Carboplatin + Cabazitaxel for Prostate Cancer

Recruiting at 173 trial locations

Overseen by Paul Corn

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: SWOG Cancer Research Network

Disqualifiers: Prior cabazitaxel, carboplatin, brain metastases, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of adding carboplatin to the standard of care chemotherapy drug cabazitaxel versus cabazitaxel alone in treating prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels (castrate-resistant) and that has spread from where it first started (primary site) to other places in the body (metastatic). Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Chemotherapy drugs, such as cabazitaxel, 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. Prednisone is often given together with chemotherapy drugs. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs and to help the chemotherapy work. Giving carboplatin with the standard of care chemotherapy drug cabazitaxel may be better at treating metastatic castrate-resistant prostate cancer.

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

The trial requires that you stop certain treatments like chemotherapies, bone targeting therapies, immunotherapies, and clinical trial agents at least 21 days before joining. However, it doesn't specify about other medications, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of carboplatin and cabazitaxel for prostate cancer?

Research shows that cabazitaxel, when used with prednisone, can improve survival in men with advanced prostate cancer that has not responded to hormone therapy. Adding carboplatin to cabazitaxel may benefit certain types of prostate cancer, although more studies are needed to confirm this. ^{1 2 3 4 5}

Is the combination of Carboplatin and Cabazitaxel safe for humans?

Cabazitaxel, also known as Jevtana, is generally safe for humans but can cause side effects like low blood cell counts (anemia, leukopenia, neutropenia, thrombocytopenia) and diarrhea. It has been approved for use in prostate cancer treatment, indicating it has passed safety evaluations for this condition. ^{2 3 5 6 7}

How is the drug combination of carboplatin and cabazitaxel unique for prostate cancer treatment?

The combination of carboplatin and cabazitaxel is unique for treating metastatic castration-resistant prostate cancer because it targets distinct biological subsets of the disease that may benefit from the addition of platinum, potentially improving outcomes compared to other treatments. ^{1 2 3 4 5}

Research Team

Paul Corn

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with castrate-resistant prostate cancer that has spread, who have previously been treated with docetaxel. They must have a confirmed diagnosis and available tumor biopsy material. Participants need to consent to the study and can provide tissue samples collected within the last year.

Inclusion Criteria

I have a confirmed diagnosis of prostate cancer.

My prostate cancer is resistant to hormone therapy and has spread, shown by scans.

I have had treatment for my cancer that included docetaxel.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cabazitaxel with or without carboplatin and prednisone for up to 10 cycles, each cycle lasting 21 days

30 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 12 weeks for 1 year, then every 26 weeks

Treatment Details

Interventions

• Cabazitaxel (Anti-tumor antibiotic)
• Carboplatin (Alkylating agents)

Trial Overview The trial is testing if adding Carboplatin to standard Cabazitaxel chemotherapy improves outcomes in metastatic castrate-resistant prostate cancer. Prednisone will also be used to reduce side effects and help chemotherapy work better.

Participant Groups

Group I: Arm 2 (cabazitaxel, carboplatin, prednisone) Experimental Treatment 9 Interventions

Patients receive cabazitaxel and carboplatin IV over 60 minutes on day 1 of each cycle and prednisone PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, CT, PET, or MRI throughout the trial and chest x-ray before randomization.

Group II: Arm 1 (cabazitaxel, prednisone) Active Control 8 Interventions

Patients receive cabazitaxel IV over 60 minutes on day 1 of each cycle and prednisone PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, CT, PET, or MRI throughout the trial and chest x-ray before randomization.

Cabazitaxel is already approved in Canada, Japan for the following indications:

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Dr. Charles D. Blanke

SWOG Cancer Research Network

Chief Executive Officer since 2012

MD from Oregon Health & Science University

Dr. Dawn Hershman

SWOG Cancer Research Network

Chief Medical Officer since 2020

MD from Columbia University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Adding carboplatin to cabazitaxel significantly improved progression-free survival in men with metastatic castration-resistant prostate cancer, increasing the median survival from 4.5 months to 7.3 months in a phase 2 trial with 160 participants.

While the combination treatment had more adverse events compared to cabazitaxel alone, it was still considered safe and well tolerated, with no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: a randomised, open-label, phase 1-2 trial. Corn, PG., Heath, EI., Zurita, A., et al.[2021]

Cabazitaxel is an effective second-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC), showing a median survival of 15.1 months compared to 12.7 months with mitoxantrone in a randomized trial.

While cabazitaxel has demonstrated efficacy, it is associated with significant adverse effects, including myelosuppression and febrile neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. Nightingale, G., Ryu, J.[2023]

Cabazitaxel, when combined with prednisone, significantly improves overall survival in patients with hormone-refractory metastatic prostate cancer who have previously been treated with docetaxel, as shown in the pivotal TROPIC trial.

The treatment also enhances progression-free survival and response rates for tumor and PSA levels, while maintaining an acceptable safety profile, with common side effects including hematological issues and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. Keating, GM.[2021]

Cabazitaxel, a new chemotherapy drug, has been shown to improve overall survival by 2.4 months in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment, compared to the older drug mitoxantrone.

While cabazitaxel is effective, it carries a risk of significant hematologic toxicity, including febrile neutropenia, necessitating the use of hematopoietic growth factors in cases of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer]. Lheureux, S., Joly, F.[2018]

Cabazitaxel (Jevtana®) is an effective treatment for hormone-refractory metastatic prostate cancer, showing a 2.4-month increase in median overall survival and a 30% reduction in the risk of death compared to mitoxantrone, based on the main study for its EU approval.

The recommended dosage is 25 mg/m2 administered every 3 weeks via intravenous infusion, alongside daily oral prednisone, with common side effects including anemia and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of cabazitaxel (Jevtana®) for the treatment of hormone-refractory metastatic prostate cancer: summary of the scientific assessment of the committee for medicinal products for human use. Pean, E., Demolis, P., Moreau, A., et al.[2021]

Cabazitaxel is a potentially effective treatment for castration-resistant prostate cancer (CRPC) in patients aged 80 years and older, showing similar efficacy in overall survival and PSA response rates compared to younger patients.

The safety profile of cabazitaxel is comparable across age groups, with high rates of adverse drug reactions (ADRs) in both patients aged <80 (77.2%) and ≥80 years (79.6%), primarily involving hematologic toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. Matsubara, N., Suzuki, K., Kazama, H., et al.[2021]

Cabazitaxel, marketed as Jevtana, is an FDA-approved treatment for hormone-refractory prostate cancer that is resistant to docetaxel, showing efficacy in patients who have failed previous treatments.

As a microtubule depolymerization inhibitor, cabazitaxel can penetrate the blood-brain barrier and is administered in combination with prednisone, providing a new option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a novel drug for hormone-refractory prostate cancer. Malhotra, M., Dhingra, R., Sharma, T., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: a randomised, open-label, phase 1-2 trial. [2021]

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

Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. [2021]

4. France pubmed.ncbi.nlm.nih.gov

[Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer]. [2018]

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

The European Medicines Agency review of cabazitaxel (Jevtana®) for the treatment of hormone-refractory metastatic prostate cancer: summary of the scientific assessment of the committee for medicinal products for human use. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a novel drug for hormone-refractory prostate cancer. [2019]