Radium Therapy + Chemotherapy for Metastatic Breast Cancer

Not currently recruiting at 30 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Bisphosphonates, Denosumab

Must not be taking: Radionuclides, Immunosuppressants

Disqualifiers: Peripheral neuropathy, Active infection, 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

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining radium-223 dichloride, a radioactive drug, with paclitaxel, a chemotherapy drug, for treating advanced breast cancer that has spread to the bones. Radium-223 targets bone metastases, helping to kill tumor cells and reduce pain. The trial compares this combination treatment to paclitaxel alone to determine if it offers better results. Ideal participants are those diagnosed with metastatic breast cancer, have multiple bone metastases, and have not received paclitaxel in the last few years. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in cancer care.

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.

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

Research has shown that combining radium-223 and paclitaxel is generally safe for cancer patients with bone metastases. Studies found no major side effects when these treatments were used together, meaning most patients did not experience serious additional problems. The safety results for breast cancer patients mirrored those for all patients, indicating consistent safety across different cancer types. This is encouraging for those considering joining a trial with these treatments. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for metastatic breast cancer?

Researchers are excited about these treatments for metastatic breast cancer because they explore the potential of combining radium therapy with traditional chemotherapy. Unlike standard care options, which often rely solely on chemotherapy agents like paclitaxel, this approach introduces radium Ra 223 dichloride. This radioactive compound specifically targets bone metastases by delivering radiation directly to cancer cells in the bone, potentially enhancing the overall effectiveness. The combination of radium Ra 223 with paclitaxel might offer a dual approach: attacking cancer cells systemically with chemotherapy and targeting bone metastases with radium, which could lead to improved outcomes for patients with metastatic breast cancer.

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

In this trial, participants in one arm will receive a combination of radium-223 dichloride and paclitaxel. Studies have shown that radium-223 dichloride targets cancer that has spread to the bones by releasing tiny radioactive particles that directly attack and kill cancer cells there. Paclitaxel, a chemotherapy drug, stops cancer cells from growing and dividing. Research indicates that this combination may delay disease progression compared to using paclitaxel alone, which is the treatment in another arm of this trial. Patients with breast cancer that has spread to the bones have reported tolerating this combination well. Early studies suggest it could be a promising option for treating advanced breast cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Jyoti Malhotra, MD

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6451720/

Radium-223 in combination with paclitaxel in cancer ...

In conclusion, radium-223 was well tolerated when combined with paclitaxel in cancer patients with bone metastases, with no clinically relevant additive ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04090398

NCT04090398 | Testing the Addition of Radium Therapy ...

Giving radium-223 dichloride and paclitaxel may work better in treating patients with metastatic breast cancer compared to paclitaxel alone. PRIMARY OBJECTIVE: ...

3.

clinicaltrials.med.nyu.edu

clinicaltrials.med.nyu.edu/cancer/clinicaltrial/1812/phase-ii-trial-radium-223/

Perlmutter Cancer Center - Clinical Trials - NYU

We want to know if the combination of Radium-223 dichloride and paclitaxel can prolong progression-free survival (PFS) when compared to paclitaxel alone.

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30547207/

Radium-223 in combination with paclitaxel in cancer ...

Breast cancer subgroup safety results were similar to the overall safety population. Conclusion: Radium-223 was tolerated when combined with weekly paclitaxel, ...

5.

frontiersin.org

frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.896301/full

Radium-223 as an Additional Therapeutic Strategy in ...

While our patient rapidly progressed during the previous chemotherapy regimen, the progression-free survival on radium-223 reached 6 months with an excellent ...

6.

aacrjournals.org

aacrjournals.org/cancerres/article/78/4_Supplement/P1-16-03/632174/Abstract-P1-16-03-An-open-label-multicenter-phase

Abstract P1-16-03: An open-label, multicenter phase 1b trial of ...

An open-label, multicenter phase 1b trial of radium-223 + paclitaxel in cancer patients with bone metastases: Safety results from the breast ...