ctDNA-Guided Therapy for Prostate Cancer
(PROTRACT Trial)
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: British Columbia Cancer Agency
Must be taking: LHRH agonist/antagonist
Must not be taking: Anti-androgens, Chemotherapy
Disqualifiers: Severe illness, Active malignancy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests if using a blood marker to choose between two treatments is better than doctors choosing the treatment for advanced prostate cancer patients who did not respond to previous therapy.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you must maintain LHRH agonist/antagonist therapy if not surgically castrated. It's best to discuss your current medications with the trial team.
What data supports the idea that ctDNA-Guided Therapy for Prostate Cancer is an effective drug?
The available research shows that docetaxel, a drug used in ctDNA-Guided Therapy for Prostate Cancer, has been effective in extending the survival of patients with advanced prostate cancer. Studies like SWOG 99-16 and TAX 327 demonstrated a survival benefit for patients using docetaxel-based therapy. Additionally, docetaxel has been shown to reduce prostate-specific antigen (PSA) levels, which is a marker of prostate cancer activity, by 50% or more in some patients. Compared to other treatments like mitoxantrone and prednisone, docetaxel-based therapy has shown a 20% to 24% survival benefit, leading to its approval by the US Food and Drug Administration for treating metastatic hormone-refractory prostate cancer.
12345What safety data is available for ctDNA-guided therapy in prostate cancer?
The safety data for ctDNA-guided therapy in prostate cancer can be inferred from studies on docetaxel and enzalutamide, which are components of this treatment. Docetaxel, evaluated in various studies, has shown a survival advantage and is well tolerated, with Phase III trials demonstrating its efficacy over mitoxantrone and prednisolone. Enzalutamide, approved by the FDA for castration-resistant prostate cancer (CRPC), has been shown to be well tolerated in a Phase III trial, with a significant improvement in overall survival. A Phase Ib study combining docetaxel and enzalutamide also assessed safety and tolerability, indicating that these treatments have been evaluated for safety in clinical settings.
678910Is the drug Docetaxel, Enzalutamide a promising treatment for prostate cancer?
Yes, Docetaxel, Enzalutamide is a promising treatment for prostate cancer. Research shows that Docetaxel can improve survival in patients with advanced prostate cancer. It is part of a group of therapies that offer more than just temporary relief, potentially extending the lives of patients. Additionally, using circulating tumor cells and DNA can help predict how well a patient might respond to this treatment, making it a valuable option in managing prostate cancer.
511121314Eligibility Criteria
This trial is for adult males over 18 with metastatic castration-resistant prostate cancer who have previously been treated with abiraterone. Participants must show disease progression, consent to tissue analysis, and have adequate organ function. They cannot join if they've had seizures, brain metastases, certain gastrointestinal disorders, prior enzalutamide or docetaxel chemotherapy (with exceptions), other active cancers (with exceptions), or uncontrolled hypertension.Inclusion Criteria
My bone scans show at least 2 new lesions, confirmed 8 weeks apart.
I am eligible for treatment with enzalutamide or docetaxel.
My prostate cancer has worsened despite treatment with abiraterone.
+17 more
Exclusion Criteria
My blood pressure is not higher than 160/100 mmHg.
I have had chemotherapy with docetaxel or cabazitaxel, except if it was for early-stage disease and I didn't worsen for 12 months after.
I have a digestive condition that affects how my body absorbs nutrients.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either biomarker-directed therapy or clinician's choice of enzalutamide or docetaxel until disease progression, with a cross-over to the other therapy upon progression
Until disease progression
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 year
Extension
Participants may continue to be monitored for overall survival and other outcomes
2 years
Participant Groups
The study aims to optimize prostate cancer treatment by using circulating tumor DNA (ctDNA) levels to decide between two drugs: Enzalutamide for ctDNA fraction <2% and Docetaxel for ≥2%. This approach is compared against the clinician's choice of either drug without ctDNA guidance.
2Treatment groups
Experimental Treatment
Active Control
Group I: A: Biomarker directed Therapy (BT)Experimental Treatment2 Interventions
ctDNA fraction \<2% receives enzalutamide, and ctDNA fraction ≥2% receives docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).
Group II: B: Clinician's Choice (CC)Active Control2 Interventions
Enzalutamide or docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).
Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇪🇺 Approved in European Union as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇨🇦 Approved in Canada as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇯🇵 Approved in Japan as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
BC Cancer - Centre for the NorthPrince George, Canada
Sunnybrook Health Sciences CentreToronto, Canada
London Health Sciences CentreLondon, Canada
BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)Kelowna, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
British Columbia Cancer AgencyLead Sponsor
References
Docetaxel in the integrated management of prostate cancer. Current applications and future promise. [2018]Docetaxel (Taxotere)-based regimens can be included among the most effective treatment options for the management of patients with advanced, androgen-independent prostate cancer. Results with docetaxel as a single agent and in combination regimens with estramustine (Emcyt) have consistently achieved a palliative response, reduced serum PSA levels by > or = 50%, and produced objective responses in patients with measurable disease. In addition, encouraging survival data have been demonstrated in several phase II trials. The ability to administer docetaxel on a weekly basis has substantially enhanced research efforts for treatment in prostate cancer patients. The results of ongoing phase III randomized trials evaluating docetaxel regimens in androgen-independent prostate cancer are eagerly awaited for their potential to definitively demonstrate a beneficial impact on overall patient survival. Docetaxel-containing regimens are likely to demonstrate a substantial role in the management of early-stage prostate cancer patients in the adjuvant and neoadjuvant settings, where clinical investigations are under way. In addition, study results from ongoing trials that integrate docetaxel with hormonal therapies for patients with biochemical recurrence following definitive local treatments will be important in refining the future role of chemotherapy for prostate cancer in general. The preliminary findings from studies conducted with docetaxel are encouraging and await final analysis. Finally, preliminary results from studies exploring combination regimens of docetaxel and novel agents that possess completely different mechanisms of action (eg, proapoptotic agents, angiogenesis inhibitors, and vitamin D analogs) have demonstrated the regimens to be feasible and safe, with promising early response data. These types of investigational studies will likely occupy a dominant position in future research initiatives for patients with advanced prostate cancer.
New paradigms for advanced prostate cancer. [2022]In men with metastatic hormone-refractory prostate cancer, androgen blockade produces dramatic and rapid declines in prostate-specific antigen (PSA), bone pain, and urinary tract obstruction. Nevertheless, there have been limited options with at best palliative results for patients who progress despite a castrate testosterone level. This paradigm changed in 2004 with the publication of 2 randomized clinical trials that demonstrated a 20% to 24% survival benefit for docetaxel-based therapy when compared to mitoxantrone and prednisone, data that supported US Food and Drug Administration approval of docetaxel-based therapy for the treatment of metastatic hormone-refractory prostate cancer. This article reviews the preliminary data and the timing and sequencing implications of ongoing clinical trials. Studies are evaluating the combination of docetaxel with agents that target bone, tumor vasculature, and the vitamin D receptor as well as second-line agents, such as satraplatin. The role of immune therapy is also evolving, and further studies will define the optimal timing of chemotherapy with immune therapy.
Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. [2018]Hormone-refractory prostate cancer is the terminal step in the natural history of prostate cancer. To date, no chemotherapeutic agents have been shown to impact clinical outcome at this stage. Recently, the Food and Drug Administration approved the combination of mitoxantrone and prednisone based solely on its superior palliative effects as compared to steroids alone in 2 randomized trials. Progress in biologically driven drug development has led to the identification of several estramustine-based regimens that, although based on single institution experience, appear to have at least a comparable but very promising level of activity in hormone-refractory prostate cancer patients. One such combination, estramustine plus docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA), is particularly attractive because of its convenient schedule and side effect profile. To objectively assess the therapeutic benefit of this combination, the Southwest Oncology Group is initiating a randomized phase III trial comparing estramustine and docetaxel with the standard arm of mitoxantrone and prednisone using time to progression and survival as the primary end points. Secondary end points will include toxicity profiles, assessments of quality of life parameters, and magnitude of decline of prostate-specific antigen levels between the two treatment arms.
High-risk localized prostate cancer: integrating chemotherapy. [2018]Docetaxel (Taxotere); Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com) is the first agent to significantly extend survival in hormone-refractory prostate cancer. Because agents active in advanced cancers tend to be beneficial in earlier stage disease, docetaxel is now to be assessed, along with hormonal therapy, in the adjuvant setting among patients whose localized prostate cancer has features that put them at particular risk for recurrence and cancer-specific mortality. Data from a pilot study suggest that neo-adjuvant treatment with docetaxel may be appropriate for selected high-risk patients and that such treatment can be undertaken without increasing surgical morbidity. Gene-expression profiling of tissue before and after docetaxel treatment is providing further insight into its effects. A randomized trial, conducted by the Cancer and Leukemia Group B, will evaluate neoadjuvant docetaxel in high-risk patients, whereby patients will be randomized to either immediate radical prostatectomy or surgery preceded by hormonal therapy plus docetaxel. Another large randomized trial will be evaluating the effect of adjuvant hormonal therapy with or without docetaxel in high-risk men after radical prostatectomy.
The current role of chemotherapy in metastatic hormone-refractory prostate cancer. [2022]Since the publication of the Southwest Oncology Group (SWOG) 99-16 and TAX 327 studies, which demonstrated a survival benefit for docetaxel-based therapy, clinicians for the first time have a therapy to offer men with metastatic prostate cancer that is not merely palliative in its effects. Phase 2 and phase 3 trials are now building on the findings of SWOG 99-16 and TAX 327 by evaluating the potential of combination taxane-based therapies, such as docetaxel plus high-dose calcitriol, docetaxel-estramustine-bevacizumab, and docetaxel-thalidomide. The optimal timing of docetaxel-based chemotherapy is still unknown, as there are no prospective clinical trial data to indicate whether earlier treatment (eg, at the time of prostate-specific antigen failure) is more or less effective than later treatment (eg, in metastatic and/or symptomatic disease).
A phase II study of higher dose docetaxel in androgen-independent prostate cancer. [2018]To assess the efficacy and toxicity profile of single agent docetaxel at a higher dose than previously evaluated in patients with androgen-independent prostate cancer (AIPC).
Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. [2021]Prostate cancer is the most common malignancy among men found to be the second leading cause of male cancer-related mortality due to development of resistance against androgen deprivation therapy (ADT). With the advancement in understanding of prostate cancer, numbers of agents have been emerged to target Androgen-Receptor (AR) signaling for the treatment of castration resistant prostate cancer (CRPC). Food and Drug Administration (FDA) has recently approved enzalutamide (XTANDI) for the treatment of CRPC. Androgen receptor promotes the prostate cancer progression after transformation. Androgen receptor signaling leads to CRPC when cellular nucleus binds to DNA and increases pro cancer gene expression. In phase ΙΙΙ clinical trial, enzalutamide showed that 160 mg once daily oral administration is well tolerated and significantly enhanced overall survival in men with CRPC after chemotherapy, demonstrated by reduction in the serum prostate specific antigen (PSA) level and increased survival rate by 4.8 months.
Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer. [2021]Preclinical evidence suggests that both docetaxel and enzalutamide target androgen receptor translocation and signaling. This phase Ib study assessed the safety, tolerability, and pharmacokinetics of docetaxel when administered with enzalutamide as first-line systemic chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC).
Docetaxel for the treatment of prostate cancer. [2018]Prostate cancer accounts for 12% of male cancer deaths, amounting to almost 10,000 deaths per year in the UK. Patients that develop metastatic disease may have their prostate cancer controlled for approximately 2 years with androgen deprivation but invariably progress to a castrate-independent state and succumb to metastatic disease. The previous experience of cytotoxic chemotherapy in hormone-refractory prostate cancer has yielded modest improvements in quality of life, with mitoxantrone in widest use. However, following encouraging Phase II data, two Phase III trials have demonstrated a survival advantage associated with the use of the synthetic taxoid cytotoxic docetaxel (Taxotere) over mitoxantrone and prednisolone. Moreover, this treatment was well tolerated. Therefore, docetaxel is set to be the standard by which future interventions are judged and a platform for future trials containing novel molecular therapies.
Docetaxel plus prednisone versus mitoxantrone plus prednisone for metastatic hormone-refractory prostate cancer in Chinese patients: experience of a single center. [2018]To preliminarily investigate the efficacy of docetaxel plus prednisone and mitoxantrone plus prednisone for treating metastatic hormone-refractory prostate cancer and to further evaluate its adverse events in Chinese patients.
Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer. [2019]Several systemic therapeutic options exist for metastatic castrate-sensitive prostate cancer (mCSPC). Circulating tumor DNA (ctDNA) can molecularly profile metastatic castration-resistant prostate cancer and can influence decision-making, but remains untested in mCSPC.
Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. [2022]Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan.
The potential of using circulating tumour cells and their gene expression to predict docetaxel response in metastatic prostate cancer. [2023]Docetaxel improves overall survival (OS) in castration-resistant prostate cancer (PCa) (CRPC) and metastatic hormone-sensitive PCa (mHSPC). However, not all patients respond due to inherent and/or acquired resistance. There remains an unmet clinical need for a robust predictive test to stratify patients for treatment. Liquid biopsy of circulating tumour cell (CTCs) is minimally invasive, can provide real-time information of the heterogeneous tumour and therefore may be a potentially ideal docetaxel response prediction biomarker.
AR gene rearrangement analysis in liquid biopsies reveals heterogeneity in lethal prostate cancer. [2022]Castration-resistant prostate cancer (CRPC) is driven by AR gene aberrations that arise during androgen receptor (AR)-targeted therapy. AR amplification and mutations have been profiled in circulating tumor cells (CTCs), but whether AR gene rearrangements can be assessed in CTCs is unknown. In this study, we leveraged CRPC cell lines with defined AR gene rearrangements to develop and validate a CTC DNA analysis approach that utilized whole genome amplification and targeted DNA-sequencing of AR and other genes important in CRPC. We tested the utility of this approach by analyzing matched CTC DNA and plasma cell-free DNA (cfDNA) from a case series of ten CRPC patients. One of ten CTC samples and two of ten cfDNA samples were positive for AR gene rearrangements. All AR gene rearrangements were discordant between matched liquid biopsy samples. One patient harbored separate AR gene rearrangements in CTC DNA and cfDNA, but concordant AR amplification and AR T878A mutation. This patient also displayed concordant loss of TP53 and PTEN, but the loss of RB1 in cfDNA only. The overall frequency of discordant alterations in these genes between matched CTC DNA and cfDNA was high. This study establishes the technical feasibility of analyzing structural rearrangements, mutations, and copy number variants in AR and other CRPC genes using two different sources of DNA from a single blood sample. Paired CTC DNA and cfDNA analysis may have utility for capturing the heterogeneity of genetic alterations in CRPC patients.