Docetaxel + Radium 223 for Prostate Cancer

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

43 Participants Needed

Trial Summary

What is the purpose of this trial?

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 and to determine the best administering dose. The study will look at side effects that may happen while taking the combination treatment. A total of approximately 18 subjects will take part in the dose escalation part of the study and an additional 25 subjects will participate in the expansion cohort. This study will be conducted across four centers in the United States.

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.

What data supports the effectiveness of the drug Docetaxel in treating prostate cancer?

Research shows that Docetaxel improves survival in men with advanced prostate cancer, particularly in cases where the cancer no longer responds to hormone therapy. It has been shown to extend survival and is being tested in combination with other treatments for high-risk patients. ^{1 2 3 4 5}

Is the combination of Docetaxel and Radium 223 safe for prostate cancer treatment?

Docetaxel has been shown to be safe at certain doses when used with radiation therapy for prostate cancer, but it can cause severe side effects like allergic reactions and heart problems. There is no specific safety data available for the combination of Docetaxel and Radium 223. ^{2 4 6 7 8}

How is the drug combination of Docetaxel and Radium 223 unique for treating prostate cancer?

This drug combination is unique because it combines Docetaxel, which targets cancer cells directly, with Radium 223, which specifically targets bone metastases (cancer spread to bones) using alpha particles. This dual approach aims to improve survival by addressing both the tumor and its spread to bones, which is a common issue in advanced prostate cancer. ^{9 10 11 12 13}

Research Team

Paul Mathew, MD

Principal Investigator

Tufts Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. England pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. [2018]

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

Effect of docetaxel in patients with hormone-dependent prostate-specific antigen progression after local therapy for prostate cancer. [2018]

6. England 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. [2019]

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

A phase II study of higher dose docetaxel in androgen-independent prostate cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Docetaxel-induced cardiac-respiratory arrest in a patient with chronic atrial fibrillation. [2019]

9. England 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. [2020]

10. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Radium-223 for Castration-resistant Prostate Cancer With Bone Metastasis Before and After Docetaxel. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. [2022]

12. England 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. [2022]

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

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