Docetaxel + Radium 223 for Prostate Cancer

No longer recruiting at 3 trial locations

Overseen By Latoya Lashley, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tufts Medical Center

Must be taking: Androgen deprivation therapy

Must not be taking: Antiandrogens, Myelosuppressive agents

Disqualifiers: Peripheral neuropathy, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, docetaxel (a chemotherapy drug) and Radium 223, to determine the safest and most effective dose for treating prostate cancer that has spread and resists standard hormone therapy. Researchers focus on how these drugs work together and what side effects might occur. Men with prostate cancer that has spread to the bones and not responded to hormone treatments might be suitable for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial requires that you stop antiandrogen therapy at least 4 weeks before enrolling, unless you have specific progression criteria. Additionally, you must not have taken any myelosuppressive agents within 30 days of enrollment.

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

Research has shown that using docetaxel and radium-223 together can be safe for treating prostate cancer that has spread to the bones. In one study, patients first received radium-223 followed by chemotherapy, including docetaxel, and most tolerated these treatments well. Another study found that this combination helped slow cancer growth and lower certain cancer markers in the blood.

Before using this combination, doctors must determine the safest dose. This process involves testing different amounts to identify the most effective dose with minimal side effects. While studies suggest this combination is generally well-tolerated, the current trial continues to seek the optimal dose that balances effectiveness and safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about docetaxel combined with Radium 223 for prostate cancer because it offers a unique double attack on cancer cells. Unlike standard treatments that primarily use hormone therapy or chemotherapy alone, this combination leverages docetaxel's ability to disrupt cell division alongside Radium 223's targeted radiation delivery to bone metastases. This dual approach not only aims to directly kill cancer cells but also potentially improves outcomes for patients with advanced prostate cancer. The ability to precisely target bone metastases with Radium 223 is particularly promising, as bone is a common site for prostate cancer spread.

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

This trial will evaluate the combination of docetaxel and Radium 223 for treating prostate cancer that has spread to the bones. Research has shown that using docetaxel with Radium 223 can help treat this condition. In one study, patients lived without their cancer worsening for an average of 11.7 months and lived for an average of 20.1 months overall. Another study found that out of 31 patients, one had a complete response, five had partial responses, and 23 had stable disease, meaning their cancer did not worsen. These results suggest that this combination treatment may help slow cancer growth and extend life for some patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Paul Mathew, MD

Principal Investigator

Tufts Medical Center

Are You a Good Fit for This Trial?

This trial is for men over 18 with advanced prostate cancer that's resistant to hormone therapy. They must have a good level of blood cells, no severe liver issues, and at least two bone metastases. Men should be on ongoing castration treatment and agree to use birth control if applicable. Those with certain lung or liver metastases, neuroendocrine differentiation, severe neuropathy, other cancers needing treatment, brain metastases or bad reactions to docetaxel can't join.

Inclusion Criteria

My prostate cancer is spreading despite treatments to lower testosterone.

Hemoglobin > 10 g/dL

Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures.

Exclusion Criteria

I have moderate to severe nerve damage in my hands or feet.

I am currently being treated for another type of cancer.

I haven't taken antiandrogen therapy in the last 4 weeks, or if I did, it didn't work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in

4-week lead-in period with docetaxel monotherapy to assess for docetaxel intolerance

4 weeks

Treatment

Combination therapy with Ra-223 every 4 weeks for 6 cycles in a dose-escalation design

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Radium 223

Trial Overview The study tests the safest high dose of Radium-223 combined with split doses of Docetaxel in men with advanced prostate cancer. It aims to find the best dose for future patients by starting low and gradually increasing it across participants until they reach a limit due to side effects.

How Is the Trial Designed?

Group I: Dose expansion Experimental Treatment 2 Interventions

If the maximum tolerated dose (MTD) of docetaxel is found in arm 1, this dose level will be expanded to include an additional 25 subjects to confirm the safety and explore the preliminary anti-cancer effect. If the MTD is not identified, the study will be stopped and the expansion cohort will not be accrued.

Group II: Dose escalation Experimental Treatment 2 Interventions

There are four dose cohorts (1, 1a, 2, 2a) in this arm and two dose levels of docetaxel (40mg/m\^2 \[level 1\] and 50mg/m\^2 \[level 2\]). Dosing of Radium 223 remains the same in all cohorts (55 KBq/kg given every 28 days for 6 cycles). Maximum tolerated dose (MTD) of docetaxel will be assessed. MTD is defined as the highest dose-level, among those tested, associated with a rate of less than a 33% dose limiting toxicity (DLT).

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Tufts Medical Center

Lead Sponsor

Trials

264

Recruited

264,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Lahey Clinic

Collaborator

Trials

74

Recruited

245,000+

Henry Ford Hospital

Collaborator

Trials

27

Recruited

7,400+

Ohio State University Comprehensive Cancer Center

Collaborator

Trials

350

Recruited

295,000+

Published Research Related to This Trial

Docetaxel shows a 42% response rate in treating androgen-independent prostate cancer based on four Phase II studies, indicating its significant efficacy as a single-agent therapy.

Combining docetaxel with estramustine may enhance response rates but also increases toxicity, and ongoing Phase III studies are expected to clarify the best use of docetaxel in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. Beer, TM., El-Geneidi, M., Eilers, KM.[2018]

In a study involving 921 patients with castration-resistant prostate cancer and symptomatic bone metastases, radium-223 significantly improved health-related quality of life (QOL) compared to placebo, with 29.2% of patients experiencing meaningful improvement in QOL scores versus 18.5% in the placebo group.

Radium-223 not only enhanced survival rates but also resulted in a slower decline in QOL over time, indicating that it provides both therapeutic and quality of life benefits for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. Nilsson, S., Cislo, P., Sartor, O., et al.[2022]

Radium-223 significantly improved overall survival in patients with castration-resistant prostate cancer and symptomatic bone metastases, regardless of whether they had previously received docetaxel treatment, indicating its broad efficacy.

While radium-223 was generally well tolerated, patients with prior docetaxel treatment experienced a higher incidence of severe adverse events, particularly thrombocytopenia, suggesting that previous chemotherapy may influence safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Hoskin, P., Sartor, O., O'Sullivan, JM., et al.[2022]

In a study of 36 patients with castration-resistant prostate cancer and bone metastasis, using Radium-223 (Ra-223) therapy before docetaxel (DOC) resulted in a significantly higher treatment completion rate (94% vs. 52%) and longer progression-free survival (8 months vs. 5 months).

Patients receiving Ra-223 before DOC also experienced longer cause-specific survival (32 months vs. 15 months), suggesting that Ra-223 is more effective and potentially safer when administered prior to DOC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Radium-223 for Castration-resistant Prostate Cancer With Bone Metastasis Before and After Docetaxel. Okabe, KO., Terada, N., Shirakawa, T., et al.[2022]

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

The combination of radium-223 and docetaxel was found to be well tolerated in patients with bone-predominant metastatic castration-resistant prostate cancer, with a recommended phase 2 dose established for future studies.

Patients receiving the combination treatment showed a longer median time to progression of prostate-specific antigen levels compared to those on docetaxel alone, suggesting enhanced antitumor activity from the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial. Morris, MJ., Loriot, Y., Sweeney, CJ., et al.[2020]

In a study of 25 patients with advanced androgen-independent prostate cancer, docetaxel at a higher dose of 100 mg/m showed a 52% overall PSA response rate, with 60% of patients experiencing pain relief.

Despite its efficacy, the treatment had a significant toxicity profile, including severe neutropenia in 76% of patients, indicating that while docetaxel is effective, its use should be cautious and not routine due to the high risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of higher dose docetaxel in androgen-independent prostate cancer. Laber, DA., Glisson, SD., Hargis, JB., et al.[2018]

Docetaxel, an FDA-approved chemotherapy for various cancers, can cause severe side effects, including life-threatening reactions such as anaphylaxis and cardiac-respiratory arrest, as demonstrated in a case involving a 62-year-old patient with metastatic prostate cancer.

Despite premedication with corticosteroids, the patient experienced a cardiac-respiratory arrest within 15 minutes of receiving docetaxel, highlighting the need for careful monitoring during treatment, especially in patients with pre-existing conditions like atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-induced cardiac-respiratory arrest in a patient with chronic atrial fibrillation. Huq, M., Balvanz, TM., Mambourg, S.[2019]

In a study of 47 men with metastatic castration-resistant prostate cancer (mCRPC), combining androgen deprivation therapy (ADT) with docetaxel chemotherapy (DTX) significantly improved radiographic progression-free survival (rPFS) compared to DTX alone, with median rPFS of 9.0 months versus 6.0 months.

While overall survival (OS) was similar between the two groups (42.0 months for DTX+ADT and 38.0 months for DTX), the study indicates that concurrent ADT with DTX is a beneficial strategy for improving disease control in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. Jang, HS., Koo, KC., Cho, KS., et al.[2018]

In a Phase I study involving 18 patients with high-risk prostate cancer, the addition of weekly docetaxel chemotherapy at a safe dose of 20 mg/m² to high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) was found to be safe, with no severe toxicities reported.

At a median follow-up of 2.2 years, the treatment resulted in a high biochemical progression-free survival rate of 94%, indicating promising efficacy for this triple-therapy regimen in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. Chen, RC., Rosenman, JG., Hoffman, LG., et al.[2019]

Docetaxel-based therapy has been shown to provide a survival benefit for men with metastatic prostate cancer, marking a significant advancement beyond palliative care options.

Ongoing trials are exploring various combination therapies with docetaxel, but the best timing for initiating treatment remains unclear due to a lack of prospective clinical trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Petrylak, DP.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40383703/

Dose-Dense Docetaxel and Radium-223 in Bone ... We hypothesized that dose-dense docetaxel with standard radium-223 would be a feasible, safe and effective combination in bone-dominant metastatic CRPC.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1558767325000692

Dose-Dense Docetaxel and Radium-223 in Bone ... Median progression-free survival was 11.7 months, and median overall survival was 20.1 months. Conclusions. A lead-in cycle and a dose-dense schedule of ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5049

Fractionated docetaxel (D) and radium 223 (Ra223) in ... Of 31 pts with evaluable data, best response (RECIST 1.1) was 1 CR, 5 PR, 23 SD, 2 PD. Median PFS was 50.0 weeks (95% CI: 37.3-86.1) and OS was ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03574571

NCT03574571 | A Study to Test Radium-223 With ... The purpose of this study is to compare any good and bad effects of using radium-223 along with docetaxel chemotherapy treatment versus using docetaxel ...

5. targetedonc.com targetedonc.com/view/sequencing-matters-giving-radium-223-prior-to-docetaxel-leads-to-improved-hrqol-tolerability-in-mcrpc

Sequencing Matters: Giving Radium-223 Prior to Docetaxel ... The RAPSON trial found that receiving radium-223 prior to docetaxel in patients with metastatic castration-resistant prostate cancer improved quality of life ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38340349/

Safety and effectiveness of the radium-223-taxane ... Results: Following radium-223 therapy, 182 patients received docetaxel (172 [95%]) and/or cabazitaxel (44 [24%]); 34 patients (19%) received ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS5091

A phase III trial of docetaxel versus docetaxel and radium- ... The combination appeared to have improved declines in prostate specific antigen (PSA) and bone markers, delayed PSA progression, and was better ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03737370

NCT03737370 | Fractionated Docetaxel and Radium 223 ... The objective of this study is to determine the maximum safe dose of Ra-223 in combination with fractionated (split doses) docetaxel when given to subjects ...