Clinical trial NCT06042569: Dose-Reduced Docetaxel With Cyclophosphamide for the Treatment of Vulnerable Older Women With Stage I-III HER2 Negative Breast Cancer, the DOROTHY Trial
Official title: Dose Reduction of Docetaxel-Based Chemotherapy in Vulnerable Older Women With Early-Stage Breast Cancer (DOROTHY)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Anatomic Stage I Breast Cancer AJCC v8
Anatomic Stage II Breast Cancer AJCC v8
Anatomic Stage III Breast Cancer AJCC v8
HER2-Negative Breast Carcinoma
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-09-18
Enrollment: 174
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase II trial tests how well dose-reduced docetaxel combined with cyclophosphamide works in treating older women with early stage (stage I-III) HER2 negative breast cancer vulnerable to toxicity. Chemotherapy drugs, such as docetaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Docetaxel and cyclophosphamide are commonly used, but is not well tolerated at the standard dose and can affect the way older patients feel physically and emotionally. Giving dose-reduced docetaxel combined with cyclophosphamide may be an effective treatment option and improve quality of life in vulnerable older women with stage I-III HER2 negative breast cancer.

Detailed description: PRIMARY OBJECTIVE:

I. Compare the relative dose intensity (RDI) of reduced- versus (vs.) standard-dose docetaxel dosing strategies.

SECONDARY OBJECTIVE:

I. Compare treatment tolerability of reduced- vs. standard-dose docetaxel dosing strategies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive dose-reduced docetaxel intravenously (IV) over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive standard dose docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days then at least twice yearly for 2 years.

Eligibility criteria: Inclusion Criteria:

* Ability to provided informed consent or a legally authorized representative is able to consent on behalf of the patient
* Willing to answer questionnaires as part of their participation
* Age: \>= 65 years by the time of study registration
* Histologically or cytologically confirmed breast cancer(s) that is human epidermal growth factor receptor 2 negative (HER2-negative) per the most recent 2018 American Society of Clinical Oncology College of American Pathologists (ASCO CAP) guidelines relapsed/ refractory disease
* Estrogen receptor and progesterone receptor immunohistochemistry (IHC) status must be known; any estrogen receptor (ER)/progesterone receptor (PR) status is eligible
* Non-metastatic, invasive breast cancer (scans are not required to document non-metastatic disease- any staging work-up is up to the treating providers' discretion)
* Recommended to have either standard dose neoadjuvant docetaxel, cyclophosphamide (TC) chemotherapy or adjuvant TC chemotherapy per their treating provider. Participant may be on immunotherapy concurrently with the protocol regimen at the discretion of the treating physician
* Any surgery, nodal assessment, radiation, hormonal therapy is left up to the treating provider but should not occur concurrently with study therapy
* Any patient who received pre-operative hormonal therapy and who is then recommended for neo/adjuvant chemotherapy is eligible, though hormonal therapy should be held during study treatment administration
* For patients with bilateral or multifocal/multicentric breast cancers, the following criteria must be met to enroll: (1) both cancer are HER2 negative, AND (2) the provider feels the patient will benefit from TC for at least one of the cancers
* Patients who do not speak or read English are eligible as long as adequate interpreter services are available or the surveys are available in the preferred language (i.e. the Geriatric Assessment \[GA\] and Patient Reported Outcomes \[PRO\] surveys are available in many languages)

Exclusion Criteria:

* Participants who have already received any chemotherapy for their current breast cancer
* Patients with recurrent and/or metastatic disease will be excluded. Prior diagnoses of breast cancers (including ductal carcinoma in situ \[DCIS\]) are allowed, provided that the treating provider feels that the current cancer most likely represents a new primary breast cancer and not recurrent disease
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide and/or docetaxel
* Past treatment with the regimen TC for prior breast cancer

Primary outcomes:
measure: Relative dose intensity (RDI)
timeFrame: At completion of 4 cycles, up to 12 weeks (each cycle is every three weeks)
Secondary outcomes:
measure: Treatment success
timeFrame: At completion of 4 cycles, up to 12 weeks (Each cycle is three weeks)
measure: Patient-reported symptomatic toxicities
timeFrame: At each chemotherapy cycle for 4 cycles, end of treatment and at 3, 6, 12 and 24 months after treatment ends)(Each cycle is three weeks).
measure: Differences in PRO-CTCAE and clinician-reported toxicities
timeFrame: At each chemotherapy cycle for 4 cycles and at 3, 6, 12, and 24 months after treatment ends (Each cycle is three weeks).
measure: Patient satisfaction
timeFrame: Up to 3 months after treatment ends
measure: Changes in function and health status
timeFrame: At baseline and at 3, 6, 12 and 24 months after treatment ends
measure: Incidence of adverse events
timeFrame: At every 3 weeks up to completion of study treatment
measure: Invasive disease-free survival
timeFrame: Up to 2 years
measure: Local recurrences
timeFrame: Up to 3 years
measure: Distant recurrences
timeFrame: Up to 2 years
measure: Overall survival
timeFrame: From registration to death due to any cause up to 24 months
measure: Progression-free survival
timeFrame: From registration to the earliest of progression or death due to any cause up to 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: City of Hope Medical Center
name: Thanh Nga E Doan, MD
role: PRINCIPAL_INVESTIGATOR
References: