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

Primary Purpose

Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Docetaxel
Medical Chart Review
Questionnaire Administration
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage I Breast Cancer AJCC v8

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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 Cancer and Aging Research Group- Breast Cancer (CARG-BC) score >= 6 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

Sites / Locations

  • City of Hope Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I: (Dose-reduced docetaxel, cyclophosphamide)

Arm II: (Standard dose docetaxel, cyclophosphamide)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Treatment success
Treatment success is defined as the proportion of patients who receive all 4 planned cycles of chemotherapy without unacceptable toxicity (grade 3-4), hospitalization/death at the end of treatment, and without decline in physical function status. Proportion of treatment success between the 2 arms will be compared using Chi-square test. A one-sided p-value of < 0.05 will be considered statistically significant.
Patient-reported symptomatic toxicities
Toxicities will be described using the National Cancer Institute (NCI) Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patient reported outcomes will evaluate how well symptoms reported correlate/agree with clinician reported adverse events.
Differences in PRO-CTCAE and clinician-reported toxicities
Treatment related toxicities grade 3 or higher experienced by patients between the 2 arms will be described using NCI-CTCAE version (v) 5.0. Chi-square or Fisher exact test will be used to explore the difference in terms of rate of PRO-CTCAE and clinician reported CTCAE between the 2 arms at the end of chemotherapy. Agreement proportions between PRO-CTCAE and clinician reported CTCAE will be explored and calculated for the 2 arms combined.
Patient satisfaction
Patient-reported satisfaction will be measured using the Was It Worth It questionnaire. Data will be scored and summarized according to their scoring manual. Chi-square or Fisher exact test will be used to compare the proportion of patients who consider it worthwhile to undergo treatment, the proportion of patients who would undergo the treatment again, and the proportionof patients who would recommend the treatment to others between the 2 arms.
Changes in function and health status
Elements of the Geriatric Assessment (GA) will be used to calculate the deficit accumulation index for each patient on each study arm over time. Trajectories of change in function will be examined. Data will be scored and summarized according to the GA scoring manual.
Incidence of adverse events
Toxicity experienced by patients for each arm at each cycle will be described using NCI CTCAE v 5.0. Hematologic and non-hematologic toxicities will be examined by grade, type and offending agent.
Invasive disease-free survival
Defined as an occurrence of ipsilateral invasive breast cancer recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, contralateral invasive breast cancer and second non-breast invasive cancer.
Local recurrences
Local recurrence will be defined as the number of in-breast, chest wall after mastectomy and axillary recurrences.
Distant recurrences
Distant recurrence will be defined as the number of recurrences occurring with or without localized recurrence that have occurred distant to the breast.
Overall survival
Breast cancer-specific survival and cause of death will also be examined.
Progression-free survival
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.

Full Information

First Posted
September 7, 2023
Last Updated
September 20, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT06042569
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 14, 2023 (Anticipated)
Primary Completion Date
August 6, 2026 (Anticipated)
Study Completion Date
August 6, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Investigator
Masking Description
Randomization module also conceals allocation from other study personnel except the biostatistician and the designated study coordinator by limiting their user's right.
Allocation
Randomized
Enrollment
174 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I: (Dose-reduced docetaxel, cyclophosphamide)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II: (Standard dose docetaxel, cyclophosphamide)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Docecad, RP56976, Taxotere, Taxotere Injection Concentrate
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Medical Chart Review
Other Intervention Name(s)
Chart Review
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Relative dose intensity (RDI)
Description
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.
Time Frame
At completion of 4 cycles, up to 12 weeks (each cycle is every three weeks)
Secondary Outcome Measure Information:
Title
Treatment success
Description
Treatment success is defined as the proportion of patients who receive all 4 planned cycles of chemotherapy without unacceptable toxicity (grade 3-4), hospitalization/death at the end of treatment, and without decline in physical function status. Proportion of treatment success between the 2 arms will be compared using Chi-square test. A one-sided p-value of < 0.05 will be considered statistically significant.
Time Frame
At completion of 4 cycles, up to 12 weeks (Each cycle is three weeks)
Title
Patient-reported symptomatic toxicities
Description
Toxicities will be described using the National Cancer Institute (NCI) Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patient reported outcomes will evaluate how well symptoms reported correlate/agree with clinician reported adverse events.
Time Frame
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).
Title
Differences in PRO-CTCAE and clinician-reported toxicities
Description
Treatment related toxicities grade 3 or higher experienced by patients between the 2 arms will be described using NCI-CTCAE version (v) 5.0. Chi-square or Fisher exact test will be used to explore the difference in terms of rate of PRO-CTCAE and clinician reported CTCAE between the 2 arms at the end of chemotherapy. Agreement proportions between PRO-CTCAE and clinician reported CTCAE will be explored and calculated for the 2 arms combined.
Time Frame
At each chemotherapy cycle for 4 cycles and at 3, 6, 12, and 24 months after treatment ends (Each cycle is three weeks).
Title
Patient satisfaction
Description
Patient-reported satisfaction will be measured using the Was It Worth It questionnaire. Data will be scored and summarized according to their scoring manual. Chi-square or Fisher exact test will be used to compare the proportion of patients who consider it worthwhile to undergo treatment, the proportion of patients who would undergo the treatment again, and the proportionof patients who would recommend the treatment to others between the 2 arms.
Time Frame
Up to 3 months after treatment ends
Title
Changes in function and health status
Description
Elements of the Geriatric Assessment (GA) will be used to calculate the deficit accumulation index for each patient on each study arm over time. Trajectories of change in function will be examined. Data will be scored and summarized according to the GA scoring manual.
Time Frame
At baseline and at 3, 6, 12 and 24 months after treatment ends
Title
Incidence of adverse events
Description
Toxicity experienced by patients for each arm at each cycle will be described using NCI CTCAE v 5.0. Hematologic and non-hematologic toxicities will be examined by grade, type and offending agent.
Time Frame
At every 3 weeks up to completion of study treatment
Title
Invasive disease-free survival
Description
Defined as an occurrence of ipsilateral invasive breast cancer recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, contralateral invasive breast cancer and second non-breast invasive cancer.
Time Frame
Up to 2 years
Title
Local recurrences
Description
Local recurrence will be defined as the number of in-breast, chest wall after mastectomy and axillary recurrences.
Time Frame
Up to 3 years
Title
Distant recurrences
Description
Distant recurrence will be defined as the number of recurrences occurring with or without localized recurrence that have occurred distant to the breast.
Time Frame
Up to 2 years
Title
Overall survival
Description
Breast cancer-specific survival and cause of death will also be examined.
Time Frame
From registration to death due to any cause up to 24 months
Title
Progression-free survival
Description
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.
Time Frame
From registration to the earliest of progression or death due to any cause up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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 Cancer and Aging Research Group- Breast Cancer (CARG-BC) score >= 6 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanne E Mortimer
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joanne E. Mortimer
Phone
626-256-4673
Email
JMortimer@coh.org
First Name & Middle Initial & Last Name & Degree
Joanne E. Mortimer

12. IPD Sharing Statement

Learn more about this trial

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

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