Marker-Directed Monitoring for Breast Cancer

Recruiting at 678 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: SWOG Cancer Research Network

Must be taking: Endocrine therapy

Disqualifiers: Cirrhosis, Untreated B12 deficiency, Thalassemia, others

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

Compensation: Varies

Number of Visits: 4

Duration: 312 weeks

739 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for monitoring breast cancer that has spread in individuals with hormone receptor-positive, HER2-negative types. Researchers aim to determine if blood tests can effectively guide the timing of scans compared to the standard practice of regular scans. Participants are divided into two groups: one follows the usual care disease monitoring, while the other uses serum tumor marker-directed disease monitoring, which relies on blood tests to decide when scans are necessary. This trial may suit those with metastatic breast cancer who are undergoing their first round of treatment and have specific tumor marker levels in their blood.

As an unphased trial, this study provides a unique opportunity to contribute to innovative monitoring methods that could enhance future breast cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be receiving or plan to receive first-line systemic treatment for metastatic breast cancer, which may include endocrine therapy, targeted therapy, or chemotherapy.

What prior data suggests that serum tumor marker directed disease monitoring is safe for monitoring breast cancer?

Research has shown that monitoring breast cancer using serum tumor markers, proteins found in the blood, is generally safe. Studies use this method to determine if the cancer is spreading or recurring, reducing the need for frequent scans. Patients have tolerated this approach well, with no reports of serious side effects directly linked to it. This method aids in deciding when additional imaging tests are necessary, potentially making it less invasive than standard care. However, discussing personal risks and benefits with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Marker-Directed Monitoring for Breast Cancer trial because it explores a new way of tracking disease progression using serum tumor markers (STMs) instead of just traditional imaging. This method involves evaluating specific blood markers, like CEA and either CA 15-3 or CA 27.29, every 4-8 weeks, potentially offering a less invasive, quicker, and more personalized approach to monitoring the disease. By detecting changes in these markers, doctors may identify disease progression earlier and tailor treatments more effectively. This could lead to more timely interventions and potentially improve outcomes for patients.

What evidence suggests that serum tumor marker directed disease monitoring is effective for monitoring hormone receptor positive Her2 negative breast cancer?

This trial will compare two monitoring approaches for breast cancer. One group will receive usual care, involving imaging studies at least every 12 weeks. The other group will undergo serum tumor marker-directed disease monitoring, using blood tests to track specific proteins like CEA and CA 15-3. Studies have shown that these blood tests can be as effective as the usual methods. An increase in these markers may indicate cancer progression, prompting further imaging checks. Early findings suggest that using these markers could reliably monitor the disease without frequent scans. ^{3 4 6 7 8}

Who Is on the Research Team?

Melissa Accordino

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with hormone receptor positive, HER2 negative metastatic breast cancer who are starting or receiving first-line systemic treatment. They must not be pregnant, have had other cancers (except certain skin/cervical cancers) in the last five years, or conditions like cirrhosis that affect tumor marker levels. Participants need decision-making capacity and can't be in another first-line treatment trial.

Inclusion Criteria

I am not in, nor planning to join, another first-line treatment trial for my metastatic breast cancer.

Patients must not be pregnant

I have not had systemic therapy for my metastatic breast cancer, except my current treatment.

Exclusion Criteria

I have cancer that has spread to the lining of my brain.

I have cirrhosis, untreated B12 deficiency, thalassemia, or sickle cell anemia.

Patients must not have known progression since registration to step 1

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo either usual care disease monitoring or serum tumor marker directed disease monitoring (STMDDM) for up to 312 weeks

312 weeks

Every 4-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

102 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Serum Tumor Marker directed disease monitoring
• Usual care disease monitoring

Trial Overview The study compares usual care disease monitoring to serum tumor marker directed monitoring to see if using blood markers to decide when to do scans is as effective for patients with advanced breast cancer. It includes quality-of-life assessments and anxiety questionnaires.

How Is the Trial Designed?

Group I: Arm II (serum tumor directed disease monitoring) Experimental Treatment 3 Interventions

Patients undergo disease specific serum tumor marker evaluation (CEA and either CA 15-3 or CA 27.29, whichever were tested at Step 1 Registration and Step 2 Registration) every 4-8 weeks (starting from randomization) without imaging until an elevation of at least one disease specific STM. In the event of an elevated STM, the patient will have imaging within 4 weeks to evaluate for disease progression. Patients continue with STMDDM for up to 312 weeks in the absence of disease progression.

Group II: Arm I (usual care) Active Control 3 Interventions

Patients will have imaging studies (modality and frequency per treating physician, however at a minimum frequency of every 12 weeks) alone or in conjunction with STMs (frequency determined by treating physician). Patients will continue with usual care disease monitoring for up to 312 weeks in the absence of disease progression.

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Current serum tumor markers have limited sensitivity and specificity, making them unsuitable for screening asymptomatic individuals for cancer.

While tumor markers are not ideal for initial diagnosis, they are valuable for monitoring treatment effectiveness and detecting cancer recurrence, providing important prognostic information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of tumour markers in clinical practice]. Keuren, JF., Thomas, CM., Bonfrèr, JM., et al.[2015]

The study found a 125% increase in tumour marker requests over five years, indicating a growing reliance on these tests in cancer management, but many requests were inappropriate, such as being made for the wrong sex or before a cancer diagnosis.

Out of 34 case notes reviewed, many tumour markers were measured before necessary biopsies, leading to potentially misleading results, as some patients with normal markers still had malignancies, while others with raised markers had normal biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour markers: their use and misuse by clinicians. McGinley, PJ., Kilpatrick, ES.[2015]

Antibody-drug conjugates (ADCs) are a promising treatment for breast cancer, effectively delivering cytotoxic drugs directly to tumors while minimizing systemic toxicity, making them generally well tolerated.

Despite their benefits, ADCs can cause predictable side effects such as neutropenia and nausea, which require careful monitoring and management to prevent treatment interruptions or dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations. D'Arienzo, A., Verrazzo, A., Pagliuca, M., et al.[2023]

Antibody-drug conjugates (ADCs) are a promising cancer treatment that combines targeted monoclonal antibodies with cytotoxic agents to deliver drugs directly to cancer cells, minimizing harm to healthy cells.

Despite their targeted approach, ADCs can still cause adverse events due to early payload release or target expression in normal cells, highlighting the need for careful monitoring and dose adjustments to optimize their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for Mitigating Antibody-Drug Conjugate Related Adverse Events for Precision Therapy. Gouda, MA., Subbiah, V.[2022]

Breast cancer is the most common non-skin cancer in women, with over 80% of patients diagnosed at early stages, but there is a critical need for effective treatments for those with metastatic disease.

Antibody drug conjugates (ADCs) are promising therapies that use monoclonal antibodies to selectively deliver cytotoxic drugs to cancer cells, showing clinical potential in treating both hematologic malignancies and solid tumors, including breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody drug conjugates for treatment of breast cancer: Novel targets and diverse approaches in ADC design. Trail, PA., Dubowchik, GM., Lowinger, TB.[2018]

A novel drug discovery method identified a compound, DBBF, that specifically inhibits the growth of triple-negative breast cancer (TNBC) cell line MDA-MB-468 with an IC50 of 2.4 μM, indicating its potential as a targeted treatment.

The study revealed changes in several signaling pathways, including the irinotecan pathway, upon treatment with DBBF, suggesting new therapeutic targets for TNBC and enhancing the understanding of its biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a novel inhibitor of triple-negative breast cancer cell growth by screening of a small-molecule library. Fujita, T., Mizukami, T., Okawara, T., et al.[2014]

In a study of 39,650 early-stage breast cancer survivors, 42% underwent tumor marker assessments, averaging 5.7 tests over two years, despite guidelines discouraging routine use.

Patients who received tumor marker tests incurred approximately 29% higher medical costs compared to those who did not, indicating a significant financial impact associated with their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor marker usage and medical care costs among older early-stage breast cancer survivors. Ramsey, SD., Henry, NL., Gralow, JR., et al.[2022]

Serum tumor markers are a cost-effective and noninvasive method for monitoring breast cancer patients, providing insights into disease presence and progression, although their effectiveness in therapy response evaluation remains debated among experts.

Recent advancements in imaging technology, like hybrid PET-CT scans, can detect early cancer lesions that may cause elevated serum tumor marker levels, suggesting that these markers can guide further diagnostic procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of traditional serum biomarkers for management of breast cancer patients. Mirabelli, P., Incoronato, M.[2021]

Serum tumor markers like CA 15-3 and CEA are not recommended for screening or diagnosing breast cancer due to their low sensitivity, but they can indicate recurrence 3-6 months earlier than traditional methods in about 40-50% of patients.

While tumor markers can monitor treatment response in 70-80% of metastatic breast cancer patients, their inconsistent results and the need for confirmation through imaging limit their routine clinical use, highlighting the need for improved assays and evaluation of newer markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Considerations in rational use of tumor markers in breast carcinoma]. Crombach, G.[2015]

Serum tumor markers, particularly CA15-3, CA27.29, and c-erbB-2, can be useful for early detection of breast cancer recurrence, but their effectiveness in diagnosing cancer or determining disease progression is limited.

Currently, c-erbB-2 is the only marker with clinical evidence supporting its use for evaluating prognosis and predicting therapy response, yet no serum tumor marker is considered cost-effective or reliable for decision-making in breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum tumor markers in patients with breast cancer. Lumachi, F., Basso, SM.[2015]

Current clinical practice primarily uses CA 15.3, CEA, and cytokeratins as serum markers for breast cancer, but these markers are not sensitive enough for early detection of primary breast cancer.

Tumor markers are effective for diagnosing recurrent disease and monitoring treatment response, offering advantages over traditional imaging methods, though further randomized studies are needed to confirm any survival benefits from early interventions based on marker elevation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumour markers in breast cancer. Seregni, E., Coli, A., Mazzucca, N.[2018]

Breast cancer is a complex disease with various subtypes, making it challenging to predict patient outcomes, highlighting the need for effective biomarkers to guide treatment decisions.

Recent studies suggest that circulating proteins obtained through liquid biopsy could serve as valuable, non-invasive biomarkers for early diagnosis, treatment adjustment, and monitoring disease progression in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating proteins as predictive and prognostic biomarkers in breast cancer. Veyssière, H., Bidet, Y., Penault-Llorca, F., et al.[2023]

Antibody-drug conjugates (ADCs) are a new class of targeted cancer treatments that combine the tumor-targeting ability of antibodies with the powerful effects of cytotoxic drugs, significantly improving treatment options for certain breast cancer subtypes.

While ADCs generally have favorable safety profiles, they can cause specific adverse reactions such as thrombocytopenia and hepatotoxicity, necessitating careful monitoring and management by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chinese expert consensus of antibody-drug conjugate toxicity management for breast cancer]. [2022]

Using serum markers to assess therapeutic response in patients with advanced breast cancer could provide equivalent quality assessments compared to traditional methods, but at a lower cost.

The potential cost savings from using serum markers are significant enough to warrant the initiation of a randomized controlled trial to further investigate their efficacy and practicality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential for cost economies in guiding therapy in patients with metastatic breast cancer. Robertson, JF., Whynes, DK., Dixon, A., et al.[2019]

Establishing a pretreatment baseline and conducting regular serial testing of serum tumor markers can significantly enhance the effectiveness of patient monitoring in cancer care.

Clinical decisions regarding therapy changes should not rely solely on tumor marker measurements; confirmation with serial samples and consideration of other clinical data is essential for accurate interpretation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum tumor markers for patient monitoring: a case-oriented approach illustrated with carcinoembryonic antigen. Fritsche, HA.[2019]

Citations

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Randomized Non-Inferiority Trial Comparing Overall ... Randomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored with Serum Tumor Marker Directed Disease Monitoring STMDDM versus Usual Care ...

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S1703 Schema The goal of this study is to see if a different monitoring approach, called serum tumor marker directed disease monitoring, using the trend of patient tumor ...

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Exploring Biomarkers in Breast Cancer: Hallmarks of ... It is frequently utilized as a tumor marker for detecting and monitoring breast cancer [36]. However, it is noteworthy that CA 15-3 levels can also rise in ...

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S1703 Serum Tumor Marker Directed Disease Monitoring ... This randomized research trial studies how well serum tumor marker directed disease monitoring works in monitoring patients with hormone ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804998002974

The objective measurement of remission and progression ... The index uses two serum tumour markers—carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) along with erythrocyte sedimentation rate (ESR).

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S1703 Serum Tumor Marker Directed Disease Monitoring ... This randomized research trial studies how well serum tumor marker directed disease monitoring works in monitoring patients with hormone receptor positive ...

7. sjchs.org sjchs.org/clinical-trials/trial/s1703--randomized-non-inferiority-trial-comparing-overall-survival-of-patients-monitored-with-serum-tumor-marker-directed-disease-monitoring-(stmddm)-versus-usual-care-in-patients-with-metastatic-hormone-receptor-positive-breast-cancer

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Comparing Overall Survival using Markers to Direct Cancer ... This clinical trial studies how well serum tumor marker directed disease monitoring works in monitoring patients with hormone receptor positive HER-2 ...