scholarly journals 954 Clinical results from a phase I dose escalation study in treatment-naïve early stage prostate cancer patients with ORCA-010, a potency enhanced oncolytic replication competent adenovirus

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A1004-A1004
Author(s):  
Tereza Brachtlova ◽  
Allan Abramovitch ◽  
Jonathan Giddens ◽  
Peter Incze ◽  
Kenneth Jansz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Adverse Events ◽  
Phase I ◽  
Cancer Patients ◽  
Dose Escalation ◽  
Safety Profile ◽  
Host Immune System ◽  
Intratumoral Administration ◽  
Treatment Naïve

BackgroundOncolytic adenoviruses have proven to be clinically promising immunotherapeutic agents for the treatment of cancer. Besides the direct anti-tumor activity of oncolytic adenoviruses, their ability to create a favorable microenvironment for the action of the host immune system against unique cancer cell determinants and a non-compromised host immune system are recognized as a key factors in successful oncolytic cancer treatment.Considering the role of the host immune system, treatment-naive patients with early stage localized prostate cancer were enrolled in a phase I trial with ORCA-010. Here we report on the safety of intratumoral administration of ORCA-010 and present an interim analysis of the clinical and immunological responses observed.MethodsTreatment-naïve prostate cancer patients with localized disease (stage I or II) were treated with a single intratumoral administration of ORCA-010 in a phase I dose escalation study. Nine patients in three dose escalation cohorts (1E11, 1E12 or 1.5E12 viral particles/administration) were treated based on a 3+3 design with a 1-year follow-up period.The primary study objectives include the safety profile of intratumoral administration of ORCA-010. Secondary objectives include 1) evaluation of the biological activity and antitumor efficacy of intratumoral administration of ORCA-010; 2) to evaluate potential antitumor immune responses and 3) to assess shedding of ORCA-010.ResultsNine patients with localized prostate cancer have been treated with a single intratumoral administration of ORCA-010. The safety profile demonstrated excellent tolerability and safety of ORCA-010 treatment with no DLTs reported. Treatment related adverse events observed in all patients were limited to transient grade I and grade II adverse events.Shedding analyses demonstrated active replication of ORCA-010 post administration and a viremia peak was observed in all patients within 1 week post administration. Coinciding with the viral load, free PSA increased significantly post treatment and returned to under 10 ng/mL 1-2 months post administration. Preliminary analyses of the MRI data of the low dose cohorts demonstrated a significant reduction of prostate size 6 months post treatment in patients with significantly enlarged prostates prior to treatment.ConclusionsIntratumoral administration of ORCA-010 in treatment-naïve prostate cancer patients demonstrated an excellent safety profile, with no DLTs observed and transient grade I and II adverse events. Preliminary analyses of the data demonstrate viral replication post administration, encouraging initial anti-tumor activity and a prostate size reduction in prostate cancer patients with enlarged prostates.Trial RegistrationNCT04097002Ethics ApprovalThe study was approved by Advarra institutional review board IRB#00000971 and patients completed an ICF prior to enrollment into the study.

A phase I, dose-expansion cohort study on the safety of a cannabidiol for biochemical recurrence in prostate cancer patients.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS263-TPS263
Author(s):  
Zin Myint ◽  
William H. St Clair ◽  
Stephen Strup ◽  
Peng Wang ◽  
Andrew Callaway James ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Acute Toxicity ◽  
Phase I ◽  
Cancer Patients ◽  
Prostate Specific Antigen ◽  
Dose Escalation ◽  
Specific Antigen ◽  
Dependent Manner ◽  
Expansion Cohort

TPS263 Background: Cannabinoids, widely used in pain control, as an appetite stimulant, and anti-emetic in cancer patients, may play role as an anti-carcinogenic agent. A preclinical study demonstrated that cannabinoid receptors (CB1 and CB2) were highly expressed in human androgen-responsive prostate cancer (PCa) cells (LNCaP) as compared to normal prostate epithelial cells (PrEC). When these two cell lines were treated with a potent cannabinoid receptor agonist, PCa cells showed a decrease in prostate-specific antigen (PSA) protein expression and increased apoptosis in a dose and time-dependent manner with no effect seen in PrEC cells. An FDA-approved cannabidiol (CBD) agent, is derived from Cannabis sativa L. plants. Extracts from these plants are processed to yield pure CBD and contain less than 0.5% THC. We will expand these preclinical studies with a phase I trial. Methods: This trial is an open-label, single-center, phase I dose escalation study followed by dose expansion to evaluate acute toxicity, long-term safety and tolerability, and preliminary antitumor activity of cannabidiols in patients with biochemically recurrent (BCR) PC after primary definitive local therapy and prostate-specific antigen doubling time ≤ 12 months. The dose escalation will be determined by a Bayesian Optimal Interval design and the target dose-limiting toxicity rate is set at 30%. An additional 6-9 patients will be enrolled as an expansion cohort once the maximum tolerated dose is determined. Patients will be treated for a total 90 days with a 10 day taper. The primary objective is to evaluate the acute toxicity and long-term safety and tolerability of cannabidiols in patients with BCR. The secondary objective includes measuring changes in serial PSA levels, PSA velocity, and testosterone levels and to assess health-related quality of life (EORTC QLQ-C30 and QLQ-PR 25) from baseline throughout the treatment period. CB receptor 1 and 2 expression levels by immunohistochemistry staining will be evaluated from archival prostatectomy specimens if available as an exploratory objective. This trial opened on 7.28.2020 and has started enrollment. Clinical trial information: NCT04428203.

Cross-trial Analysis of Immunologic and Clinical Data Resulting From Phase I and II Trials of MVA-5T4 (TroVax) in Colorectal, Renal, and Prostate Cancer Patients

2010 ◽  
Vol 33 (9) ◽  
pp. 999-1005 ◽  
Author(s):  
Richard Harrop ◽  
William Shingler ◽  
Michelle Kelleher ◽  
Jackie de Belin ◽  
Peter Treasure
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Clinical Data ◽  
Trial Analysis ◽  
Phase I And Ii

scholarly journals EP-1577: Prostate cancer SBRT dose escalation to the dominant nodule/s: Phase I and immunological effects

2018 ◽  
Vol 127 ◽  
pp. S849
Author(s):  
F. Herrera ◽  
V. Valerio ◽  
A. Harari ◽  
B. Berthold ◽  
J.Y. Meuwly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
S Phase ◽  
Immunological Effects

scholarly journals Marizomib alone or in combination with bevacizumab in patients with recurrent glioblastoma: phase I/II clinical trial data

2021 ◽  
Author(s):  
Daniela A Bota ◽  
Warren Mason ◽  
Santosh Kesari ◽  
Rajiv Magge ◽  
Benjamin Winograd ◽  
...  
Keyword(s):  
Phase I ◽  
Blood Brain Barrier ◽  
Dose Escalation ◽  
Safety Profile ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Brain Barrier ◽  
Part C ◽  
Blood Brain

Abstract Background This phase I/II trial in patients with recurrent glioblastoma (GBM) evaluates the safety and preliminary efficacy of marizomib, an irreversible pan-proteasome inhibitor that crosses the blood–brain barrier. Patients and Methods Part A assessed the safety and efficacy of marizomib monotherapy. In Part B, escalating doses of marizomib (0.5–0.8 mg/m2) in combination with bevacizumab were evaluated. Part C explored intra-patient dose escalation of marizomib (0.8–1.0 mg/m2) for the combination. Results In Part A, 30 patients received marizomib monotherapy. The most common AEs were fatigue (66.7%), headache (46.7%), hallucination (43.3%), and insomnia (43.3%). One patient (3.3%) achieved a partial response. In Part B, the recommended phase II dose of marizomib was 0.8 mg/m2 when combined with bevacizumab 10 mg/kg. In Part C, dose escalation to 1.0 mg/m2 was not tolerated. Pooled analysis of 67 patients treated with marizomib ≤0.8 mg/m2 and bevacizumab showed a non-overlapping safety profile consistent with the known safety profile of each agent: the most common grade ≥3 AEs were hypertension (16.4%), confusion (13.4%), headache (10.4%), and fatigue (10.4%). The overall response rate was 34.3%, including 2 patients with complete response. Six-month progression-free survival was 29.8%; median overall survival was 9.1 months. Conclusions The safety profile of marizomib as monotherapy and in combination with bevacizumab was consistent with previous observations that marizomib crosses the blood–brain barrier. Preliminary efficacy did not demonstrate a meaningful benefit of the addition of marizomib to bevacizumab for the treatment of recurrent GBM.

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