Carboplatin Before Surgery for Prostate Cancer

Recruiting at 131 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Southwest Oncology Group

Disqualifiers: Metastatic disease, Prior pelvic RT, Other malignancy, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well carboplatin before surgery works in treating patients with high-risk prostate cancer and an inherited BRCA1 or BRCA2 gene mutation. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping, or slowing the growth of tumor cells. Giving carboplatin before surgery may shrink tumors in patients with high-risk prostate cancer with BRCA1 and BRCA2 gene mutations.

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

The trial does not specify if you need to stop taking your current medications. However, if you are on certain prostate cancer treatments like gnRH agonists or anti-androgens, you can continue them if their effects don't last beyond one month after joining the study.

What data supports the effectiveness of the drug carboplatin before surgery for prostate cancer?

Research shows that carboplatin has moderate activity in treating prostate cancer, with 17% of patients experiencing a partial response and 50% having disease stabilization. Additionally, carboplatin is known to be effective in other cancers like ovarian and breast cancer, and it is less toxic than similar drugs like cisplatin. ^{1 2 3 4 5}

Is carboplatin generally safe for humans?

Carboplatin is generally considered safe for humans, with milder side effects compared to similar drugs like cisplatin. It does not cause kidney damage at normal doses and is less likely to cause nerve or hearing problems. However, it can cause a decrease in blood cells, which may lead to increased risk of infection or bleeding. ^{6 7 8 9 10}

How is the drug carboplatin unique in treating prostate cancer?

Carboplatin is unique in treating prostate cancer because it is a platinum-based drug that is less toxic than its predecessor, cisplatin, and is being explored for use before surgery to potentially improve outcomes. It is typically used in combination with other drugs for patients who have already been heavily treated with other therapies. ^{1 11 12 13 14}

Research Team

Heather H Cheng

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for men over 18 with high-risk prostate cancer and a BRCA1 or BRCA2 gene mutation. They should have advanced cancer (stage cT3a - cT4x, Gleason sum 8-10) and a PSA level over 20 ng/mL. Participants can be on certain hormone treatments but must not extend beyond one month after joining the study.

Inclusion Criteria

My prostate cancer is high grade (Gleason score 8-10).

My cancer is classified between stages cT3a to cT4x.

I can take care of myself and am up and about more than 50% of my waking hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carboplatin intravenously before undergoing surgery

6-8 weeks

Surgery

Participants undergo surgery after receiving neoadjuvant carboplatin

1 week

Follow-up

Participants are monitored for PSA progression and other outcomes post-surgery

Up to 5 years

Treatment Details

Interventions

• Carboplatin
• Surgical Procedure

Trial Overview The trial is testing if giving Carboplatin, a platinum-containing chemotherapy drug, before surgery can shrink tumors in patients with high-risk prostate cancer who also carry the inherited BRCA gene mutations.

Participant Groups

Group I: Treatment (carboplatin) Experimental Treatment 7 Interventions

Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.

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?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Carboplatin, introduced in 1981, has shown to be as effective as cisplatin in treating ovarian cancer while being considerably less toxic, making it a safer alternative for patients.

Current clinical studies suggest that carboplatin may expand treatment options for various cancers, including acute leukemia, endometrial cancer, and breast cancer, particularly when combined with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of carboplatin: replacing, complementing, and extending the therapeutic horizons of cisplatin. Muggia, FM.[2018]

In a phase II study involving 50 patients with locally advanced or metastatic breast cancer, the combination of pemetrexed and carboplatin showed a promising overall response rate of 54%, with a median response duration of 11.1 months.

The treatment was associated with manageable safety concerns, primarily hematologic toxicities, including grade 3/4 neutropenia in 58% of patients, but no severe non-hematologic toxicities were reported, indicating an acceptable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. Garin, A., Manikhas, A., Biakhov, M., et al.[2015]

Carboplatin (CBDCA) has shown similar effectiveness to cisplatin in treating various cancers, including head and neck and ovarian cancers, while demonstrating significantly lower toxicity, particularly in terms of renal effects and side effects like nausea and vomiting.

In clinical trials, carboplatin's dose-limiting factor was myelosuppression, making it a safer alternative to cisplatin, which has more severe side effects, thus positioning carboplatin as a valuable option in cancer chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of carboplatin]. Tsukagoshi, S.[2013]

In a study of 25 patients with metastatic prostate cancer who had progressed after hormonal treatment, weekly administration of carboplatin showed moderate efficacy, with 17% of patients achieving a partial response and 50% experiencing disease stabilization.

The treatment was manageable in terms of toxicity, primarily causing myelosuppression, even in elderly patients with extensive bone metastases, and the median response duration was 7 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in advanced hormone refractory prostatic cancer patients. Canobbio, L., Guarneri, D., Miglietta, L., et al.[2019]

In a pilot phase II trial involving 46 patients with localized nonsquamous NSCLC, the combination of pemetrexed and carboplatin as neoadjuvant therapy was found to be feasible, with 40 patients completing the treatment and 27 undergoing successful surgical resection.

The estimated 3-year survival rate for all participants was 46%, and while the treatment's toxicity was consistent with previous reports, 41% of patients did not proceed to surgery, indicating the need for further research to optimize this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of preoperative pemetrexed plus carboplatin in patients with stage IB-III nonsquamous non-small cell lung cancer (NSCLC). Hainsworth, JD., Waterhouse, DM., Shih, KC., et al.[2019]

In a study of 114 dogs treated with carboplatin, a non-haematological toxicity rate of 19.3% was observed, indicating that while carboplatin is generally well-tolerated, some dogs can experience side effects.

This case report highlights the first instance of cutaneous delayed-hypersensitivity to carboplatin in a dog, which was successfully managed with antihistamines and adjustments to future treatments, ensuring no further reactions occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probable cutaneous hypersensitivity to carboplatin single-agent chemotherapy in a dog. Lanore, D., Sayag, D.[2013]

In a study of 42 patients with advanced seminoma, 71% achieved complete remission with carboplatinum treatment, indicating it is an effective option for this type of cancer.

Carboplatinum therapy showed mild toxicity with no neurotoxicity or nephrotoxicity, suggesting it may be a safer alternative to traditional cisplatin-based chemotherapy, especially for patients with lymph node metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent carboplatinum for advanced seminoma. A phase II study. Schmoll, HJ., Harstrick, A., Bokemeyer, C., et al.[2019]

Carboplatin, used as a single-agent chemotherapy, effectively treated a 36-year-old man with stage IIB seminoma, leading to normalization of tumor markers and significant reduction in tumor size after 4 courses.

The treatment was associated with milder toxicity compared to traditional cisplatin-based therapies, with no severe side effects such as renal damage, nausea, or neuropathy, and the patient remained disease-free 9 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of advanced seminoma treated effectively with single agent carboplatin therapy]. Fukuzawa, S., Yu, A., Hashimura, T., et al.[2013]

A phase I trial involving 33 patients tested the combination of cisplatin and carboplatin, revealing that while the combination is feasible, it can lead to unexpectedly severe thrombocytopenia (low platelet count) when using specific doses, particularly 280 mg/m2 carboplatin with 25 mg/m2 cisplatin.

Despite the risk of thrombocytopenia, the combination therapy showed promising responses in tumors known to be responsive to platinum-based treatments, suggesting that further investigation into this combination is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. Trump, DL., Grem, JL., Tutsch, KD., et al.[2017]

A meta-analysis of 12 randomized controlled trials involving 2,048 patients found no significant difference in overall survival between carboplatin and cisplatin-based chemotherapy for advanced non-small cell lung cancer (NSCLC).

While cisplatin showed a slight advantage in objective response rate, carboplatin had a more favorable toxicity profile, suggesting that the choice of chemotherapy should consider both efficacy and the patient's health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line carboplatin-versus cisplatin-based chemotherapy for non-small cell lung cancer: A meta-analysis. Griesinger, F., Korol, EE., Kayaniyil, S., et al.[2020]

In a Phase II trial involving 15 patients with docetaxel-pretreated castration-resistant prostate cancer, carboplatin plus etoposide demonstrated a median progression-free survival of 11 weeks and a median overall survival of 18 weeks, suggesting some therapeutic activity after multiple prior treatments.

Out of seven patients with measurable disease, two experienced a partial response and two had stable disease, indicating that carboplatin and etoposide may provide clinical benefits even in patients who have failed all currently approved therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus etoposide in heavily pretreated castration-resistant prostate cancer patients. Buonerba, C., Federico, P., Bosso, D., et al.[2014]

In a study of 43 patients with metastatic castration-resistant prostate cancer, the combination of carboplatin and paclitaxel resulted in a prostate-specific antigen response in 42% of patients, indicating significant efficacy.

The treatment was well-tolerated, with a median progression-free survival of 115 days and a median overall survival of 8.1 months, suggesting it is a viable option for patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of carboplatin in combination with paclitaxel in patients with castration-resistant prostate cancer. Rusarova, N., Vitaskova, D., Kalabova, H., et al.[2023]

In a study of 11 patients with advanced oesophageal cancer, carboplatin showed a partial response in 9% of patients and minor responses in 2 cases, indicating some level of antitumor activity.

Carboplatin was well tolerated, with only one case of reversible myelosuppression reported, and no nephrotoxicity or vomiting, suggesting it may be a safer alternative to cisplatin in chemotherapy regimens for oesophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in the treatment of oesophageal cancer. Mannell, A., Winters, Z.[2014]

In a Phase II study involving 117 children with drug-resistant solid tumors, carboplatin showed some effectiveness, particularly against Wilms' tumor, Ewing's sarcoma, neuroblastoma, soft tissue sarcoma, and endodermal sinus tumor of the testis.

While myelosuppression (low blood cell counts) was common, carboplatin exhibited low rates of nonhematologic toxicity, such as ototoxicity and nephrotoxicity, making it a potentially safer option compared to its parent compound, cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin in children with recurrent or progressive solid tumors. A report from the Childrens Cancer Group. Ettinger, LJ., Gaynon, PS., Krailo, MD., et al.[2019]

References

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

Overview of carboplatin: replacing, complementing, and extending the therapeutic horizons of cisplatin. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. [2015]

3. Japan pubmed.ncbi.nlm.nih.gov

[Development of carboplatin]. [2013]

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

Carboplatin in advanced hormone refractory prostatic cancer patients. [2019]

5. Ireland pubmed.ncbi.nlm.nih.gov

Phase II trial of preoperative pemetrexed plus carboplatin in patients with stage IB-III nonsquamous non-small cell lung cancer (NSCLC). [2019]

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

Probable cutaneous hypersensitivity to carboplatin single-agent chemotherapy in a dog. [2013]

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

Single-agent carboplatinum for advanced seminoma. A phase II study. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[A case of advanced seminoma treated effectively with single agent carboplatin therapy]. [2013]

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

Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. [2017]

10. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line carboplatin-versus cisplatin-based chemotherapy for non-small cell lung cancer: A meta-analysis. [2020]

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

Carboplatin plus etoposide in heavily pretreated castration-resistant prostate cancer patients. [2014]

12. England pubmed.ncbi.nlm.nih.gov

The role of carboplatin in combination with paclitaxel in patients with castration-resistant prostate cancer. [2023]

13. South Africa pubmed.ncbi.nlm.nih.gov

Carboplatin in the treatment of oesophageal cancer. [2014]

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

A phase II study of carboplatin in children with recurrent or progressive solid tumors. A report from the Childrens Cancer Group. [2019]