Bicalutamide + Sunitinib for Kidney Cancer

Overseen By Kirsten Haden

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: State University of New York at Buffalo

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active TB, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks (4 cycles of 21 days each)

28 Participants Needed

Trial Summary

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the drugs Bicalutamide and Sunitinib for kidney cancer?

Research shows that Sunitinib, one of the drugs in the treatment, is effective for kidney cancer, specifically metastatic renal cell carcinoma. It has been shown to improve survival rates and is considered a standard treatment for this type of cancer. ^{1 2 3 4 5}

Is the combination of Bicalutamide and Sunitinib safe for humans?

Sunitinib, used for kidney cancer, has been studied for safety and can cause side effects like high blood pressure, fatigue, and skin changes. Patients often need dose adjustments to manage these side effects. ^{6 7 8 9 10}

How does the drug combination of Bicalutamide and Sunitinib differ from other treatments for kidney cancer?

The combination of Bicalutamide and Sunitinib for kidney cancer is unique because it combines a hormone therapy (Bicalutamide) with a targeted therapy (Sunitinib), which is a tyrosine kinase inhibitor that blocks specific proteins involved in cancer growth. This approach may offer a novel mechanism of action compared to standard treatments that typically use Sunitinib alone. ^{2 10 11 12 13}

What is the purpose of this trial?

This is a Phase I/II open-label, efficacy and safety study of bicalutamide in combination with sunitinib in patients with advanced renal cell carcinoma (RCC) who have been treated with a receptor tyrosine kinase inhibitor (RTKI) and experienced disease progression.

Research Team

Roberto Pili, MD

Principal Investigator

State University of New York at Buffalo

Eligibility Criteria

This trial is for adults with advanced renal cell carcinoma (RCC) who have tried a receptor tyrosine kinase inhibitor but their disease got worse. They need to have measurable disease, be expected to live at least 6 more months, and agree to use contraception. They must also have good organ function and an ECOG performance status of 0-2.

Inclusion Criteria

Have measurable disease based on RECIST 1.1

I have taken a pregnancy test within the last 3 days and it was negative.

Be willing and able to provide written informed consent for the trial

Exclusion Criteria

I am currently being treated for an infection.

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

I have an immune system disorder or have been on steroids or other immune-weakening medicines recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bicalutamide in combination with sunitinib. Sunitinib is dosed at 2 weeks ON and 1 week OFF schedule, with dose modifications allowed. Bicalutamide is administered at 50 mg daily.

12 weeks (4 cycles of 21 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and response by RECIST criteria.

3 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if initial response criteria are met.

Long-term

Treatment Details

Interventions

• Bicalutamide
• Sunitinib

Trial Overview The study tests the safety and effectiveness of combining Bicalutamide with Sunitinib in treating RCC patients resistant to previous RTKI therapy. It's an open-label Phase I/II trial where all participants know they're receiving both drugs.

Participant Groups

Group I: Bicalutamide in combination with Sunitinib Experimental Treatment 1 Intervention

Bicalutamide 50mg once a day (QD) in combination with sunitinib 37.5mg, 25mg or 50mg QD (2 weeks ON, 1 week OFF). Four or more 21 day-long cycles.

Who Is Running the Clinical Trial?

State University of New York at Buffalo

Lead Sponsor

Trials

279

Recruited

52,600+

Findings from Research

In a study of 103 patients with metastatic renal cell cancer, individualized dose escalation of sunitinib significantly improved median progression-free survival (39.7 months) and overall survival (57.5 months) compared to standard dosing (14.2 months and 27.9 months, respectively).

The study found that dose escalation was safe, with common side effects including fatigue, hypertension, stomatitis, and significant weight loss, indicating that increasing sunitinib doses can be a beneficial strategy for patients with slight disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma. Maráz, A., Cserháti, A., Uhercsák, G., et al.[2018]

In a phase III trial involving 750 patients with metastatic renal cell carcinoma (mRCC), sunitinib significantly improved progression-free survival compared to interferon-α, establishing it as a reference standard for first-line treatment.

Sunitinib has a manageable safety profile, with most adverse events being treatable, and ongoing research is exploring its use in combination therapies and as adjuvant or neoadjuvant treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib for the treatment of metastatic renal cell carcinoma. Oudard, S., Beuselinck, B., Decoene, J., et al.[2022]

In a phase II study involving 17 patients with metastatic renal cell carcinoma, 2-methoxyestradiol (2ME2 NCD) showed minimal anti-tumor activity, with no objective responses observed, leading to the study's termination.

The treatment was poorly tolerated, with 35% of patients needing to discontinue therapy due to toxicities, highlighting the need for a new 2ME2 analog that may have a better safety profile and increased effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate. Bruce, JY., Eickhoff, J., Pili, R., et al.[2022]

The 2:1 treatment schedule of sunitinib for metastatic renal cell carcinoma (mRCC) shows a better toxicity profile compared to the standard 4:2 regimen, making it more tolerable for patients.

Current evidence indicates that there are no significant differences in progression-free survival (PFS) or overall survival (OS) between the 2:1 and 4:2 schedules, suggesting that the 2:1 regimen is a viable alternative without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapeutic schedules of Sunitinib: Current evidence regarding the 2:1 scheme.] Puche-Sanz, I., Flores-Martín, JF., Vázquez-Alonso, F., et al.[2018]

Sunitinib can be safely administered to patients with severe renal impairment or those on dialysis, with effective doses ranging from 25-50 mg daily, showing similar efficacy to patients with normal kidney function.

In a study of 19 patients, the median progression-free survival was 43 weeks, and 15 patients achieved either a partial response or stable disease, indicating that sunitinib remains a viable treatment option for metastatic renal cell carcinoma in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis. Josephs, D., Hutson, TE., Cowey, CL., et al.[2022]

Sunitinib has a similar safety profile in patients undergoing nephrectomy for kidney cancer, whether used in the adjuvant setting or for metastatic disease, based on data from phase III trials including CARMENA and SURTIME.

Effective management of sunitinib's adverse effects is crucial, particularly in the adjuvant setting, where maintaining dose intensity and exposure can impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. Heraudet, L., Domblides, C., Daste, A., et al.[2022]

Medical oncologists are more likely to treat patients with metastatic renal cell carcinoma (RCC) using multitargeted tyrosine kinase inhibitors like sunitinib and sorafenib, administering treatment in their own practices rather than in hospitals, as is common among urologists.

Adverse events from these treatments are common, occurring in 53% of patients, with the most frequent issues being fatigue, high blood pressure, diarrhea, and hand-foot skin syndrome, often leading to treatment pauses or stops.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medical treatment of metastatic renal cell carcinoma after the approval and market entry of multitargeted tyrosine kinase inhibitors in Germany]. Bolenz, C., Trojan, L., Honeck, P., et al.[2019]

Sunitinib, an oral tyrosine kinase inhibitor, has shown significant antitumor activity and improved progression-free survival in patients with renal cell carcinoma, based on phase II and III clinical trials.

Understanding the unique side effects of sunitinib is crucial for effective patient education, enabling better anticipation and management of these therapy-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. Schwandt, A., Wood, LS., Rini, B., et al.[2022]

In a study of 34 patients with advanced renal cell carcinoma treated with sorafenib or sunitinib, the median progression-free survival was 8 months, with 34% of patients experiencing disease stabilization and 28% showing a partial response.

The study highlighted that 56% of patients experienced grade 3 or 4 adverse events, often requiring dose modifications or interruptions, particularly within the first 4 weeks of treatment, indicating the need for careful monitoring during this period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent dose interruptions are required for patients receiving oral kinase inhibitor therapy for advanced renal cell carcinoma. La Vine, DB., Coleman, TA., Davis, CH., et al.[2022]

In a study of 90 patients with renal cell carcinoma, sequential treatment with sorafenib followed by sunitinib resulted in a median overall survival of 135 weeks, compared to 82 weeks for the reverse sequence, indicating that the order of administration may impact survival outcomes.

Both treatment sequences were well tolerated, with no increase in severe toxicity (grade 3-4), suggesting that sequential administration of these tyrosine kinase inhibitors is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential sorafenib and sunitinib for renal cell carcinoma. Sablin, MP., Negrier, S., Ravaud, A., et al.[2018]

Sunitinib is an effective first-line treatment for metastatic renal cell cancer (mRCC), showing superiority over interferon alpha in a phase III trial, but it comes with significant side effects like diarrhea, hypertension, and fatigue.

An alternative dosing schedule of sunitinib (2 weeks on, 1 week off) may offer similar efficacy with better tolerability, and ongoing trials are exploring its use alongside newer immune checkpoint inhibitors in mRCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib in the treatment of metastatic renal cell carcinoma. Schmid, TA., Gore, ME.[2020]

Sunitinib has been established as the standard first-line treatment for advanced renal cell carcinoma, based on results from a large-scale, long-term Phase III trial.

Conventional treatments like nephrectomy followed by IL-2 or IFN-alpha often do not provide long-term survival benefits, highlighting the importance of targeted therapies like sunitinib in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. Hutson, TE.[2018]

In a phase I study involving 26 patients with advanced renal cell carcinoma, the combination of sunitinib and bevacizumab showed an objective response rate of 52%, with one complete response and 12 partial responses observed.

However, the treatment was associated with significant safety concerns, including high rates of grade 3 to 4 hypertension and other toxicities, leading to 48% of patients discontinuing treatment; thus, further studies at the maximum-tolerated dose are not planned.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. Feldman, DR., Baum, MS., Ginsberg, MS., et al.[2022]

References

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

Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma. [2018]

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

Sunitinib for the treatment of metastatic renal cell carcinoma. [2022]

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

A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

[New therapeutic schedules of Sunitinib: Current evidence regarding the 2:1 scheme.] [2018]

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

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis. [2022]

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

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Medical treatment of metastatic renal cell carcinoma after the approval and market entry of multitargeted tyrosine kinase inhibitors in Germany]. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. [2022]

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

Frequent dose interruptions are required for patients receiving oral kinase inhibitor therapy for advanced renal cell carcinoma. [2022]

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

Sequential sorafenib and sunitinib for renal cell carcinoma. [2018]

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

Sunitinib in the treatment of metastatic renal cell carcinoma. [2020]

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

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. [2018]

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

Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. [2022]