Berzosertib + Carboplatin +/- Docetaxel for Prostate Cancer

Recruiting at 24 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: LHRH agonists

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Brain metastases, Uncontrolled illness, 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

Compensation: Varies

Number of Visits: 21

Duration: Up to 2 years

73 Participants Needed

Trial Summary

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

The trial requires that you stop taking any oral anti-cancer medications at least 14 days before starting the study treatment. Additionally, you must discontinue any ototoxic or nephrotoxic medications at least 7 days before the first dose of carboplatin. If you are taking medications that strongly affect the enzyme CYP3A4, you will need to avoid them during the trial.

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

Research shows that Docetaxel, a component of the combination, is effective in extending survival and reducing pain in advanced prostate cancer. Additionally, combining Carboplatin with taxanes like Docetaxel may enhance treatment benefits for certain prostate cancer patients. ^{1 2 3 4 5}

Is the combination of Berzosertib, Carboplatin, and Docetaxel safe for humans?

Docetaxel, when used in combination with other drugs like carboplatin, has been studied in prostate cancer patients and is generally considered safe, though it can have side effects. These side effects can include fatigue, low blood cell counts, and nausea, but they are usually manageable with medical support. ^{1 2 6 7 8}

What makes the drug combination of Berzosertib, Carboplatin, and Docetaxel unique for prostate cancer?

This drug combination is unique because it includes Berzosertib, which is a novel agent that targets DNA repair mechanisms, potentially enhancing the effectiveness of traditional chemotherapy drugs like Carboplatin and Docetaxel. This approach may offer a new way to treat prostate cancer, especially in cases where the cancer is resistant to hormone therapy. ^{2 9 10 11 12}

What is the purpose of this trial?

This phase II trial studies how well berzosertib (M6620) and carboplatin with or without docetaxel works in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). M6620 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and docetaxel, 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. Giving M6620, carboplatin and docetaxel may work better in treating patients with metastatic castration-resistant prostate cancer compared to carboplatin and docetaxel alone.

Research Team

Atish D Choudhury

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

This trial is for men with metastatic castration-resistant prostate cancer that has progressed despite previous treatments. Participants must have a low testosterone level, adequate organ function, and no severe side effects from past cancer therapies. They should not have brain metastases or active infections and must not be on certain drugs that could interact with the study medication.

Inclusion Criteria

My prostate cancer is confirmed and getting worse.

My cancer has spread, shown by scans, and I have low testosterone levels.

I have previously been treated with mTOR inhibitors, TKIs, or biologic therapies.

Exclusion Criteria

I have been treated with platinum-based drugs or ATR inhibitors for prostate cancer.

I am on medication that could harm my hearing or kidneys and cannot stop taking it.

I do not have any uncontrolled illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either docetaxel and carboplatin or carboplatin and berzosertib. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30-42 days

Treatment Details

Interventions

• Berzosertib (M6620)
• Carboplatin
• Docetaxel

Trial Overview The trial is testing the effectiveness of berzosertib (M6620) combined with carboplatin, with or without docetaxel, in treating advanced prostate cancer. Berzosertib blocks enzymes needed for cell growth while carboplatin and docetaxel are chemotherapy drugs aiming to kill or stop the spread of tumor cells.

Participant Groups

Group I: Arm B (carboplatin, berzosertib) Experimental Treatment 3 Interventions

Patients receive carboplatin IV over 30 minutes on day 1 and berzosertib IV over 60-90 minutes on days 2 and 9. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (docetaxel, carboplatin) Active Control 3 Interventions

Patients receive docetaxel IV over 60 minutes and carboplatin IV over 30 minutes, or carboplatin alone on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who have PSA progression or radiographic progression may crossover to Arm B.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 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 of 83 Chinese patients with metastatic hormone-refractory prostate cancer, docetaxel plus prednisone showed a higher efficacy compared to mitoxantrone plus prednisone, with 43.2% of patients achieving a complete or partial response versus 33.3% for mitoxantrone.

Docetaxel plus prednisone also provided better PSA control, with an average time to PSA progression of 37.8 weeks compared to 25.3 weeks for mitoxantrone, although it was associated with slightly higher toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel plus prednisone versus mitoxantrone plus prednisone for metastatic hormone-refractory prostate cancer in Chinese patients: experience of a single center. Zhang, HL., Ye, DW., Yao, XD., et al.[2018]

Docetaxel has shown significant effectiveness as a single agent in treating hormone refractory prostate cancer, achieving a 42% prostate-specific antigen response rate in four phase-II studies.

Combining docetaxel with estramustine may enhance the response rate, but it also increases the risk of toxicity, and further evaluation in ongoing phase-III studies will clarify its overall role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Significance of docetaxel in the chemotherapy of hormone-refractory prostate cancer]. Wolff, JM.[2018]

References

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

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

2. 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]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Characterization of prognostic factors and efficacy in a phase-II study with docetaxel and estramustine for advanced hormone refractory prostate cancer. [2018]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Phase-II study of docetaxel, estramustine phosphate, and carboplatin in patients with hormone-refractory prostate cancer. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Docetaxel plus prednisone versus mitoxantrone plus prednisone for metastatic hormone-refractory prostate cancer in Chinese patients: experience of a single center. [2018]

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

Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

Outcome, clinical prognostic factors and genetic predictors of adverse reactions of intermittent combination chemotherapy with docetaxel, estramustine phosphate and carboplatin for castration-resistant prostate cancer. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

[Significance of docetaxel in the chemotherapy of hormone-refractory prostate cancer]. [2018]

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

Phase II trial evaluating a docetaxel-capecitabine combination as treatment for hormone-refractory prostate cancer. [2018]