Chemotherapy + Endocrine Therapy for Breast Cancer

(INSIGHT Trial)

Recruiting at 2 trial locations

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sonya Reid

Disqualifiers: Prior chemotherapy, Recent cancer, Pregnancy, 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: Unknown

Duration: 6 months

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the chemotherapy drug capecitabine, combined with hormone therapy (endocrine therapy), can improve survival for individuals with a specific type of advanced breast cancer. Researchers aim to evaluate the effectiveness of this treatment for patients whose breast cancer is hormone receptor-positive but not Luminal A, and has spread beyond the breast. The trial includes two groups: one receiving capecitabine and the other receiving a doctor-selected hormone therapy. Suitable candidates for this trial are those with metastatic breast cancer who have previously undergone treatment with certain hormone therapies and a CDK4/6 inhibitor. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that prior chemotherapy in the metastatic setting is not allowed, which might imply some restrictions. 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 shows that capecitabine, an oral chemotherapy drug, is generally well-tolerated by patients with advanced breast cancer. Studies have found that it can effectively control tumors even in patients who have undergone many previous treatments. However, while capecitabine works well, it can cause some serious side effects.

Common side effects include skin reactions on the hands and feet, diarrhea, and tiredness. Despite these side effects, capecitabine has been used safely in other approved treatments, indicating a good safety record.

Prospective trial participants should discuss the possible side effects and benefits with healthcare providers. This discussion will help in understanding what to expect and how to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new hope for non-luminal A subtype breast cancer. Capecitabine, a chemotherapy drug, is unique because it is taken orally, unlike many standard chemotherapy drugs that require intravenous administration. This could make treatment more convenient and comfortable for patients. Meanwhile, the physician's choice of endocrine-based therapy allows for personalized treatment, tailoring the approach to the specific needs of the patient. These treatments aim to improve outcomes and quality of life for those with this challenging type of breast cancer.

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

Research shows that capecitabine, which participants in this trial may receive, effectively treats metastatic breast cancer. Studies indicate that chemotherapy with capecitabine improves both the response rate and the duration patients live without their cancer worsening in advanced breast cancer. However, it does not always extend overall survival. Capecitabine often serves as the first treatment for advanced breast cancer, and while real-world data is limited, clinical trials support its use. Additionally, capecitabine has improved survival in people with HER2-negative breast cancer when used as an additional treatment after the main one. ^{1 2 3 6 7}

Who Is on the Research Team?

Sonya Reid

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with HR+ metastatic breast cancer who have progressed after specific hormone therapies. They must be in good physical condition, have measurable disease, and their major organs need to function well. Pregnant women, those with recent radiation therapy or certain previous cancers are excluded.

Inclusion Criteria

My cancer can be measured or observed.

My breast cancer is advanced, ER/PR positive, and HER2 negative.

You have at least one lesion that can be measured according to specific guidelines. If you had radiation treatment to a lesion, it can only be counted as a measurable lesion if it has shown clear signs of getting worse after the treatment.

Exclusion Criteria

I haven't had cancer other than breast cancer in the last 5 years, except for skin cancer, cervical pre-cancer, or low-risk cancers that were cured over 2 years ago.

I have brain metastases but have been stable for over 4 weeks after radiation and am not on steroids.

I have received chemotherapy for cancer that has spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either capecitabine or an endocrine-based therapy regimen

6 months

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Periodic visits for assessment

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Endocrine-therapy

Trial Overview The study tests the effectiveness of capecitabine chemotherapy on survival rates compared to standard endocrine therapy in patients whose tumors are non-Luminal A as determined by MammoPrint® and BluePrint® assays.

How Is the Trial Designed?

Group I: Capecitabine_Non-Luminal A subtypes Experimental Treatment 2 Interventions

Group II: Physician's Choice of Endocrine-based Therapy_Non-Luminal A subtypes Active Control 2 Interventions

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Sonya Reid

Lead Sponsor

Trials

1

Recruited

60+

Agendia

Industry Sponsor

Trials

18

Recruited

44,100+

Susan G. Komen Breast Cancer Foundation

Collaborator

Trials

68

Recruited

220,000+

Published Research Related to This Trial

In a study of 423 postmenopausal women with advanced breast cancer, those who progressed on fulvestrant still showed some sensitivity to subsequent endocrine therapies, with 54 patients experiencing clinical benefit from further treatment.

Fulvestrant can be an effective option in the treatment sequence for advanced breast cancer, potentially allowing patients to avoid cytotoxic chemotherapy longer by extending the use of endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. Vergote, I., Robertson, JF., Kleeberg, U., et al.[2019]

In patients with hormone receptor-positive advanced breast cancer, fulvestrant is as effective as third-generation aromatase inhibitors like anastrozole and letrozole, providing a valuable treatment option after resistance to other endocrine therapies develops.

Fulvestrant is well tolerated compared to cytotoxic chemotherapy, making it a preferable choice for patients, as it helps delay the need for more aggressive treatments that can significantly impact quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex')--a new hormonal treatment for advanced breast cancer. Lynn, J.[2018]

Xeloda (capecitabine) is an oral medication designed to convert into 5-fluorouracil (5-FU) specifically within tumors, potentially increasing anti-tumor activity while reducing systemic toxicity, as shown in various phase I and II trials.

In a phase II trial for colorectal cancer, Xeloda demonstrated a response rate of 21-24% across different regimens, with good tolerability and a longer time to disease progression for the intermittent regimen, which was selected for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Xeloda in colorectal cancer and other solid tumors. Cassidy, J.[2017]

Endocrine therapy has been a crucial treatment for postmenopausal women with estrogen receptor-positive breast cancer, significantly improving survival rates over the past 20 years.

Fulvestrant ('Faslodex') is highlighted as a novel endocrine therapy with a unique mechanism of action that may help overcome the acquired resistance that often leads to cancer relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex'): extending the reach of endocrine therapy? Johnston, SR.[2018]

For patients with estrogen receptor positive metastatic breast cancer that does not respond to first-line endocrine therapies, sequential treatment options include progestins, antiadrenal drugs, and androgens to maximize disease palliation.

Chemotherapy regimens like CMF and FAC are effective for these patients, with response rates ranging from 45% to 55%, while other combinations and drugs can provide additional options with varying levels of antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapeutic approaches to advanced breast cancer. Buzdar, AU.[2018]

Endocrine therapies for hormone receptor-positive advanced breast cancer, such as tamoxifen and aromatase inhibitors, are generally well tolerated, making them a preferred treatment option.

However, adding targeted therapies like palbociclib or everolimus to these treatments can increase the risk of adverse events, with palbociclib and chemotherapy being associated with more serious side effects like neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer. Ohno, S.[2018]

Fulvestrant is a selective estrogen receptor down-regulator (SERD) that has shown significant efficacy and a strong safety profile in treating postmenopausal women with hormone-receptor positive metastatic breast cancer.

Combining fulvestrant with targeted therapies has demonstrated increased effectiveness, suggesting it may become a new standard treatment, with ongoing clinical trials (FALCON and FEVEX) expected to provide further insights into its optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients. Poggio, F., Lambertini, M., Blondeaux, E., et al.[2018]

The combination of fulvestrant and vinorelbine showed promising efficacy in treating hormone receptor positive (HR+)/HER2-negative recurrent or metastatic breast cancer, with a median progression-free survival (PFS) of 9.86 months for 38 patients followed for an average of 25.1 months.

The treatment was found to be safe, with most adverse events being mild (grade 1/2) and no severe (grade 4/5) events reported, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined chemo-endocrine therapy as a potential new option for HR+/HER2- advanced breast cancer: a prospective study of fulvestrant plus oral vinorelbine. Wang, X., Yue, J., Kang, Y., et al.[2023]

Capecitabine (Xeloda) is an oral chemotherapy that delivers 5-FU directly to tumors, offering superior response rates and equivalent survival outcomes compared to intravenous 5-FU in first-line metastatic colorectal cancer (MCRC).

Capecitabine has a favorable safety profile, with manageable side effects like hand-foot syndrome and diarrhea, allowing for prompt dose adjustments without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. Sternberg, CN., Reichardt, P., Holland, M.[2015]

Capecitabine is a well-tolerated treatment for metastatic breast cancer, showing minimal side effects like myelosuppression and hair loss, which makes it a promising option for combination therapies with other anticancer drugs.

Ongoing phase II/III trials are investigating the use of capecitabine in early breast cancer treatment, and preliminary results indicate that it may provide significant benefits when used as part of adjuvant and neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. Fumoleau, P., Cameron, D.[2019]

In a study of 42 patients with advanced breast and colorectal cancer, capecitabine showed a partial response rate of 29.16% for breast cancer and 11.76% for colorectal cancer, indicating its potential efficacy in these pretreated patients.

Capecitabine was well tolerated with low toxicity levels, as most adverse reactions were mild, although 7.14% of patients experienced grade 3 hand-foot syndrome, and hypertriglyceridemia was noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. Stathopoulos, GP., Koutantos, J., Lazaki, H., et al.[2022]

Xeloda (capecitabine) is an effective oral treatment for metastatic breast cancer patients who have not responded to anthracycline and paclitaxel chemotherapy, showing a 20% overall response rate in a phase II trial with 163 patients and a median survival of 12.8 months.

Xeloda is well tolerated, with common side effects including hand-foot syndrome and nausea, and it has demonstrated higher response rates compared to paclitaxel and cyclophosphamide/methotrexate/5-FU in additional studies, making it a valuable option for patients with limited treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xeloda in the treatment of metastatic breast cancer. Blum, JL.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4770778/

Efficacy and safety of capecitabine-based first-line ... Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12036065/

Efficacy of adjuvant capecitabine in triple-negative breast ... Adjuvant capecitabine therapy significantly improved the prognosis of patients with TNBC who had residual disease after NAT.

3. ascopubs.org ascopubs.org/doi/10.1200/OA-24-00068

Randomized Trial of Fixed-Dose Capecitabine Compared ... Oral capecitabine administered for 14 days followed by a 7-day rest period is effective in metastatic breast cancer but results in significant ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1612645

Adjuvant Capecitabine for Breast Cancer after ... The addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative ...

5. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/view/38886/46669

Capecitabine monotherapy as first-line treatment in ... Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse.

6. esmoopen.com esmoopen.com/article/S2059-7029(25)01437-1/fulltext

Adjuvant capecitabine in patients with triple-negative ... In terms of outcomes, among patients with TNBC in CREATE-X, the 5-year DFS rate was significantly higher in patients treated with capecitabine ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)63602-1/fulltext

Multicenter phase II study of oral capecitabine (Xeloda“) in ... This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated patients with metastatic breast cancer.