Bortezomib for Prostate Cancer
(BORXPTEN Trial)
Recruiting in Palo Alto (17 mi)
Overseen byUmang Swami, MD, MS
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Utah
Must be taking: Androgen deprivation therapy
Disqualifiers: Neuropathy, Recent surgery, Brain metastases, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?The goal of this clinical trial is to test the anti-tumor activity of bortezomib in participants with Metastatic Castration Resistant Prostate Cancer (mCRPC) with PTEN Deletion.
The main question\[s\] it aims to answer is if the use of bortezomib will result in a decline in PSA for participants.
Participants will receive a sub-cutaneous injection of bortezomib for up 8 cycles. Each cycle is about 21 days.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it mentions a washout period (time without taking certain medications) for prohibited medications before starting the treatment. It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What data supports the effectiveness of the drug Bortezomib for prostate cancer?
Bortezomib, a drug known for treating multiple myeloma, has shown potential in prostate cancer by blocking certain pathways that help cancer cells survive, making them more likely to die. This suggests it might be effective against prostate cancer, although more research is needed to confirm this.
12345How does the drug Bortezomib differ from other prostate cancer treatments?
Bortezomib is unique because it is a proteasome inhibitor, which means it works by blocking the action of proteasomes (cellular complexes that break down proteins) to slow the growth of cancer cells. Unlike traditional hormone therapies for prostate cancer, Bortezomib can be combined with hormone blockade to potentially enhance treatment effectiveness without significant additional side effects.
678910Eligibility Criteria
Men over 18 with advanced prostate cancer resistant to hormone therapy and no prior mCRPC treatments can join. They must have a life expectancy over 3 months, treated or stable other cancers, good organ function, and agree to use contraception. Excluded are those with severe heart issues, active infections like TB or hepatitis B/C, recent major surgery or therapies, brain metastases, uncontrolled blood pressure or HIV.Inclusion Criteria
I can take care of myself but might not be able to do heavy physical work.
Absolute neutrophil count β₯ 1500/mm3
Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment in accordance with section 5.4.3
+17 more
Exclusion Criteria
You have experienced a strong allergic reaction in the past to the experimental drug or any of its ingredients.
Left ventricular ejection fraction < 50%
You are currently taking any experimental drugs for other research studies.
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a sub-cutaneous injection of bortezomib for up to 8 cycles, each cycle lasting 21 days
24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 years
Participant Groups
The trial tests bortezomib's effectiveness in reducing PSA levels in men with metastatic castration-resistant prostate cancer that has a specific genetic change (PTEN deletion). Participants will receive subcutaneous injections of bortezomib for up to eight cycles lasting about three weeks each.
1Treatment groups
Experimental Treatment
Group I: BortezomibExperimental Treatment1 Intervention
bortezomib starting at a dose of 1.3 mg per square meter of the body-surface area (BSA) subcutaneously on days 1, 4, 8, and 11 in a 21-day cycle.
Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:
πͺπΊ Approved in European Union as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
πΊπΈ Approved in United States as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
π¨π¦ Approved in Canada as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
π―π΅ Approved in Japan as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Huntsman Cancer Institute/University of UtahSalt Lake City, UT
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Who Is Running the Clinical Trial?
University of UtahLead Sponsor
References
Clinical update: proteasome inhibitors in hematologic malignancies. [2019]The proteasome inhibitor bortezomib (VELCADE; formerly PS-341, LDP-341, MLN341) is a novel dipeptide boronic acid. In cell culture and xenograft models, bortezomib showed potent activity, enhanced the sensitivity of cancer cells to traditional chemotherapeutics, and appeared to overcome drug resistance. In vitro, bortzomib downregulated the NF-kappaB pathway. NF-kappaB is a transcription factor that enhances the production of growth factors (e.g., IL-6), cell-adhesion molecules, and anti-apoptotic factors, all of which contribute to the growth of the tumor cell and/or protection from apoptosis. Phase II trials have been conducted in patients with relapsed and refractory multiple myeloma (SUMMIT trial, 202 patients) or relapsed myeloma (CREST trial, n=54) using a 1.3mg/m(2) dose given twice weekly for 2 weeks (days 1, 4, 8, 11; rest days 12-21). Both trials showed responses (including complete responses) with manageable toxicities, forming the basis for an ongoing phase III trial comparing response to bortezomib versus high-dose dexamethasone.
Bortezomib in multiple myeloma: a practice guideline. [2015]Bortezomib (Velcadeβ’, PS-341), a first-in-class proteasome inhibitor, has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma. We created a provincial guideline for the use of bortezomib, in newly diagnosed individuals (both eligible and ineligible for transplant) and in individuals with relapsed or refractory multiple myeloma.
Bortezomib: proteasome inhibition as an effective anticancer therapy. [2015]Inhibition of the proteasome results in disruption of protein homeostasis within the cell that can lead to apoptosis, a phenomenon preferentially observed in malignant cells. Bortezomib (VELCADE) is a first-in-class proteasome inhibitor developed specifically for use as an antineoplastic agent. Its first indication, for the treatment of relapsed myeloma in patients who have received at least two prior treatments and progressed on their previous treatment, was based in part on the magnitude of activity demonstrated in Phase II trials. An interim analysis of a Phase III trial demonstrated a significant efficacy advantage of bortezomib over high-dose dexamethasone in patients with relapsed myeloma. Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and early presentations of myeloma.
Proteasome inhibition blocks caspase-8 degradation and sensitizes prostate cancer cells to death receptor-mediated apoptosis. [2015]Proteasome inhibition through the administration of Velcade is a viable chemotherapeutic strategy that is approved to treat multiple myeloma and is being evaluated for efficacy against prostate cancer. Currently, the apoptotic pathways that contribute to this anticancer response are poorly understood. Our goal is to test the extent to which proteasome inhibition modulates apoptosis through death receptor pathways.
Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. [2020]Bortezomib (VELCADE) is a potent inhibitor of the 26S proteasome with broad antitumor activity. We performed a phase II study of bortezomib to evaluate its clinical effects in patients with metastatic breast cancer.
Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art. [2021]Bone health represents a major issue in castration-resistant prostate cancer (CRPC) patients with bone metastases; in fact, the frequently prolonged use of hormonal agents causes important modifications in physiological bone turnover and most of these men will develop skeletal-related events (SREs), including spinal cord compression, pathologic fractures and need for surgery or radiation to bone, which are estimated to occur in almost half of this patient population. In the last decade, several novel therapeutic options have entered into clinical practice of bone metastatic CRPC, with recent approval of enzalutamide and abiraterone acetate, cabazitaxel chemotherapy and radium-223, on the basis of survival benefit suggested by landmark Phase III trials assessing these agents in this setting. Conversely, although bone-targeted agents (BTAs)-such as the bisphosphonate zoledronic acid and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab-are approved for the prevention of SREs, these compounds have not shown benefit in terms of overall survival. However, emerging evidence has suggested that the combination of BTAs and abiraterone acetate, enzalutamide and the radiopharmaceutical radium-223 could result in improved clinical outcomes and prolonged survival in bone metastatic CRPC. In this review, we will provide an overview on bone tropism of prostate cancer and on the role of BTAs in metastatic hormone-sensitive and castration-resistant prostate cancer.
Two years of bicalutamide monotherapy in patients with biochemical relapse after radical prostatectomy. [2022]Salvage treatments for biochemical relapse (BCR) after radical prostatectomy (RP) have several problems in terms of indications or adverse events. We studied the possibility of 2 years of bicalutamide monotherapy for BCR after RP.
Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade. [2020]A single arm phase II trial of single-agent bortezomib (BZM) alone or combined with hormone blockade was conducted in patients with early PSA recurrence after definitive local therapy. The primary endpoint of this study was to determine the time to PSA relapse after BZM therapy alone or when BZM was combined with hormone blockade. The secondary endpoint was to determine the safety of combination therapy. Part A of the treatment schedule consisted of three cycles of BZM 1.3 mg/m2 IV given on days 1,4,8,11. If patients progressed on Part A, they were entered on Part B which consisted of a single dose of LH-RH antagonist, daily oral antiandrogen, and weekly BZM 1.3 mg/m2 for three out of four weeks for a total of three months. BZM treatment significantly decreased the slope of the log PSA (p=0.024) demonstrating that this agent alone was capable of slowing the rise of the PSA. Of eight patients treated with BZM alone five had stable disease, two progressed and 1 went off study secondary to toxicity. The major toxicity was neurotoxicity requiring discontinuation of therapy in three patients and treatment interruption in nine patients. Of those receiving Parts A and B or B only, there were 11 of 15 CRs with the average time to progression of 5.5 months. BZM treatment can change the slope of PSA rise and can be combined with hormone deprivation therapy without significant additional side effects; these agents are associated with a median time to CR of 42 days.
Prospects of immunotherapy for the treatment of prostate carcinoma--a review. [2019]The treatment of prostate carcinoma is dependent on the stage of the disease. Patients who present with clinically localized cancer or locally advanced tumors can be potentially cured by radical prostatectomy, radiation, and hormonal therapy. However, disease progression can occur in 30-50% of patients diagnosed with clinically localized cancer. The bone is the predominant site of metastases. Metastatic prostate cancer is first treated by androgen blockade but within a few months becomes hormone refractory. Hormone refractory metastatic prostate cancer is not responsive to conventional treatments, and patients have an expected survival of less than a year. It is essential to develop new approaches for the treatment of hormone refractory metastatic disease. Immunotherapy, based on enhancement of the host immune response against the tumor, has been used as an alternative therapy for the treatment of metastatic cancers refractory to conventional therapy in particular for melanoma and renal cell carcinoma. In this review, we will summarize various immunotherapeutic approaches developed over the last 18 years, and we will address the potential of immunotherapy for the treatment of metastatic prostate carcinoma by reviewing preclinical studies and initial clinical trials performed in this field.
Isotope Therapy for Castrate-Resistant Prostate Cancer: Unique Sequencing and Combinations. [2022]Radiopharmaceuticals used in the treatment of castrate-resistant prostate cancer are reviewed herein with an emphasis on sequential and combination therapies. Four bone-seeking radiopharmaceuticals had been approved in the United States. Three of these are Ξ²-emitters (phosphorus-32, strontium-89, samarium-153-ethylenediaminetetramethylene-phosphonic acid) that are approved for palliative purposes. One Ξ±-emitter (radium-223 [Ra]) is approved for prolongation of survival in bone metastatic castrate-resistant prostate cancer. Bone-seeking radiopharmaceuticals have been used in combination therapy with chemotherapy, hormones, and bisphosphonates for decades. Current combinations and clinical trials are primarily focused on Ra, given that overall survival benefit is associated with this radionuclide. Phase III trials with Ra were conducted in combination with a variety of standard hormonal therapies, bisphosphonates, and external beam radiation. Since the phase III Ra trials have been conducted, additional experience has been obtained with newer hormonal therapies such as abiraterone and enzalutamide, as well as with chemotherapies such as docetaxel. These therapies have been used both in combination with Ra and in sequence. Insights have arisen under each condition.A continuous evolution of radiopharmaceuticals is anticipated as these agents evolve in 2 distinct ways. First, current agents will evolve in combination with both current and emerging therapies, to create a better integrated and optimized approach. Second, radiopharmaceuticals that target the tumor (regardless of location) will continuously evolve. Therapies restricted to bone have inherent shortcomings, even in bone-tropic malignancies such as prostate cancer. Preliminary data with prostate-specific membrane antigen targeted Ξ²-emitters such as lutetium-177 are promising but need further evaluation. Prostate-specific membrane antigen targeted Ξ±-emitters are also in development. Given the molecular heterogeneity of tumor cells and the many shortcomings of molecularly targeted therapy, radiopharmaceuticals represent an attractive alternative approach given their capability of direct antitumor effects as well as their capability of microenvironmental disruption.