releasing hormone (GnRH) agonist therapy, and those who had undergone bilateral salpingo-oophorectomy.

VIII: To identify inherited genetic variants using genome-wide genotyping that contribute to development of endocrine therapy-emergent toxicity.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients are asked 6 brief questions about symptoms weekly by email, text, or phone call for the first 6 months, then every 4 weeks for 12 months. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at baseline, 3, 12, and 18 months.

ARM II: Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at 3, 12, and 18 months.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care

Condition

• Anatomic Stage I Breast Cancer AJCC v8
• Anatomic Stage II Breast Cancer AJCC v8
• Anatomic Stage III Breast Cancer AJCC v8
• Hormone Receptor-Positive Breast Carcinoma

Intervention

• Other: Best Practice
  Standard of care hormone therapy and standard visit with clinician
  Other Names:

  • standard of care
  • standard therapy
• Procedure: Biospecimen Collection
  Undergo correlative studies
  Other Names:

  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
• Procedure: Endocrine Drug Therapy
  Undergo endocrine therapy
• Behavioral: Health Education
  Receive list of websites
• Other: Questionnaire Administration
  Ancillary studies
• Other: Symptom Specific Assessment Tool
  Receive a weblink via email or text message and asked 6 brief questions about symptoms
  Other Names:

  • Symptom Assessment Tool
  • Symptom-Specific Assessment Tool

Study Arms

• Experimental: ARM I (ET, health education, symptom assessment)
  Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients are asked 6 brief questions about symptoms weekly by email, text, or phone call for the first 6 months, then every 4 weeks for 12 months. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at baseline, 3, 12, and 18 months.
  Interventions:

  • Other: Best Practice
  • Procedure: Biospecimen Collection
  • Procedure: Endocrine Drug Therapy
  • Behavioral: Health Education
  • Other: Questionnaire Administration
  • Other: Symptom Specific Assessment Tool
• Active Comparator: ARM II (ET, health education)
  Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at 3, 12, and 18 months.
  Interventions:

  • Other: Best Practice
  • Procedure: Biospecimen Collection
  • Procedure: Endocrine Drug Therapy
  • Behavioral: Health Education
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 4, 2022): 540
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 1, 2028
• Estimated Primary Completion Date: May 1, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must be female and have Stage I, II, or III hormone receptor positive breast cancer based on clinical or pathologic evaluation

• Participants must have been pre- or peri-menopausal at the time of breast cancer diagnosis by satisfying one of the following:

  • had a menstrual period (by self-report) within the 12 months before breast cancer diagnosis, or
  • had a serum or plasma estradiol and/or follicle stimulating hormone (FSH) concentration consistent with premenopausal status (based on institutional standards) within the 12 months before breast cancer diagnosis or when checked after breast cancer diagnosis
• Participants must have started initial treatment with standard of care oral endocrine therapy (ET) (i.e., tamoxifen, anastrozole, exemestane, or letrozole; within 14 days prior to randomization or be planning to start initial treatment with standard of care oral ET within 14 days after randomization
• Participants who currently have ovarian function (estradiol above the postmenopausal range) must be planning to undergo ovarian suppression or ablation concomitantly with oral ET medication, starting before or at the same time as oral ET initiation. Participants with chemotherapy-induced amenorrhea or ovarian failure at time of registration must be planning to start ovarian suppression or ablation if they have recurrence of ovarian function during study participation (circulating estradiol concentration in the premenopausal range or recurrence of menses)
• Participants must have completed surgery for treatment of breast cancer at least 14 days prior to randomization NOTE: Concomitant radiotherapy at the time of randomization and/or during study participation is allowed
• Participants who received chemotherapy must have finished it at least 14 days prior to randomization NOTE: Concomitant maintenance targeted or biologic therapy (e.g., human epidermal growth factor receptor 2 [anti-HER2] therapy, poly-ADP ribose polymerase [PARP] inhibitor therapy, CDK4/6 inhibitor therapy, osteoclast inhibitor therapy) at the time of randomization and/or during study participation is allowed
• Participants must be >= 18 years of age
• Participants must have a complete medical history within 60 days prior to randomization
• Participants must be able to complete Patient-Reported Outcome (PRO) instruments in English or Spanish

Participants must:

• agree to complete PROs at all scheduled assessments and

• complete the pre-registration (baseline) PRO forms within 14 days prior to randomization

  • Participants must be able to complete symptom questions on a web browser (on a smartphone, tablet, or computer) or respond via voice on a telephone in English or Spanish. Participants must agree to complete symptom questions at all scheduled assessments NOTE: Participants who do not have access to the internet and who cannot receive telephone calls for interactive voice response system (IVRS) assessments are not eligible
  • Participants must be offered the opportunity to participate in specimen banking for translational medicine. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) specimen tracking system
  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

Exclusion Criteria:

• Participants must not have distant metastatic breast cancer
• Participants who have started or plan to start treatment with tamoxifen during study participation must not have received prior tamoxifen for treatment or prevention of breast cancer
• Participants who have started or plan to start treatment with an aromatase inhibitor during study participation must not have received prior aromatase inhibitor therapy for treatment or prevention of breast cancer
• Participants must not be taking or planning to take oral estrogen-or progesterone-containing treatments during study participation

NOTES:

• Participants who start or plan to start treatment with an aromatase inhibitor may have previously received tamoxifen for prevention of breast cancer or treatment of a prior cancer
• Participants may have received prior treatment with an aromatase inhibitor for infertility treatment

• Participants must not be planning to become pregnant during the 80 weeks of study participation

  • Participants must not receive additional anti-cancer treatments (i.e., experimental therapy, immunotherapy, biologics, etc.) as part of another clinical trial
  • Participants must not have a non-breast malignancy for which they are currently receiving treatment

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: Peru, United States

Administrative Information

• NCT Number: NCT05568472
• Other Study ID Numbers: S2010; NCI-2022-06902 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S2010 ( Other Identifier: SWOG ); SWOG-S2010 ( Other Identifier: DCP ); S2010 ( Other Identifier: CTEP ); R01CA266012 ( U.S. NIH Grant/Contract ); 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: SWOG Cancer Research Network
• Original Responsible Party: Same as current
• Current Study Sponsor: SWOG Cancer Research Network
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Norah L Henry; SWOG Cancer Research Network

• PRS Account: SWOG Cancer Research Network
• Verification Date: November 2023