Chemotherapy + Hormone Therapy With Surgery for Prostate Cancer

Recruiting at 225 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: LHRH agonists

Disqualifiers: Small cell, Neuroendocrine, Transitional, 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: 6

788 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: 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. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as goserelin and leuprolide, may stop the adrenal glands from making androgens. Giving docetaxel and leuprolide or goserelin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving docetaxel and leuprolide or goserelin before surgery is more effective than surgery alone in treating patients with prostate cancer. PURPOSE: This randomized phase III trial is studying docetaxel and leuprolide or goserelin to see how well they work when given before surgery compared with surgery alone in treating patients with high-risk localized 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, you should not have had prior treatment for prostate cancer, except for up to 4 months of certain hormone therapies. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment combining chemotherapy and hormone therapy with surgery for prostate cancer?

Research suggests that combining hormone therapy with surgery can improve outcomes in localized or locally advanced prostate cancer. Additionally, using chemotherapy earlier in the treatment process, rather than waiting for hormone resistance, may improve survival and quality of life in advanced prostate cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy, hormone therapy, and surgery generally safe for treating prostate cancer?

The combination of chemotherapy, hormone therapy, and surgery for prostate cancer has been studied, and surgery is considered a safe option with improvements in technology. However, hormone therapy can have cardiovascular risks, and chemotherapy may cause fatigue and anemia, so patients should be monitored for these side effects. ^{6 7 8 9 10}

How does the treatment of chemotherapy and hormone therapy with surgery differ for prostate cancer?

This treatment is unique because it combines chemotherapy and hormone therapy with surgery to potentially improve outcomes for prostate cancer patients. Unlike traditional treatments that may use these therapies separately, this approach aims to enhance the effectiveness by using them together, which may help in reducing tumor size and managing symptoms more effectively. ^{11 12 13 14 15}

Research Team

James Eastham, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for men with high-risk localized prostate cancer who are fit for surgery and expected to live more than 10 years. They must have a specific type of prostate cancer (adenocarcinoma), no prior treatments except possibly short-term hormone therapy, and no evidence of spread beyond the prostate. Men with other recent cancers or certain blood clotting events not suitable for surgery can't join.

Inclusion Criteria

I am 18 years old or older.

I am able to get out of my bed or chair and move around.

My cancer is in an early stage and has not spread, as confirmed by scans.

Exclusion Criteria

I have a history of blood clots or stroke and cannot undergo major prostate surgery.

I currently have cancer.

I have not had any cancer except for basal or squamous cell skin cancer in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Participants receive six cycles of docetaxel every 3 weeks combined with 18-24 weeks of androgen deprivation therapy

18-24 weeks

6 visits (in-person) for chemotherapy cycles

Surgical Intervention

Participants undergo standard surgical intervention within 60 days of completing neoadjuvant therapy

2 months

Adjuvant Radiation (optional)

Participants may receive adjuvant external beam radiation initiated within 6 months of surgery

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Treatment Details

Interventions

• Docetaxel
• Goserelin
• Leuprolide
• Surgery

Trial Overview The study is testing if giving chemotherapy drug docetaxel along with hormone therapies leuprolide or goserelin before surgery offers better outcomes compared to just having the surgery alone. The goal is to see if this combination treatment can shrink tumors more effectively, making them easier to remove surgically.

Participant Groups

Group I: Arm B: surgical intervention Experimental Treatment 1 Intervention

All patients undergo standard surgical intervention. The surgical procedures will be performed within 60 days of randomization. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. Adjuvant radiation must be initiated within 6 months of the date of surgery.

Group II: Arm A: docetaxel + LHRH agonist + surgical intervention Experimental Treatment 3 Interventions

Patients receive six cycles of docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines. Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

Southwest Oncology Group

Collaborator

Trials

389

Recruited

260,000+

Eastern Cooperative Oncology Group

Collaborator

Trials

272

Recruited

153,000+

SWOG Cancer Research Network

Collaborator

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NCIC Clinical Trials Group

Collaborator

Trials

190

Recruited

145,000+

Findings from Research

Chemotherapy has been shown to provide significant benefits for patients with advanced prostate cancer that no longer respond to hormonal therapy, outperforming traditional palliative and hormonal treatments.

Evidence suggests that combining antitumor agents with hormonal therapy as an initial treatment for metastatic prostate cancer may be more effective than delaying chemotherapy until after hormone failure, especially in patients with poorer prognoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A decade of experience with chemotherapy for prostate cancer. Slack, NH., Murphy, GP.[2019]

A meta-analysis of 15 randomized controlled trials involving 16,795 patients found that novel oral anti-androgens (NOAAs) are associated with a 26% increased risk of all-grade fatigue compared to standard treatments.

Interestingly, NOAAs were linked to a decreased risk of anemia, suggesting that while they may cause fatigue, they do not significantly increase the likelihood of anemia in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Fatigue and Anemia in Patients With Prostate Cancer Treated With Novel Oral Anti-androgens: A Meta-Analysis of Randomized Controlled Trials. Babkoor, AA., Aljabri, Y., Alzubaidi, A., et al.[2022]

References

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

Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. [2022]

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

European trials and the management of prostate cancer. [2019]

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

A decade of experience with chemotherapy for prostate cancer. [2019]

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

Early versus late hormonal therapy: debating the issues. [2019]

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

Does chemotherapy have a role before hormone-resistant disease develops? [2021]

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

Risk of Fatigue and Anemia in Patients With Prostate Cancer Treated With Novel Oral Anti-androgens: A Meta-Analysis of Randomized Controlled Trials. [2022]

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

The evolving role of estrogen therapy in prostate cancer. [2019]

8. China pubmed.ncbi.nlm.nih.gov

[Clinical study of diethylstilbestrol in hormone refractory prostate cancer]. [2013]

9. Turkey pubmed.ncbi.nlm.nih.gov

The role of surgery in high risk and advanced prostate cancer: A narrative review. [2021]

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

[Comparison of hormone therapy alone and in combination with chemotherapy of cisplatin and methotrexate in newly diagnosed patients with stage D2 prostatic cancer]. [2019]

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

Early combined hormonal and chemotherapy for metastatic prostatic carcinoma. [2019]

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

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

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

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

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

Chemotherapy of prostatic cancer. [2013]

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

Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study. [2017]