Radium Therapy + Chemotherapy for Metastatic Breast Cancer

Recruiting at 30 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well radium-223 dichloride and paclitaxel work in treating patients with advanced breast cancer that has spread to the bones. Radium-223 dichloride is a radioactive drug that behaves in a similar way to calcium and collects in cancer that has spread to the bones (bone metastases). The radioactive particles in radium-223 dichloride act on bone metastases, killing the tumor cells and reducing the pain that they can cause. Drugs used in chemotherapy, such as paclitaxel, 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. Giving radium-223 dichloride and paclitaxel may work better in treating patients with metastatic breast cancer compared to paclitaxel alone.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had chemotherapy or immunotherapy within 4 weeks before starting the trial, and there is a required washout period for investigational agents. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Radium Therapy + Chemotherapy for Metastatic Breast Cancer?

Research shows that taxane-based chemotherapy, which includes drugs like paclitaxel, is effective in treating metastatic prostate cancer, suggesting potential benefits for other cancers. Additionally, radium-223 combined with paclitaxel has been explored for safety in patients with bone metastases, indicating its potential use in similar conditions. ^{1 2 3 4 5}

Is the combination of Radium Therapy and Chemotherapy safe for humans?

Nab-paclitaxel (Abraxane) is generally considered safe with less toxicity compared to traditional paclitaxel (Taxol), and it has been approved for treating several cancers, including breast cancer. However, it can cause side effects like neutropenia (low white blood cell count), which is a major concern. The combination of paclitaxel with other drugs like carboplatin has shown significant activity in various cancers, but the safety of combining it with Radium-223 is not specifically addressed in the available research. ^{6 7 8 9 10}

What makes the combination of radium therapy and paclitaxel unique for treating metastatic breast cancer?

This treatment is unique because it combines radium-223, which targets and kills cancer cells in the bones, with paclitaxel, a chemotherapy drug that stops cancer cells from growing. This combination may offer a new approach for patients with bone metastases, although the safety of using both together is still being studied. ^{2 11 12 13 14}

Research Team

Jyoti Malhotra, MD

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

This trial is for adults with advanced breast cancer that has spread to the bones. Participants must have good performance status, confirmed diagnosis, specific blood and organ function levels, and at least one untreated bone lesion. They should not have had certain treatments recently and must agree to contraception if of childbearing potential.

Inclusion Criteria

My kidney function, measured by creatinine or GFR, is within the required range.

My breast cancer diagnosis was confirmed through testing.

I can be treated with paclitaxel for my breast cancer and have tried other treatments if my cancer is hormone-receptor positive.

Exclusion Criteria

I haven't taken strong immune-suppressing drugs in the last week, except for low-dose or topical steroids, or if I have Crohn's or ulcerative colitis.

I have had radiation treatment on half of my body.

I do not have an infection that needs treatment with medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive paclitaxel and radium Ra 223 dichloride, with cycles repeating every 28 days for up to 6 cycles

24 weeks

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Every 3 months

Treatment Details

Interventions

• Paclitaxel
• Radium-223 Dichloride

Trial Overview The study is testing whether adding Radium-223 Dichloride (a radioactive drug targeting bone metastases) to Paclitaxel (a chemotherapy drug) provides better outcomes than Paclitaxel alone in treating patients with breast cancer that has spread to the bones.

Participant Groups

Group I: Arm I (paclitaxel, radium Ra 223 dichloride) Experimental Treatment 8 Interventions

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and radium Ra 223 dichloride IV over 1 minute on day 1 of each cycle. Treatment with radium Ra 223 dichloride repeats every 28 days for 6 cycles and treatment with paclitaxel repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, bone scan and/or MRI, as well as collection of blood samples throughout trial. Patients may optionally undergo SPECT on trial.

Group II: Arm II (paclitaxel) Active Control 7 Interventions

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, bone scan, and/or MRI, as well as collection of blood samples throughout trial. Patients may optionally undergo SPECT on trial.

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The combination of docetaxel and zoledronic acid in treating 14 patients with metastatic hormone-refractory prostate cancer was found to be safe, with no reported drug-related toxicity and minimal need for blood transfusions.

More than half of the patients experienced a significant reduction in prostate-specific antigen (PSA) levels by over 50% after 2 months, indicating potential efficacy, although further randomized trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer. Vordos, D., Paule, B., Vacherot, F., et al.[2018]

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Metastatic prostate cancer : Update: position paper for the use of chemotherapy]. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Radium-223 in combination with paclitaxel in cancer patients with bone metastases: safety results from an open-label, multicenter phase Ib study. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Taxane-induced Attenuation of the CXCR2/BCL-2 Axis Sensitizes Prostate Cancer to Platinum-based Treatment. [2022]

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

First-line treatment in senior adults with metastatic castration-resistant prostate cancer: A prospective international registry. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

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

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]

8. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

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

Chemotherapy following radium-223 dichloride treatment in ALSYMPCA. [2022]

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

Phase II study of Radium-223 dichloride combined with hormonal therapy for hormone receptor-positive, bone-dominant metastatic breast cancer. [2021]

13. Italy pubmed.ncbi.nlm.nih.gov

Bone pain palliation outcomes and possibility of Radium-223 re-treatment in mCRPC. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Circulating tumor cells and γH2AX as biomarkers for responsiveness to radium-223 in advanced prostate cancer patients. [2022]