A Phase 1 interventional study of TVB-2640 and Enzalutamide in Prostatic Neoplasms, Castration-Resistant, sponsored by Weill Medical College of Cornell University. Recruiting at 1 site in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-21.
Sponsored by Weill Medical College of Cornell University · Phase 1, Interventional, and Treatment
The purpose of this study is to determine what effects (good and bad) Enzalutamide and TVB-2640 have in the treatment of prostate cancer whose prostate cancer has spread to other parts of their body and that has not gotten better with previous treatment. This study is a Phase I clinical trial. Phase I clinical trials test the side effects of an investigational drug or an investigational combination with another drug. "Investigational" means that the drug is still being studied and research doctors are trying to find out more about it. Although Enzalutamide is already being used to treat men with prostate cancer, combining Enzalutamide with TVB-2640 together in patients with prostate cancer is considered experimental. This research study is being done because additional effective treatments are needed for prostate cancer that has spread and is growing despite hormone suppression. By doing this study, the investigators hope to learn if combining Enzalutamide with TVB-2640 can be done safely. Participation in this research will last about 12 to 24 months after enrollment.
This phase I, open-label, dose-escalation study is designed to evaluate the dose limiting toxicities (DLTs) and maximum-tolerated dose (MTD) of TVB-2640 plus Enzalutamide and establish the TVB-2640 dose recommended for further investigation in phase 2 (i.e., recommended phase 2 dose [RP2D]). Patients with a confirmed histological or cytological diagnosis of prostate cancer (PC), evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan), serum testosterone \<50 ng/dl, who had progressed on androgen-depletion therapy (ADT), with documented progressive metastatic castration-resistant prostate cancer (mCRPC) based on Prostate Cancer Working Group 3 (PCWG3) criteria and no previously treatment with cytotoxic chemotherapy are eligible. This study represents the first clinical evaluation of TVB-2640 in combination with Enzalutamide. All patients will receive Enzalutamide monotherapy at the approved dose of 160 mg once daily for 28 days to reach the steady state as determined by measuring Enzalutamide and des-methyl-Enzalutamide levels. Participants who complete the Enzalutamide run-in period will begin oral TVB-2640 at the dose of 100 mg. The dose escalation scheme will be the Bayesian optimal interval (BOIN) design with additional dose levels of 100 mg, 150mg, 200 mg, 250 mg, and 300mg daily. The maximum sample size for the phase I will be 30 patients and the target DLT rate is 25% or less and a maximum of 9 patients at any dose level.
84 studies on the registry are indexed under Prostatic Neoplasms, Castration-Resistant; 30 are open to participants now.
This study's planned enrollment of 30 is below the median of 82 across 61 interventional studies indexed under Prostatic Neoplasms, Castration-Resistant.
Browse Prostatic Neoplasms, Castration-Resistant studies →Weill Medical College of Cornell University is the lead sponsor of 867 studies on the registry; 160 are open to participants now.
Of its 119 completed or terminated interventional studies of FDA-regulated products, 91 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participant has uncontrolled, significant intercurrent or recent Cardiovascular disorders including, but not limited to, the following conditions:
i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
ii. Uncontrolled hypertension defined as sustained blood pressure (BP) >140 mm Hg systolic or >90 mm Hg diastolic despite optimal antihypertensive treatment.
iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
Drug: TVB-2640 · Drug: Enzalutamide
TVB- 2640 at 100 mg, 150mg, 200 mg, 250 mg, or 300mg daily, orally; dose determined by BOIN dose escalation per the protocol
160 mg daily PO
Also known as: Xtandi
Optimal dose of TVB-2640 in combination with Enzalutamide, as determined by the maximum tolerated dose (MTD)
The maximum tolerated dose (MTD) is defined as the highest dose level at which ≤1 patient experiences a dose-limiting toxicity, as defined in the protocol (DLT). Once all the patients are accrued, the MTD will be determined by performing isotonic regression on the pooled data.
Time frame: Day 28
Number of adverse events (evaluated using the NCI CTCAE v5.0) of different doses of TVB-2640 in combination with Enzalutamide
All observed AEs will be tabulated and reported as relative frequencies (i.e., fraction of patients with that AE). This will be done by AE and maximum grade experienced within a patient. The fraction of patients with each AE by grade will be estimated with a binomial point estimate and corresponding 95% binomial confidence interval (CI). AEs will be collected until 30 days following the last dose of study drug. AEs will be reported for each different dose of TVB-2640 given.
Time frame: 12 months
Mean TVB-2640 total exposure (as measured by the area under the drug serum concentration vs. the time from administration curve [AUC])
Peripheral blood will be drawn at: Day 28: * Pre- enza dose * Post-dose * 1 hours (±5 min) * 2 hours (±5 min) * 4 hours (±30 min) Days 36-37: * Pre-TVB-2640 dose * Post-dose * 2 hours (±5 min) * 4 hours (±30 min) * 6 hours (±30 min) * 8 hours (±30 min) * 24-hours (±1 hour) Days 43-44: * Pre-TVB-2640 dose * Post-dose * 30 minutes (±5 min) * 1 hour (±5 min) * 2 hours (±5 min) * 4 hours (±30 min) * 6 hours (±30 min) * 8 hours (±30 min) * 24-hours (±1 hour) Days 50-51: * Pre-TVB-2640 dose * Post-dose * 30 minutes (±5 min) * 1 hour (±5 min) * 2 hours (±5 min) * 4 hours (±30 min) * 6 hours (±30 min) * 8 hours (±30 min) * 24-hours (±1 hour)
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean Enzalutamide total exposure (as measured by the area under the drug serum concentration vs. the time from administration curve [AUC])
Peripheral blood will be drawn at: Day 28: * Pre- enza dose * Post-dose * 1 hours (±5 min) * 2 hours (±5 min) * 4 hours (±30 min) Days 36-37: * Pre-TVB-2640 dose * Post-dose * 2 hours (±5 min) * 4 hours (±30 min) * 6 hours (±30 min) * 8 hours (±30 min) * 24-hours (±1 hour) Days 43-44: * Pre-TVB-2640 dose * Post-dose * 30 minutes (±5 min) * 1 hour (±5 min) * 2 hours (±5 min) * 4 hours (±30 min) * 6 hours (±30 min) * 8 hours (±30 min) * 24-hours (±1 hour) Days 50-51: * Pre-TVB-2640 dose * Post-dose * 30 minutes (±5 min) * 1 hour (±5 min) * 2 hours (±5 min) * 4 hours (±30 min) * 6 hours (±30 min) * 8 hours (±30 min) * 24-hours (±1 hour)
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean maximum serum concentration (Cmax) of TVB-2640
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean maximum serum concentration (Cmax) of Enzalutamide
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean minimum serum concentration (Cmin) of TVB-2640
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean minimum serum concentration (Cmin) of Enzalutamide
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean TVB-2640 volume of distribution at steady state
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean Enzalutamide volume of distribution at steady state
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean time to maximum TVB-2640 serum concentration (Tmax) after administration
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean time to maximum Enzalutamide serum concentration (Tmax) after administration
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean Serum half-life (T1/2) of TVB-2640
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean Serum half-life (T1/2) of Enzalutamide
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean TVB-2640 clearance
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Mean Enzalutamide clearance
Peripheral blood will be drawn at the following times: Day 28: * Pre- enza dose * 1 hours (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose Days 36-37: * Before TVB-2640 administration * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 43-44: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose Days 50-51: * Before TVB-2640 administration * 30 minutes (±5 min) post-dose * 1 hour (±5 min) post-dose * 2 hours (±5 min) post-dose * 4 hours (±30 min) post-dose * 6 hours (±30 min) post-dose * 8 hours (±30 min) post-dose * 24-hours (±1 hour) post-dose
Time frame: Day 28; Days 36-37; Days 43-44; Days 50-51
Prostate-Specific Antigen (PSA) Response Rate
The PSA response rate will be evaluated using PCWG3 criteria and defined as the proportion of patients with a PSA decline of at least 50%. Any change from baseline is confirmed by a second measurement at least 3 weeks later. PSA Response Rate will be evaluated using PCWG3 criteria and defined as following: Percentage change from baseline in PSA to 12 weeks post Enzalutamide plus TVB-2640. Only evaluate for patients with at least 12 weeks of treatment, the PSA assessment at 12 weeks (84 days +/-3 days) will be used; Maximum percent decrease in PSA from baseline that occurs at any point after treatment.
Time frame: Baseline; 12 weeks
Overall radiographic response rate
Tumor response will be evaluated using the PCWG3 criteria. Patients with measurable disease will be evaluated for clinical benefit as determined by tumor response using RECIST v1.1. Patients with non-measurable bone disease will be evaluated for progression based on the presence of any new lesions by bone scans. Radiographic tumor evaluation will be performed at screening and every 3 cycles or more frequently as determined by the investigator. Using the tumor response that is determined by the investigator, best overall response will be determined using RECIST v1.1. Best overall response is defined as the best response recorded from the start of treatment until disease progression or study exit. The overall response rate will be determined as the number of patients with a confirmed PR or CR divided by the total number of patients evaluable for overall response.
Time frame: From baseline until disease progression for a maximum of 2 years from enrollment
Overall median progression free survival (PFS)
Overall progression free survival (PFS) is determined using the PCWG3 criteria. Overall PFS is measured from screening until the time that disease progression (radiographic progressive disease or clinical deterioration) or death is documented, whichever occurs first.
Time frame: From baseline until disease progression or death from any cause for a maximum of 2 years from enrollment
Median radiographic progression free survival (PFS) as assessed by PCWG3
Radiographic progression-free survival (rPFS) is determined using the PCWG3 criteria to assess both soft-tissue and bone assessments. The rPFS is measured from screening until the time the first radiographic scan shows disease progression, or until the time of death, whichever occurs first. Patients who do not progress radiographically or did not die prior to study exit are censored on the date of their last dose of Enzalutamide plus TVB-2640. PFS will be summarized with a Kaplan-Meier curve. The Kaplan-Meier estimator will be used to determine the 6-month and 12-month PFS rates. Each estimate will have a corresponding 95% confidence interval. The median PFS will also be estimated with a corresponding 95% confidence interval
Time frame: From baseline until disease progression for a maximum of 2 years from enrollment
Plan to share: No
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Prostatic Neoplasms, Castration-Resistant→
Weill Medical College of Cornell University