Study to Evaluate the Safety and Efficacy of Bicalutamide in Combination With Sunitinib in Patients With TKIs-resistant RCC

A Phase I/II Study to Evaluate the Safety and Efficacy of Bicalutamide in Combination With Sunitinib in Patients With Receptor Tyrosine Kinase Inhibitor Resistant Renal Cell Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Bicalutamide in combination with Sunitinib

Detailed Description

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. After entering the study, patients will have sunitinib dosed at the 2 weeks ON and one week OFF scheduled. Dose and schedule modification of sunitinib will be allowed at the discretion of the treating physician. Bicalutamide will be administrated orally at 50 mg daily. This clinical study will utilize the Simon's optimal two stage design. Investigators will enroll 9 patients in the first stage. If no response is seen, then the trial is terminated for futility. Otherwise, accrual continues to a total of 16 patients. If at most 2 patients respond among the 16 patients, this therapy would warrant further investigation.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Roberto Pili, MD/PhD; Phone Number: (716) 878-3317; Email: rpili@buffalo.edu
• Study Contact Backup: Name: Kirsten Haden; Phone Number: 17168600267; Email: KHaden@gppconline.com

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • UB/ Great Lakes Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be willing and able to provide written informed consent for the trial.
2. Be greater than or equal to 18 years of age on day of signing informed consent.
3. Have measurable disease based on RECIST 1.1
4. Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
5. Demonstrate adequate organ function
6. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
7. Subjects of childbearing potential should be willing to use 2 methods of contraception for the course of the study through 120 days after the last dose of study medication
8. Male subjects without a previous vasectomy should agree to use an adequate method of contraception (i.e. abstinence, condom with spermicidal foam/gel/film/cream) starting with the first dose of study therapy through 120 days after the last dose of study therapy.
9. Subjects have archival tumor tissue available or are willing to undergo a baseline biopsy prior to treatment.
10. Subjects must have a life expectancy of at least 6 months.

Exclusion Criteria:

1. 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.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Has active Bacillus tuberculosis (TB)
4. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
5. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
6. Has an active infection requiring systemic therapy.
7. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
8. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
9. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
10. Has a known history of Human Immunodeficiency Virus (HIV)
11. Has known active Hepatitis B or Hepatitis C
12. Has received a live vaccine within 30 days of planned start of study therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bicalutamide in combination with Sunitinib; 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.	Drug: Bicalutamide in combination with Sunitinib; Antineoplastics, Antiandrogen; CYP3A4 Inhibitor; Other Names: CASODEX; (RS)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl sulfonyl]-2-hydroxy-2-methylpropanamide; UNII: A0Z3NAU9DP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess safety and tolerability of bicalutamide in combination with sunitinib in patients with RTKIs-resistant renal cell carcinoma.	Investigators will report the number of participants with treatment-related adverse events as assessed by CTCAE v4.0.	3 years
To assess efficacy of bicalutamide in combination with sunitinib in patients with RTKIs-resistant renal cell carcinoma.	Investigators will also report the number of patients who achieve either partial or complete response by RECIST criteria on tumor imaging.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize expression of AR-related micro-RNA (miR) in tumor and/or blood by polymerase chain reaction (PCR)	Outcome measure: ratio of miR expression with respect to the gene of reference	3 years
To characterize Kallikrein-2 (KLK2) expression in blood by ELISA	ELISA test calculates the concentration of protein as ng per ml of serum/blood.	3 years
To characterize androgen receptor (AR) expression in tumor samples immunohistochemistry (IHC)	The outcome measure is IHC score (scale goes from 0-3, 0 being better outcome and 3 being the worst outcome) (0): negative staining; : weak staining; : moderate staining; : strong staining	3 years
To characterize KLK2 expression in tumor samples immunohistochemistry (IHC)	The outcome measure is IHC score (scale goes from 0-3, 0 being better outcome and 3 being the worst outcome) (0): negative staining; : weak staining; : moderate staining; : strong staining	3 years

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Investigators: Principal Investigator: Roberto Pili, MD, State University of New York at Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: November 11, 2022
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 24, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Indoles; Pyrroles; Sunitinib; bicalutamide
• Other Study ID Numbers: STUDY00006224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No