Chemotherapy + Stem Cell Transplant for Breast Cancer

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Disqualifiers: Age over 60, Heart disease, 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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining chemotherapy and stem cell transplants for treating stage IIIB breast cancer. The researchers aim to determine if stem cells can help patients tolerate higher chemotherapy doses, potentially killing more cancer cells. Participants are divided into two groups: one group receives multiple chemotherapy cycles before surgery, while the other receives one cycle before surgery, followed by high-dose chemotherapy and stem cell transplants. The trial seeks patients diagnosed with stage IIIB breast cancer within the last six months, particularly those with skin symptoms like redness or swelling. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention limits on previous chemotherapy, so it's best to discuss your current medications with the trial team.

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

Research has shown that the treatments under study—cisplatin, cyclophosphamide, doxorubicin hydrochloride, melphalan, and paclitaxel—have safety information from other studies.

Cisplatin effectively treats advanced cancers but can affect both healthy and cancer cells, leading to side effects. Cyclophosphamide may cause serious side effects, yet it generally yields positive results in breast cancer treatment. Doxorubicin hydrochloride is commonly used for breast cancer, though high doses can increase the risk of heart problems.

Melphalan is generally tolerable for some cancer treatments but is classified as a carcinogen, meaning it could potentially cause cancer. Paclitaxel effectively controls tumors and is considered safe when administered in certain doses.

This trial is in Phase 2, focusing on the treatment's efficacy and safety in a larger group. The treatment remains under study, so the safety data is not final, but it builds on previous research showing how these drugs have performed in similar situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with a stem cell transplant for breast cancer because it offers a unique approach that could enhance treatment effectiveness. Unlike standard treatments, which might include surgery, radiation, and conventional chemotherapy alone, this approach involves high-dose chemotherapy followed by the return of the patient's own bone marrow cells. This method aims to allow for more intensive chemotherapy by using stem cells to help the body recover faster. Additionally, the protocol includes personalized follow-up treatments, such as radiation and extended tamoxifen therapy, which may improve long-term outcomes by targeting residual cancer cells. This comprehensive strategy could potentially offer better survival rates and quality of life for patients.

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

Research has shown that certain chemotherapy drugs effectively treat breast cancer. For example, cisplatin, a platinum-based drug, improves treatment outcomes, such as tumor response. Cyclophosphamide, when combined with other drugs, has extended patient survival. Doxorubicin is known for its potent ability to kill cancer cells, often outperforming drugs like paclitaxel in advanced cases. High doses of melphalan have been linked to complete tumor shrinkage. Paclitaxel effectively treats metastatic breast cancer, and patients generally tolerate it well. In this trial, participants will receive these chemotherapy drugs in different treatment arms, with either one cycle or more than one cycle of neoadjuvant chemotherapy, followed by stem cell transplantation. These approaches may enhance the effectiveness of treatments for stage IIIB breast cancer. ^{5 6 7 8 9}

Who Is on the Research Team?

George Somlo, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals under 60 with stage IIIB breast cancer showing skin invasion or inflammation symptoms. They must have good heart and lung function, no severe psychosocial issues, and cannot be pregnant. Those with a history of other cancers in the last 5 years (except certain skin or cervical cancers) can't join.

Inclusion Criteria

Your liver enzymes (SGOT or SGPT) should not be more than 1.5 times the normal limit.

Your lung function test shows that your lungs are working at least 60% as well as they should be.

You do not have hepatitis B or HIV.

Exclusion Criteria

You have had a type of disease that affects your lymphatic system.

You have had cancer that is currently active.

You had cancer in the last 5 years, except for certain types of skin cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive doxorubicin and paclitaxel with filgrastim support, followed by modified radical mastectomy

10-12 weeks

Multiple visits for chemotherapy administration

High-dose Chemotherapy and Stem Cell Rescue

Participants undergo two courses of high-dose chemotherapy with stem cell rescue

8-12 weeks

Inpatient stays for chemotherapy and stem cell infusion

Radiation Therapy

Radiation therapy is administered following high-dose chemotherapy

4-7 weeks

Hormone Therapy

Tamoxifen is administered to patients with hormone receptor positive tumors

5 years

Follow-up

Participants are monitored for relapse and survival

5 years

Every 3 months for 2 years, then annually for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bone Marrow Ablation with Stem Cell Support
• Cisplatin
• Conventional Surgery
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Filgrastim
• Melphalan
• Paclitaxel
• Peripheral Blood Stem Cell Transplantation

Trial Overview The study tests high-dose chemotherapy combined with stem cell transplantation to treat advanced breast cancer. It aims to see if this approach is more effective at killing tumor cells than standard treatments.

How Is the Trial Designed?

Group I: More than 1 cycle of neoadjuvant chemotherapy Experimental Treatment 9 Interventions

Patients receive chemotherapy, followed by two treatment cycles of very high-dose chemotherapy, return of bone marrow derived cells, followed by radiation therapy and if indicated five years of tamoxifen treatment.

Group II: 1 cycle of neoadjuvant chemotherapy Experimental Treatment 11 Interventions

Patients receive chemotherapy, surgical removal of the cancer followed by additional chemotherapy, followed by two treatment cycles of very high-dose chemotherapy, return of bone marrow derived cells, followed by radiation therapy and if indicated five years of tamoxifen treatment.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

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+

Published Research Related to This Trial

In a Phase II study involving 46 patients with metastatic breast cancer, the combination of carboplatin and etoposide showed a 42% objective response rate in patients who had not received prior chemotherapy, indicating its potential effectiveness as a treatment option.

However, the combination was ineffective in patients who had previously undergone chemotherapy for metastatic cancer, suggesting it may not be suitable for salvage therapy in those cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of carboplatin and etoposide in metastatic breast cancer. Crown, J., Hakes, T., Reichman, B., et al.[2019]

Cytotoxic chemotherapy remains a key treatment for metastatic breast cancer (MBC), with options like re-challenge with anthracyclines or taxanes, capecitabine, and newer agents like etirinotecan pegol showing promising results in phase II studies.

Etirinotecan pegol, a novel cytotoxic agent, is being further evaluated in the phase III BEACON trial, highlighting the ongoing search for effective treatments that target new pathways and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic chemotherapy: Still the mainstay of clinical practice for all subtypes metastatic breast cancer. Twelves, C., Jove, M., Gombos, A., et al.[2022]

Taxol, when administered intravenously, has a well-established safety profile based on data from 655 patients, with myelosuppression, particularly neutropenia, identified as the main dose-limiting toxicity, which was less severe with a 3-hour infusion schedule.

Severe hypersensitivity reactions were effectively managed with a premedication regimen, and while mild to moderate peripheral neuropathy was observed, it rarely led to treatment discontinuation, indicating a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Taxol safety. Onetto, N., Canetta, R., Winograd, B., et al.[2015]

Paclitaxel and docetaxel are effective antineoplastic drugs that work by promoting microtubule assembly and inhibiting disassembly, showing clinical activity against ovarian, breast, and bronchial cancers.

Both drugs can cause dose-limiting neutropenia and other side effects like myalgias and alopecia, but premedications have been effective in reducing hypersensitivity reactions, allowing for safer administration in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The taxoids: paclitaxel (Taxol) and docetaxel (Taxotere). Pazdur, R., Kudelka, AP., Kavanagh, JJ., et al.[2019]

A randomized trial by the Eastern Cooperative Oncology Group (ECOG) is comparing the effectiveness of single-agent doxorubicin, single-agent paclitaxel, and their combination in treating metastatic breast cancer, with initial results currently being analyzed.

ECOG is also exploring ways to reduce the cardiac toxicity associated with doxorubicin by adding dexrazoxane, while ongoing trials are investigating the combination of carboplatin and paclitaxel to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel doublets in metastatic breast cancer: Eastern Cooperative Oncology Group and Hoosier Oncology Group Studies. Sledge, GW.[2015]

Paclitaxel (Taxol) is an effective chemotherapy agent for treating ovarian cancer and metastatic breast cancer, particularly in patients who have not responded to platinum-based treatments.

Nurses must be aware of the potential side effects of Paclitaxel, such as hypersensitivity reactions and peripheral neuropathy, and follow specific administration guidelines to avoid complications related to its interaction with PVC intravenous-giving sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. Preston, NJ.[2019]

A large meta-analysis involving over 2,000 patients showed that carboplatin is as effective as cisplatin for treating advanced ovarian cancer, but with significantly less toxicity, making it a safer option for patients.

The combination of carboplatin and cyclophosphamide is recognized as an effective therapy, and ongoing clinical trials are exploring various regimens to optimize treatment strategies for advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin versus cisplatin in ovarian cancer. Alberts, DS.[2015]

In two ongoing dose-finding studies involving 33 patients with advanced non-small cell lung cancer (NSCLC) and 11 with advanced ovarian cancer, the combination of paclitaxel and carboplatin is being tested to determine optimal dosing, with paclitaxel administered as a 3-hour infusion.

The most common side effect observed was neutropenia, but it did not lead to any infections, indicating a manageable safety profile; other side effects included hair loss and mild nausea, with no significant differences in toxicity based on the order of drug administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of two dose-finding studies of paclitaxel (Taxol) and carboplatin in non-small cell lung and ovarian cancers: a European Cancer Centre effort. Giaccone, G., Huizing, M., ten Bokkel Huinink, W., et al.[2015]

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