Androgen Ablation Therapy + Chemotherapy for Prostate Cancer

(CHAARTED Trial)

Recruiting at 342 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Androgen-deprivation therapy

Must not be taking: 5-alpha reductase inhibitors

Disqualifiers: PSA progression, Prior malignancy, Neuropathy, Cardiac disease, Prior chemotherapy, 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: Unknown

Duration: 18 weeks

790 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen ablation therapy may stop the adrenal glands from making androgens. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether androgen-ablation therapy is more effective with or without docetaxel in treating metastatic prostate cancer. PURPOSE: This randomized phase III trial is studying androgen-ablation therapy and chemotherapy to see how well they work compared to androgen-ablation therapy alone in treating patients with metastatic prostate cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, concurrent antiandrogen therapy is allowed, but not as the only hormonal therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Androgen-deprivation therapy plus chemotherapy for prostate cancer?

Research shows that combining androgen-deprivation therapy with chemotherapy can improve survival in patients with hormone-sensitive metastatic prostate cancer. Additionally, androgen ablation (reducing male hormones) alongside radiotherapy has been shown to provide benefits beyond radiotherapy alone for patients with a poor prognosis. ^{1 2 3 4 5}

Is androgen ablation therapy plus chemotherapy safe for humans?

Androgen ablation therapy, often used for prostate cancer, can have side effects like decreased overall health and quality of life, and may increase the risk of anemia (a condition where you don't have enough healthy red blood cells). These treatments have been studied for safety, but it's important to discuss potential risks with your doctor. ^{6 7 8 9 10}

How is the treatment Androgen-deprivation therapy combined with chemotherapy unique for prostate cancer?

This treatment is unique because it combines androgen-deprivation therapy (which reduces male hormones that can fuel prostate cancer) with chemotherapy, and is most effective when both are started early and simultaneously. This combination can enhance the effectiveness of each treatment more than when they are used separately, potentially improving survival rates. ^{1 3 11 12 13}

Research Team

Christopher Sweeney, MBBS

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for men with metastatic prostate cancer who have not been on androgen-deprivation therapy for more than 120 days. They should be in good enough health to participate, as indicated by specific blood counts and organ function tests. Men must agree to use contraception, and they can't join if they've had certain other cancers or heart problems, severe allergies to docetaxel components, or prior hormone therapy in the metastatic setting.

Inclusion Criteria

PS 2 eligible only if decline in PS is due to metastatic prostate cancer

Platelet count ≥ 100,000/mm^3

More than 30 days (or 6 half-lives) (whichever is longer) since prior participation in another clinical trial

Exclusion Criteria

Prior hormone therapy in the metastatic setting

Active cardiac disease, including the following:

Prior malignancy in the past 5 years except for basal cell or squamous cell carcinoma of the skin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive androgen-deprivation therapy with or without docetaxel chemotherapy. Docetaxel is administered intravenously every 21 days for up to 6 courses.

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up includes assessments every 3 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter.

Up to 10 years

Treatment Details

Interventions

• Androgen-deprivation therapy
• Docetaxel

Trial Overview The study is testing whether adding chemotherapy (docetaxel) to standard hormone treatment (androgen-ablation therapy) improves outcomes for men with advanced prostate cancer. Participants are randomly assigned to receive either both treatments or just the hormonal therapy alone.

Participant Groups

Group I: Androgen-Deprivation Therapy and Docetaxel Experimental Treatment 2 Interventions

Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone \[LHRH\] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group II: Androgen-Deprivation Therapy alone Active Control 1 Intervention

Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone \[LHRH\] agonist therapy, LHRH antagonist therapy, or surgical castration) alone.

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 548 men with prostate cancer, both primary androgen-deprivation therapy (PADT) and salvage medical ADT (SADT) were found to prolong overall survival (OS) and disease-specific survival (DSS), but there was no significant difference in survival outcomes between the two treatment groups.

Most deaths in the study were due to causes unrelated to prostate cancer, suggesting that while ADT can extend survival, its impact on prolonging life specifically from cancer may be limited, especially in patients who progress to hormone-refractory prostate cancer (HRPC), which significantly worsens survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in men receiving androgen-deprivation therapy as primary or salvage treatment for localized or advanced prostate cancer: 20-year single-centre experience. DiBlasio, CJ., Malcolm, JB., Hammett, J., et al.[2013]

Combination hormonal therapy, which achieves 'total androgen blockade,' has shown superior efficacy compared to monotherapy in treating patients with low-tumor-burden metastatic prostate cancer.

Emerging phase II studies indicate that this combination therapy may also benefit patients with locally advanced prostate cancer by prolonging disease-free survival, with ongoing phase III trials to further evaluate its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal Therapy for Prostate Cancer: When to Use It. Einstein, AB.[2019]

References

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

Chemotherapy for localized, high-risk prostate cancer. [2006]

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

Survival outcomes in men receiving androgen-deprivation therapy as primary or salvage treatment for localized or advanced prostate cancer: 20-year single-centre experience. [2013]

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

Combined modality treatment for prostate cancer: role of chemotherapy. [2019]

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

Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials. [2018]

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

Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. [2022]

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

Complications of androgen deprivation therapy in prostate cancer. [2009]

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

Hormonal Therapy for Prostate Cancer: When to Use It. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

A phase II trial of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for local failures or advanced prostate cancer. [2021]

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

Androgen Deprivation Therapy and the Risk of Anemia in Men with Prostate Cancer. [2022]

10. Spain pubmed.ncbi.nlm.nih.gov

External beam radiation therapy for clinically localized prostate cancer: when and how we optimize with concurrent hormonal deprivation. [2011]

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

The timing of androgen ablation therapy and/or chemotherapy in the treatment of prostatic cancer. [2019]

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

Mitoxantrone in patients with prostate specific antigen progression after local therapy for prostate carcinoma. [2019]

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

Rationale for the Radiation Therapy Oncology Group Study RTOG P-0014. [2020]