Chemotherapy Response Prediction for Breast Cancer

(RESPONSE Trial)

Recruiting at 2 trial locations

Overseen By Maria Rodriguez

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor Breast Care Center

Must not be taking: Anti-anginals, Pacemaker meds

Disqualifiers: Stage IV, Inflammatory breast cancer, Pregnant, Cardiac disease, HIV, 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: 8

185 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the shrinkage of breast cancer tumors during chemotherapy can predict the amount of cancer remaining after surgery. It includes treatments such as Carboplatin, Cyclophosphamide, Doxorubicin, Paclitaxel, Pertuzumab, and Trastuzumab, tailored to the specific type of breast cancer. Individuals with tumors larger than 2 cm who have triple-negative, HER2-positive, or high-risk estrogen receptor-positive breast cancer may be suitable candidates. The goal is to enhance understanding of tumor response to treatment, potentially improving future breast cancer care. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to advancements in breast 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, if you are on treatments for breast cancer or have a history of cardiac disease, you may need to discuss this with the trial team.

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

Research shows that each treatment in this trial has been studied for safety in people with breast cancer.

**Paclitaxel** is generally well-tolerated for different types of breast cancer. Studies on Triple Negative Breast Cancer (TNBC) have preferred it due to manageable side effects. For HER2-Positive and Hormone Receptor Positive breast cancers, it proved effective without causing major heart problems.

**Carboplatin** has a manageable safety profile in TNBC, improving outcomes without severe harm. It is safe for Hormone Receptor Positive breast cancer when used as part of therapy.

**Doxorubicin** is a well-known treatment for various breast cancers, including TNBC and HER2-Positive. It is effective, though some studies note potential heart issues as a side effect.

**Cyclophosphamide** is used with other treatments and works well for TNBC and HER2-Positive cancers, though it may slightly increase the risk of other cancers over time.

**Trastuzumab** is commonly used for HER2-Positive breast cancer and is generally safe, though it can cause heart problems.

**Pertuzumab** is also used for HER2-Positive breast cancer and is mostly safe, but it can lead to diarrhea and fatigue.

Overall, these treatments are widely used and have a history of being effective and reasonably safe in clinical settings. Always discuss potential side effects with healthcare professionals to know what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they combine standard chemotherapy drugs with additional targeted therapies like pembrolizumab, trastuzumab, and pertuzumab. Unlike typical chemotherapy that attacks rapidly dividing cells in general, pembrolizumab is an immunotherapy that helps the immune system specifically target cancer cells. Trastuzumab and pertuzumab are monoclonal antibodies designed to target the HER2 protein, which can promote the growth of cancer cells. By integrating these targeted approaches, the treatments aim to enhance effectiveness and potentially reduce side effects compared to standard chemotherapy alone. This innovative combination holds promise for improving outcomes in various types of breast cancer, including triple-negative and HER2-positive cases.

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

Research has shown that the chemotherapy drugs used in this trial effectively combat breast cancer in various situations. Participants with Triple Negative Breast Cancer (TNBC) and tumors larger than 5 cm will receive a regimen including paclitaxel and carboplatin. Studies have found this combination improves cancer response and increases survival rates. Paclitaxel is effective for advanced TNBC, and when combined with carboplatin, it enhances treatment success.

For participants with HER2-Positive Breast Cancer, the trial includes trastuzumab and pertuzumab, which have been proven to greatly reduce the chance of cancer recurrence and improve survival rates. Trastuzumab, in particular, is linked to a significant decrease in cancer recurrence and death. When used with trastuzumab, pertuzumab significantly extends the lives of patients with HER2-positive cancer.

In the Hormone Receptor Positive Breast Cancer arm, cyclophosphamide is used with other treatments, showing benefits in improving patient response and increasing survival rates. Overall, these drugs have proven effective for different types of breast cancer, with strong evidence supporting their use in improving patient outcomes. ^{1 4 5 6 7}

Who Is on the Research Team?

Mothaffar Rimawi, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with invasive breast cancer that's at least 2 cm large, including triple negative, HER2-positive, or high-risk estrogen receptor positive types. Participants must be able to consent and use non-hormonal contraception if applicable. They should have good organ function and heart health but no severe diseases, HIV/hepatitis infections, recent other cancers, psychiatric issues preventing study compliance, prior breast cancer treatments or surgeries.

Inclusion Criteria

Left ventricular ejection fraction (LVEF) ≥ the institutional lower limit of normal

Participation in a concurrent clinical trial is permitted, with Principal Investigator approval

My breast cancer is confirmed and may be triple negative, HER2-positive, or high-risk estrogen receptor positive.

Exclusion Criteria

Participants who are pregnant or lactating

I don't have any health conditions that would stop me from receiving or following up on treatment.

My condition is confirmed to be at Stage IV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive chemotherapy prior to surgery, including Paclitaxel and other drugs depending on the breast cancer subtype

16 weeks

8 cycles of treatment

Surgery

Surgical procedure to assess pathologic response and remove any remaining tumor

1 week

Follow-up

Participants are monitored for safety and effectiveness after surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cyclophosphamide
• Doxorubicin
• Paclitaxel
• Pembrolizumab
• Pertuzumab
• Pertuzumab/Trastuzumab/Hyaluronidase-zzxf
• Trastuzumab

Trial Overview The study tests whether the shrinkage of a tumor from chemotherapy before surgery can predict how much tumor remains at surgery time. It involves drugs like Carboplatin and Trastuzumab among others in patients with early-stage breast cancer to see if physical changes correlate with surgical findings.

How Is the Trial Designed?

Group I: Triple Negative Breast Cancer (for tumors > 5 cm) Active Control 5 Interventions

Paclitaxel IV plus carboplatin IV (+/- pembrolizumab IV) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (+/- pembrolizumab IV) (4 cycles total)

Group II: HER2-Positive Breast Cancer Active Control 6 Interventions

Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (or PHESGO) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)

Group III: Triple Negative Breast Cancer (for tumors < 5 cm) Active Control 3 Interventions

Paclitaxel IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)

Group IV: Hormone Receptor Positive Breast Cancer Active Control 3 Interventions

Paclitaxel IV plus Carboplatin IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Baylor Breast Care Center

Lead Sponsor

Trials

16

Recruited

750+

Published Research Related to This Trial

In a trial involving patients with advanced breast cancer who had prior chemotherapy, carboplatin showed no objective responses, indicating limited efficacy in this group.

In contrast, preliminary results from an ongoing trial with patients who had no prior chemotherapy exposure showed a 32% overall response rate, suggesting that carboplatin may be more effective in treatment-naive patients, with mild toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin in advanced breast cancer: preliminary results. Martin, M., Diaz-Rubio, E., Casado, A., et al.[2013]

In a phase II trial involving 61 patients with stage II-III breast cancer, a weekly regimen of neoadjuvant chemotherapy (paclitaxel plus carboplatin) was assessed for its effectiveness, revealing that certain gene expressions could predict tumor response to treatment.

The study identified 231 differentially expressed genes, particularly those in the peroxisome proliferator-activated receptor (PPAR) pathway, which may serve as important predictors for chemotherapy response, highlighting the potential for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PPAR signaling pathway may be an important predictor of breast cancer response to neoadjuvant chemotherapy. Chen, YZ., Xue, JY., Chen, CM., et al.[2022]

In a study evaluating the effectiveness of various chemotherapy drugs on breast cancer cell lines, taxol was found to be the most potent, with an IC50 value of 0.02 microM, aligning with its strong clinical performance in treating metastatic breast cancer.

Pirarubicin also showed significant activity, being 10 times more effective than doxorubicin, suggesting it could be a valuable option in breast cancer treatment, warranting further investigation into drug combinations and testing on fresh human tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative chemosensitivity profiles in three human breast cancer cell lines with the ATP-cell viability assay. Koechli, OR., Sevin, BU., Perras, JP., et al.[2018]

In a phase II study involving 56 patients with small cell lung carcinoma, carboplatin demonstrated significant efficacy, with a 41% overall response rate and 9% achieving complete remission, particularly in previously untreated patients where the response rate was 60%.

Carboplatin showed a favorable safety profile, with no nephrotoxicity and manageable side effects; while some patients experienced myelosuppression, severe complications were rare, suggesting it may be a better-tolerated alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer. Smith, IE., Harland, SJ., Robinson, BA., et al.[2013]

Hormonal therapy is the preferred initial treatment for Stage IV breast cancer due to its lower toxicity, but response rates decline with each progression, making chemotherapy a necessary option for hormone-resistant cases.

Doxorubicin and paclitaxel are effective chemotherapy agents, with doxorubicin showing high response rates but potential cardiomyopathy at high cumulative doses, while increasing dose intensity can help overcome drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy of breast cancer. Norton, L.[2007]

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]

A 49-year-old woman with relapsing ovarian cancer experienced hypersensitivity reactions to both carboplatin and cisplatin, highlighting the potential for severe allergic responses to these chemotherapy agents.

Such hypersensitivity reactions, although rare, can limit treatment options for patients who could benefit from cisplatin-based therapies, which are known to significantly improve survival rates in certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity and cross-reactivity to cisplatin and analogues. Shlebak, AA., Clark, PI., Green, JA.[2018]

The combination of docetaxel and doxorubicin (TAC) has shown significantly higher response rates in advanced breast cancer treatment compared to traditional regimens, with a response rate of 54% versus 42% for the 5-fluorouracil/doxorubicin/cyclophosphamide regimen, based on a study involving 484 patients.

While TAC treatment was associated with a higher incidence of febrile neutropenia, it did not increase the risk of serious infections or cardiotoxicity, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the treatment of breast cancer: an update on recent studies. Nabholtz, JM., Reese, DM., Lindsay, MA., et al.[2019]

The combination of doxorubicin (Dox) and paclitaxel has been established as a superior treatment for metastatic breast cancer, showing better response rates and longer time to disease progression compared to either drug alone, based on a phase III study.

New agents like Herceptin (trastuzumab) and DPPE are being investigated to enhance the efficacy of Dox and paclitaxel, with early results indicating they may improve response rates and prolong disease progression time when used in combination with these chemotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in chemotherapy of advanced breast cancer. Lebwohl, DE., Canetta, R.[2016]

In a study of patients from the BCIRG 001 trial, certain biological markers like Ki-67 and p53 protein levels were identified as independent prognostic factors for disease-free survival (DFS) and overall survival (OS) in node-positive breast cancer patients receiving adjuvant chemotherapy.

However, these markers were not predictive of the benefit from docetaxel-containing chemotherapy, indicating that while they can help assess prognosis, they do not determine how well a patient will respond to this specific treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCIRG 001 molecular analysis: prognostic factors in node-positive breast cancer patients receiving adjuvant chemotherapy. Dumontet, C., Krajewska, M., Treilleux, I., et al.[2018]

In a dose-finding study, the combination of docetaxel and cisplatin showed a promising response rate of 60% in patients with metastatic breast cancer, indicating its potential as an effective first-line treatment option.

Carboplatin, due to its lower toxicity, may also be a viable alternative in combination with taxanes, while vinorelbine combined with docetaxel achieved a response rate of 59% in patients previously treated with anthracyclines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonanthracycline containing docetaxel-based combinations in metastatic breast cancer. Crown, J.[2019]

In a study of 170 primary breast carcinoma samples, the highest sensitivity rates to chemotherapy drugs were observed for 5-fluorouracil (57.1%) and mitomycin (49.4%), indicating these drugs may be more effective options for treating breast cancer.

Cyclosporin A was found to enhance the sensitivity of adriamycin-resistant breast carcinoma cells to adriamycin, suggesting a potential strategy to overcome drug resistance in certain breast cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemosensitivity test for 170 human breast carcinoma samples]. He, Z., Yuan, J., Chen, Z., et al.[2015]

In a study of 735 women treated with carboplatin for gynecological cancers, 10.2% experienced hypersensitivity reactions, with the incidence increasing significantly over the years from 0.88% in 2006 to 5.42% in 2013.

Risk factors for these reactions included advanced disease stage, specific cancer histologies, presence of malignant ascites, and a history of other drug allergies, suggesting that careful monitoring and potential preventive measures, like adjusting infusion rates and using desensitization protocols, could help manage these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies. Tai, YH., Tai, YJ., Hsu, HC., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11688104/

First-line carboplatin-based chemotherapy may be ... However, the results showed that carboplatin-based regimens had good efficacy and safety in HER2-low advanced breast cancer. Secondly, as of the ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P2-01-26/753736/Abstract-P2-01-26-Carboplatin-added-to-neoadjuvant

Abstract P2-01-26: Carboplatin added to neoadjuvant ... Background: Carboplatin (Cb) improves treatment efficacy among patients with triple negative breast cancer (TNBC). However, not all patients ...

3. breastcancer.org breastcancer.org/research-news/adding-carboplatin-to-chemotherapy-before-surgery-improves-early-stage-triple-negative-breast-cancer-outcomes

Adding Carboplatin to Chemotherapy Before Surgery ... Adding Carboplatin to Chemotherapy Before Surgery Improves Early-Stage Triple-Negative Breast Cancer Outcomes. Adding carboplatin (brand name: ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753422000187

Long-term efficacy and safety of addition of carboplatin with ... At 4.5 years, adding carboplatin to neoadjuvant paclitaxel followed by AC improved event-free survival in stage II-III TNBC.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12057025/

The impact of carboplatin on pathologic complete response ... Our research demonstrates that the addition of carboplatin increases pCR rates in both HER2-zero and HER2-low patient cohorts. We suggest that ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8669119/

Safety and efficacy of veliparib plus carboplatin/paclitaxel in ... Purpose: To evaluate efficacy and safety of veliparib combined with carboplatin/paclitaxel in patients with advanced human epidermal growth factor receptor 2 ( ...

7. lbbc.org lbbc.org/about-breast-cancer/treatments/chemotherapy/types/carboplatin

Carboplatin: Chemotherapy for breast cancer Carboplatin may be used to treat metastatic breast cancer. It can also be used with the chemotherapy medicines docetaxel (Taxotere) or ...