Reduced-Dose Chemotherapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Thanh Nga Doan, MD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Disqualifiers: Metastatic disease, Prior chemotherapy, Allergic reactions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

174 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of reduced doses of chemotherapy drugs, docetaxel and cyclophosphamide, for older women with early-stage HER2-negative breast cancer. The goal is to determine if lower doses can effectively combat cancer while minimizing side effects. Participants will be divided into two groups: one receiving reduced doses and the other receiving standard doses, with their experiences compared. Women aged 65 or older with HER2-negative breast cancer, who have not received chemotherapy for their current condition, may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, hormonal therapy should be paused during the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using docetaxel and cyclophosphamide together is safe and effective for treating cancer. In previous studies, patients received docetaxel at a dose of 75 mg/m² and cyclophosphamide at 600 mg/m² every three weeks, and most tolerated this treatment without serious side effects.

The trial available is testing a lower dose of docetaxel with cyclophosphamide. This adjustment is crucial because the full dose can be taxing on the body, particularly for older individuals. By using a smaller dose, the researchers aim to provide a treatment that is gentler on patients while still effectively combating cancer.

Overall, research suggests that this treatment could be a viable option for those who struggle with standard doses. However, it is essential to consult a healthcare provider to determine if it is suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the reduced-dose chemotherapy approach for breast cancer because it aims to minimize side effects while maintaining effectiveness. Unlike standard treatments that use full doses of drugs like docetaxel and cyclophosphamide, this approach reduces the dosage, potentially leading to fewer adverse reactions, which can significantly improve the quality of life for patients. This balance between efficacy and tolerability is what makes this treatment particularly promising compared to traditional chemotherapy options.

What evidence suggests that this trial's treatments could be effective for early stage HER2 negative breast cancer?

Research shows that using docetaxel and cyclophosphamide together can effectively treat certain types of breast cancer. Studies have found that this combination can help some patients live longer. In this trial, participants will join one of two treatment arms: Arm I, where patients receive dose-reduced docetaxel and cyclophosphamide, or Arm II, where patients receive the standard dose of these drugs. By lowering the dose in Arm I, the researchers aim to reduce side effects while still effectively treating the cancer. This approach seeks to maintain treatment effectiveness while improving the quality of life for older women with early-stage HER2-negative breast cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Thanh Nga E Doan, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for older women (65+) with early-stage HER2 negative breast cancer who are vulnerable to chemotherapy toxicity. They must have a CARG-BC score of 6 or higher, be able to consent, and willing to answer questionnaires. Excluded are those who've had chemo for their current breast cancer, have recurrent/metastatic disease, or allergies to similar drugs.

Inclusion Criteria

Ability to provide informed consent or have a legally authorized representative able to consent on behalf of the patient

For patients with bilateral or multifocal/multicentric breast cancers, specific criteria must be met to enroll

My breast cancer is confirmed HER2-negative and has come back or didn't respond to treatment.

Exclusion Criteria

I have been treated with TC for breast cancer before.

I have received chemotherapy for my current breast cancer.

My cancer has returned or spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either dose-reduced or standard dose docetaxel and cyclophosphamide intravenously every 21 days for 4 cycles

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

At least 2 visits per year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Docetaxel

Trial Overview The DOROTHY trial is testing a reduced dose of docetaxel combined with cyclophosphamide in treating older women with stage I-III HER2 negative breast cancer. The aim is to see if this lower dose can effectively treat the cancer while improving quality of life by reducing side effects.

How Is the Trial Designed?

Group I: Arm I: (Dose-reduced docetaxel, cyclophosphamide) Experimental Treatment 4 Interventions

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.

Group II: Arm II: (Standard dose docetaxel, cyclophosphamide) Active Control 4 Interventions

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.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Rising Tide Foundation

Collaborator

Trials

17

Recruited

6,200+

Published Research Related to This Trial

In a trial involving 39 patients with advanced solid tumors, the maximum tolerated doses (MTDs) for docetaxel and cyclophosphamide were determined to be 75 mg/m2 for both drugs, regardless of prior chemotherapy history, indicating a consistent safety threshold.

The most common dose-limiting toxicity was neutropenic fever, occurring in 41% of patients, highlighting the need for careful monitoring and management of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cyclophosphamide in patients with advanced solid tumors. Valero, V.[2018]

In a phase I study involving 45 patients with advanced solid tumors, the combination of docetaxel and cyclophosphamide was found to have a maximum tolerated dose of 700/75 mg/m2 for previously treated patients and 800/75 mg/m2 for untreated patients, with neutropenia being the main dose-limiting toxicity.

The combination therapy showed a promising objective response rate of 69% in 32 patients with metastatic breast cancer, including complete responses in 3 patients, indicating its potential efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination docetaxel/cyclophosphamide in patients with advanced solid tumors. Valero, V.[2018]

Docetaxel has shown high effectiveness as a single-agent treatment for metastatic breast cancer and is currently being tested in phase III trials for combination therapies, indicating its potential as a key player in early breast cancer treatment.

While docetaxel can lead to significant side effects like neutropenia in 91% of patients, strategies such as prophylactic corticosteroids and granulocyte colony-stimulating factors are being explored to manage these toxicities, enhancing its safety profile in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future perspectives of docetaxel (Taxotere) in front-line therapy. Piccart, MJ., Di Leo, A.[2018]

Docetaxel is an effective chemotherapeutic agent for breast cancer treatment, but its use can be limited by various toxicities, including febrile neutropenia and fluid retention.

The review discusses management strategies for these adverse events, aiming to enhance patient quality of life during and after docetaxel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presentation and management of docetaxel-related adverse effects in patients with breast cancer. Ho, MY., Mackey, JR.[2022]

The combination of docetaxel and doxorubicin in treating metastatic breast cancer showed high overall response rates between 57% and 77%, even in patients with challenging prognostic factors, indicating its efficacy as a first-line treatment.

While the combination therapy led to significant hematologic toxicities like neutropenia, these were manageable and did not result in increased rates of serious complications, such as congestive heart failure, compared to single-agent doxorubicin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) plus doxorubicin-based combinations: the evidence of activity in breast cancer. Nabholtz, JM.[2018]

The maximum tolerated dose (MTD) for the combination chemotherapy of docetaxel and cyclophosphamide in patients with advanced breast cancer was determined to be docetaxel 60 mg/m² and cyclophosphamide 400 mg/m², with significant toxicities including neutropenia and leukopenia.

Fifteen patients participated in the study, receiving a total of 33 treatment cycles, highlighting the need for careful monitoring and potential dose adjustments due to the common and severe side effects observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer. Shimizu, T., Enomoto, K., Haga, S., et al.[2019]

Docetaxel is an effective anti-cancer drug with a recommended dosage of 100 mg/m2 every 3 weeks, showing significant activity against breast cancer and non-small cell lung cancer, comparable to established treatments.

The safety profile of docetaxel is well-defined, with major side effects including hypersensitivity reactions, fluid retention, and neutropenia, leading to ongoing phase II trials aimed at reducing these side effects through premedication strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere), a review of preclinical and clinical experience. Part II: Clinical experience. van Oosterom, AT., Schrijvers, D., Schriivers D [corrected to Schrijvers, D].[2019]

In a study of 97 breast cancer patients, those treated with the one-vial ready-to-use formulation (T1V) of Taxotere received a significantly lower dose of the drug compared to those treated with the two-vial preparation (T2V), indicating potential issues with dose delivery.

Patients using the T1V formulation experienced higher rates of cutaneous and neurological toxicities, as well as a greater frequency of grade 3 toxicities, suggesting that the new formulation may have a less favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy. Chanat, C., Delbaldo, C., Denis, J., et al.[2018]

In a pilot phase II study involving 28 patients with metastatic breast cancer, the combination of docetaxel, doxorubicin, and cyclophosphamide showed a high overall response rate of 82%, indicating strong efficacy in treating this condition.

The treatment was associated with significant hematologic toxicity, particularly grade 4 neutropenia in 86% of patients, but there were no severe nonhematologic adverse events or significant cardiotoxicity, suggesting a manageable safety profile when combined with prophylactic antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. Nabholtz, JM., Smylie, M., Mackey, J., et al.[2018]

The combination of docetaxel, doxorubicin, and cyclophosphamide (TAC) shows high efficacy in treating metastatic breast cancer, with response rates reaching up to 80% in preliminary phase II trials.

The TAC regimen is well tolerated, with low rates of cardiac toxicity (only 2% experienced reversible congestive heart failure) despite the high incidence of grade 4 neutropenia in 68% of treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. Nabholtz, JM., Smylie, M., Mackey, JR., et al.[2018]

Citations

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Study Details | NCT06042569 | Dose-Reduced Docetaxel ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7475113/

Four cycles of docetaxel and cyclophosphamide as ... Adjuvant chemotherapy with four cycles of DC in a select population of node negative breast cancer was associated with encouraging long-term survival.

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The effect of reduced RDI of chemotherapy on the outcome ... They found that a CMF dose level < 85% was associated with a significantly worse 10-year disease-free and overall survival only for patients ...

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A Phase I Study of Docetaxel Plus Cyclophosphamide in Solid ... There is little evidence to support the efficacy of cyclophosphamide at doses >600 mg/m2 in patients with breast cancer (26, 27, 28). Therefore, we chose a ...

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Dose-dense adjuvant chemotherapy in node-positive ... Results: Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2376193/

Phase I study of docetaxel in combination with ... The study establishes a recommended dose of docetaxel 75 mg m−2 in combination with cyclophosphamide 600 mg m−2 given every 3 weeks, without the support of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4000576/

Feasibility of four cycles of docetaxel and ... Dose-dense therapies have had a major impact on reducing toxicity and improving outcomes in breast cancer. A combination of docetaxel plus ...

8. withpower.com withpower.com/trial/phase-2-breast-neoplasms-9-2023-2e7b3

Reduced-Dose Chemotherapy for Breast Cancer Research shows that the combination of docetaxel and cyclophosphamide has been effective in treating metastatic breast cancer, with response rates up to 82% in ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820913002553

Original study Feasibility of 4 Cycles of Docetaxel and ... Dose-dense therapies have had a major effect on reducing toxicity and improving outcomes in breast cancer. A combination of TC every 3 weeks has emerged as ...