Dose-Reduced Docetaxel With Cyclophosphamide for the Treatment of Vulnerable Older Women With Stage I-III HER2 Negative Breast Cancer, the DOROTHY Trial

NCT06042569 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 21374NCI-2023-06506P30CA033572
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 3

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.

Conditions

HER2-Negative Breast Carcinoma; Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Relative dose intensity (RDI)

  RDI is defined as the ratio of actual dose intensity received to the standard dose intensity, ranging from 0 to 100%. The RDI between the two arms will be compared using T-test, RDI difference and 90% confidence interval. A one-sided p-value \< 0.05 will be considered statistically significant.

  At completion of 4 cycles, up to 12 weeks (each cycle is every three weeks)

Secondary Outcomes (11)

• Treatment success

  At completion of 4 cycles, up to 12 weeks (Each cycle is three weeks)

• Patient-reported symptomatic toxicities

  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).

• Differences in PRO-CTCAE and clinician-reported toxicities

  At each chemotherapy cycle for 4 cycles and at 3, 6, 12, and 24 months after treatment ends (Each cycle is three weeks).

• Patient satisfaction

  Up to 3 months after treatment ends

• Changes in function and health status

  At baseline and at 3, 6, 12 and 24 months after treatment ends

Study Arms (2)

Arm I: (Dose-reduced docetaxel, cyclophosphamide)

EXPERIMENTAL

Patients receive dose-reduced 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.

Drug: Cyclophosphamide; Drug: Docetaxel; Other: Medical Chart Review; Other: Questionnaire Administration

Arm II: (Standard dose docetaxel, cyclophosphamide)

ACTIVE COMPARATOR

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.

Drug: Cyclophosphamide; Drug: Docetaxel; Other: Medical Chart Review; Other: Questionnaire Administration

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm I: (Dose-reduced docetaxel, cyclophosphamide); Arm II: (Standard dose docetaxel, cyclophosphamide)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Arm I: (Dose-reduced docetaxel, cyclophosphamide); Arm II: (Standard dose docetaxel, cyclophosphamide)

Medical Chart Review OTHER

Ancillary studies

Also known as: Chart Review

Arm I: (Dose-reduced docetaxel, cyclophosphamide); Arm II: (Standard dose docetaxel, cyclophosphamide)

Questionnaire Administration OTHER

Ancillary studies

Arm I: (Dose-reduced docetaxel, cyclophosphamide); Arm II: (Standard dose docetaxel, cyclophosphamide)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator
• Rising Tide Foundation: collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

MeSH Terms

Interventions

Cyclophosphamide; Docetaxel

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes

Study Officials

• Thanh Nga E Doan, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thanh Nga Doan, MD

CONTACT

626-321-1845; tdoan@coh.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Randomization module also conceals allocation from other study personnel except the biostatistician and the designated study coordinator by limiting their user's right.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 18, 2023
• Study Start: September 16, 2024
• Primary Completion (Estimated): March 20, 2030
• Study Completion (Estimated): March 20, 2030
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (3)