Platinum and Taxane Chemo for Prostate Cancer

(OPTION-DDR Trial)

Recruiting at 4 trial locations

Overseen By Mariam Jafri

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Canadian Cancer Trials Group

Must be taking: ARPI

Must not be taking: Platinum chemotherapy

Disqualifiers: Symptomatic brain metastasis, Uncontrolled illness, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

Duration: Until disease progression

236 Participants Needed

Trial Summary

What is the purpose of this trial?

The usual approach for most patients who are not in a study is treatment with docetaxel. This study is being done to answer the following question: Can the chance of prostate cancer growing or spreading be lowered by adding a drug to the usual approach? This study is being done to find out if this approach is better or worse than the usual approach for prostate cancer. The usual approach is defined as the care most people get for prostate cancer.

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

The trial requires a 'washout period' (time without taking certain medications) for some treatments, which is the longest of two weeks, 5 half-lives for investigational agents, or the standard cycle length of standard therapies. You should discuss your specific medications with the trial team to see if they need to be stopped.

What data supports the effectiveness of the drug combination of Carboplatin and Docetaxel for prostate cancer?

Research shows that Docetaxel, a component of the treatment, has been effective in extending survival in advanced prostate cancer and has shown promise in high-risk localized cases. Additionally, combining Carboplatin with taxanes like Docetaxel may enhance benefits, especially in castration-resistant prostate cancer. ^{1 2 3 4 5}

Is the combination of docetaxel and carboplatin generally safe for humans?

Docetaxel and carboplatin have been used in various cancer treatments, including prostate cancer. While they can be effective, they may cause serious side effects like anaphylactic reactions (severe allergic reactions), febrile neutropenia (low white blood cell count with fever), and fluid retention. However, in some studies, the combination was found to be less toxic when administered weekly compared to every three weeks. ^{6 7 8 9 10}

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

The combination of carboplatin and docetaxel is unique for treating prostate cancer because it combines the moderate single-agent activity of carboplatin with the proven survival benefits of docetaxel, potentially offering enhanced efficacy for patients with castration-resistant prostate cancer, especially those who have not responded to standard treatments. ^{1 5 9 11 12}

Research Team

Michael Kolinsky

Principal Investigator

Cross Cancer Institute, Edmonton, Alberta, Canada

Eligibility Criteria

This trial is for men with advanced prostate cancer that has spread and doesn't respond to hormone therapy. They must have had prior treatment with drugs like abiraterone or enzalutamide, no small cell carcinoma presence, and be past major surgeries by at least 28 days. Men can't join if they've taken investigational agents recently or have certain types of neuroendocrine tumors.

Inclusion Criteria

My cancer has spread, confirmed by scans within the last 28 days.

My prostate cancer is adenocarcinoma without any neuroendocrine or small cell features.

I have been treated with medications like abiraterone or enzalutamide before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either docetaxel or carboplatin in addition to docetaxel, with monitoring by CT scans and bone scans every 9 weeks, and blood tests every 3 weeks

Until disease progression

CT scans and bone scans every 9 weeks, blood tests every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with continued scans and tests until disease progression, and phone contact every 3 months for life

5.25 years

CT scans and bone scans every 9 weeks, blood tests every 3 weeks, phone contact every 3 months

Treatment Details

Interventions

• Carboplatin
• Docetaxel

Trial Overview The study tests whether adding Carboplatin to the usual Docetaxel chemotherapy lowers the chance of prostate cancer growing or spreading. It compares this combination against the standard treatment alone to see which is more effective in controlling the disease.

Participant Groups

Group I: Carboplatin + Docetaxel Experimental Treatment 2 Interventions

Group II: Docetaxel Active Control 1 Intervention

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

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]

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-based treatments have shown effectiveness in managing advanced, androgen-independent prostate cancer, achieving significant palliative responses and reducing PSA levels by over 50% in patients.

Ongoing phase III trials are expected to provide crucial data on the impact of docetaxel on overall survival, while preliminary studies suggest that combining docetaxel with other novel agents is safe and may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the integrated management of prostate cancer. Current applications and future promise. Logothetis, CJ.[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]

In a study of 310 patients with castration-resistant prostate cancer (CRPC), the combination of taxane-estramustine-carboplatin (TEC) chemotherapy resulted in a significant prostate-specific antigen (PSA) response rate of 69%.

The 12-month survival estimate for patients receiving TEC chemotherapy was 79%, which is notably higher than the median predicted survival of 59%, indicating that TEC may provide substantial clinical benefits in CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials. Regan, MM., O'Donnell, EK., Kelly, WK., et al.[2021]

In a pilot study of 15 patients with hormone-refractory prostate cancer resistant to paclitaxel-based chemotherapy, docetaxel (DTX) showed activity, with 33.3% of patients experiencing a 50% or greater reduction in prostate-specific antigen levels.

Despite its effectiveness, DTX treatment was associated with significant toxicities, including severe anemia in 66.7% of patients, highlighting the need for further research to optimize treatment regimens and manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study. Urakami, S., Yoshino, T., Kikuno, N., et al.[2018]

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 15 patients with metastatic castration-resistant prostate cancer (mCRPC), docetaxel combined with carboplatin showed promising short-term efficacy, with 66.7% of patients experiencing a PSA decline of over 50%.

The treatment was generally well-tolerated, with most adverse reactions, such as bone marrow suppression and gastrointestinal issues, being manageable, indicating a favorable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer]. Bai, GC., Song, Y., Jin, J., et al.[2022]

In a study involving 10 patients with hormone-refractory prostate cancer, weekly docetaxel-based chemotherapy showed a significant reduction in serum prostate-specific antigen (PSA) levels, with 90% of patients experiencing a decrease of 50% or more.

Weekly docetaxel-based chemotherapy was found to be as effective as triweekly chemotherapy while demonstrating lower toxicity, making it a suitable first-line treatment option for elderly patients or those with poor health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with weekly paclitaxel or docetaxel, carboplatin, and estramustine for hormone-refractory prostate cancer. Yasufuku, T., Shigemura, K., Matsumoto, O., et al.[2018]

Carboplatin and paclitaxel (CP) demonstrated moderate efficacy in treating castration-resistant prostate cancer (CRPC), particularly as a first-line treatment, with a 55.6% PSA response rate and a median overall survival of 19 months for patients receiving it first.

In contrast, CP showed limited effectiveness in the third-line setting, with only a 10% PSA response rate and a median overall survival of 6 months, suggesting it may be more beneficial for patients with specific genetic mutations, like BRCA2 defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer. Fujiwara, M., Akamatsu, S., Sumiyoshi, T., et al.[2020]

Recent reviews indicate that platinum-based chemotherapy, particularly carboplatin, can be effective in treating metastatic hormone-refractory prostate cancer (HRPC), especially when combined with other agents like taxanes and estramustine.

Next-generation platinum drugs, such as satraplatin, show promise in improving progression-free survival in HRPC patients, suggesting a potential new avenue for treatment, particularly for those who have progressed after standard docetaxel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for platinum chemotherapy in the treatment of patients with hormone-refractory prostate cancer? Oh, WK., Tay, MH., Huang, J.[2007]

References

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

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

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

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

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

Docetaxel in the integrated management of prostate cancer. Current applications and future promise. [2018]

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

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

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

Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials. [2021]

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

Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study. [2018]

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. China pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer]. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with weekly paclitaxel or docetaxel, carboplatin, and estramustine for hormone-refractory prostate cancer. [2018]

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

Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer. [2020]

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

Is there a role for platinum chemotherapy in the treatment of patients with hormone-refractory prostate cancer? [2007]