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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination of docetaxel and cyclophosphamide 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 some studies. This combination has shown promising results in terms of tumor response, although it can cause side effects like neutropenia (a drop in white blood cells that can lead to infection). ^{1 2 3 4 5}

What safety data exists for reduced-dose chemotherapy using docetaxel and cyclophosphamide in breast cancer treatment?

Docetaxel and cyclophosphamide have been studied for safety in various cancer treatments. Common side effects include neutropenia (low white blood cell count), fluid retention, and skin reactions. Preventive measures like steroids and growth factors can help manage some of these side effects. ^{1 6 7 8 9}

What makes the reduced-dose chemotherapy with Cyclophosphamide and Docetaxel unique for breast cancer?

This treatment is unique because it uses a combination of two drugs, Cyclophosphamide and Docetaxel, at reduced doses to minimize side effects while maintaining effectiveness. The combination is specifically designed to manage toxicity, such as neutropenia (low white blood cell count), which is a common issue with higher doses of chemotherapy. ^{1 2 4 6 10}

Research Team

Thanh Nga E Doan, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Future perspectives of docetaxel (Taxotere) in front-line therapy. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Presentation and management of docetaxel-related adverse effects in patients with breast cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere), a review of preclinical and clinical experience. Part II: Clinical experience. [2019]

9. England 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. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer. [2019]