scholarly journals Feasibility, safety, and acceptability of a remotely monitored exercise pilot CHAMP: A Clinical trial of High‐intensity Aerobic and resistance exercise for Metastatic castrate‐resistant Prostate cancer

2021 ◽  
Author(s):  
Stacey A. Kenfield ◽  
Erin L. Van Blarigan ◽  
Neil Panchal ◽  
Alexander Bang ◽  
Li Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Resistance Exercise ◽  
High Intensity ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Overall survival after 177Lu-PSMA-617 molecular radiotherapy in patients with metastatic castrate-resistant prostate cancer: Post-hoc analysis of a prospective phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5549-5549 ◽  
Author(s):  
Jeremie Calais ◽  
Jeannine Gartmann ◽  
Wesley R Armstrong ◽  
Pan Thin ◽  
Kathleen Nguyen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Post Hoc Analysis ◽  
Molecular Radiotherapy ◽  
Prospective Phase ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Post Hoc

5549 Background: This was an open-label randomized prospective bi-centric single-arm phase II clinical trial of 177Lu-PSMA-617 molecular radiotherapy in patients with progressive metastatic castrate-resistant prostate cancer (mCRPC) conducted at University of California Los Angeles (USA) and Excel Diagnostics & Nuclear Oncology Center (Houston, TX, USA) (NCT03042312). The study was investigator-initiated under an investigational new drug approval protocol (IND#133661) with authorization of charging for investigational drug (cost-recovery, Title 21 CFR 312.8). We report here the post-hoc analysis of overall survival (OS) in a single-study site cohort (UCLA). Methods: Patients with progressive mCRPC (biochemical, radiographic, or clinical) after ≥1 novel androgen axis drug (NAAD), either chemotherapy (CTX) naïve or post-CTX, with sufficient bone marrow reserve, normal kidney function, and sufficient PSMA-target expression by PET were eligible. Patients received up to 4 cycles of 177Lu-PSMA-617 every 8±1 weeks and were randomized into 2 treatment activities groups (6.0 or 7.4 GBq). Efficacy was defined as serum PSA decline of ≥50% from baseline and served as primary endpoint (hypothesis: ≥40% of responders after 2 cycles). Results: 43 patients were randomized to the 6.0 GBq (n= 14) and 7.4 GBq (n=29) treatment arms. 11/43 (26%) were CTX naïve while 10/43 (23%), 12/43 (28%), 5/43 (12%) and 5/43 (12%) had received 1, 2, 3 or 4 CTX regimens. Median baseline PSA was 29.2 ng/ml (mean 228.8, range 0.5-2082.6). 21/43 (49%) completed 4 cycles of 177Lu-PSMA-617 whereas 4/43 (9%), 13/43 (30%) and 5/43 (12%) underwent 1, 2 and 3 cycles. PSA decline of ≥50% was observed in 11/43 of patients (26%) after 2 cycles and in 16/43 (37%) at any time (best PSA response). 9/43 (21%) had a PSA decline of ≥90% and 23/43 (53%) had any PSA decline (>0%). After a median follow-up of 19.5 months the median OS was 14.8, 15.7 and 13.5 months in the whole cohort, the 6.0 GBq and 7.4 GBq treatment arms, respectively (p=0.68). Patients showing a PSA decline of ≥50% after 2 cycles and at any time had a longer OS: median 20.1 months vs. 13.6 (p=0.091) and 20.1 vs. 11.6 (p=0.002), respectively. Conclusions: In this post-hoc analysis of a single-site cohort of 43 patients included in a prospective phase II trial the median OS after 177Lu-PSMA-617 molecular radiotherapy in patients with progressive mCRPC was 14.8 months. There was no difference of efficacy between the 6.0 GBq and 7.4 GBq treatment arms. Clinical trial information: NCT03042312 .

Trop-2 expression on treatment resistant cancer cells in castrate-resistant prostate cancer (CRPC) as a predictive biomarker for targeted therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5045-5045
Author(s):  
Kimberly Peihsi Ku ◽  
Joshua Michael Lang ◽  
Jamie Sperger ◽  
Scott Dehm ◽  
Manish Kohli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Trial ◽  
Splice Variant ◽  
Splice Variants ◽  
Predictive Biomarker ◽  
Antibody Drug Conjugate ◽  
Neuroendocrine Markers ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

5045 Background: Trophoblastic cell-surface antigen (Trop-2) is a transmembrane glycoprotein that is highly expressed in many solid tumors. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate of an anti-Trop-2 humanized antibody with SN-38. Early clinical trials have shown high response rates in a broad range of diseases including triple negative breast and urothelial cancers. We evaluated Trop-2 expression in tumor biopsies and circulating tumor cells (CTCs) from men with mCRPC (metastatic castrate-resistant prostate cancer). Methods: Trop-2 expression was evaluated from mCRPC biopsies from patients (Pts) treated with abiraterone acetate (AA) on the PROMOTE clinical trial, CTCs from a separate cohort treated with either enzalutamide or AA. Trop-2 CTCs were compared with EpCAM captured CTCs using a microscale technology termed the VERSA (Vertical Exclusion-based Rare Sample Analysis) platform to compare protein and gene expression signatures of resistance to these agents. Results: RNA sequencing identified Trop-2 gene expression in > 70% of metastatic biopsies. The AR splice variant V7 was found in 48 biopsies that also expressed Trop-2. Trop-2 expression was not altered by treatment with AA at 12 weeks. The number of CTCs captured from 25 pts with Trop-2 or EpCAM were closely correlated (R2= 0.84). Gene expression analysis showed similar patterns of expression for the TROP-2 and EPCAM captured cells. AR splice variant expression (AR-V7, AR-V9) in Trop-2 and EpCAM CTCs was detected in 33% of patients. Expression of neuroendocrine markers was identified in 40% of Trop-2 CTCs. Conclusions: Trop-2 is frequently expressed in mCRPC and co-expressed in tumors that express AR splice variants. Trop-2 CTCs are detected in CRPC pts previously treated with AA or Enzalutamide that also express multiple AR splice variants and neuroendocrine markers. The results support Trop-2 expression as predictive biomarker of sensitivity to targeted therapies tumors resistant to AA or Enzalutamide. Men with mCRPC are being enrolled on a Phase I trial with IMMU-132, and multi-site Phase II clinical trial in men who have progressed on AA or Enzalutamide is being finalized.

Phase II trial of intravenous carboplatin (C), oral everolimus (E), and prednisone (P) in docetaxel-pretreated (DP) metastatic castrate-resistant prostate cancer (mCRPC): A Prostate Cancer Clinical Trials Consortium study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5041-5041
Author(s):  
Muthu Kumaran Veeraputhiran ◽  
Daniel H. Shevrin ◽  
Mark N. Stein ◽  
Lance K. Heilbrun ◽  
Daryn Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Once Daily ◽  
Secondary Endpoints ◽  
Castrate Resistant Prostate Cancer ◽  
Median Area ◽  
Grade 3 ◽  
Castrate Resistant ◽  
Clinical Trial Information

5041 Background: A phase II clinical trial was conducted of the combination of C and E due to the synergy noted. Methods: The primary endpoint was time to progression (TTP). Intravenous C at a target AUC of 5 on day 1, and oral E 5mg once daily and P 5mg twice daily were administered in 21 day cycles. PSA was assessed every 21 days and radiologic response was assessed every 3 cycles. Secondary endpoints included overall survival (OS), the correlation of TTP with phosphorylated (p) mTOR, pAKT, p70S6, and circulating tumor cells (CTC). A 1-stage study design assumed: a reference median TTP = 1.5 months; 1-sided alpha = 0.15; and power = 0.90, requiring 26 patients (pts). Results: 26 pts enrolled; median age 69 years (range 54-86) ;8 African American and 18 Caucasians. Median pretherapy PSA was 190 ng/ml (range 13 - 2174). 18 pts (69%) each had bone pain and Gleason score > 8. 125 cycles have been administered; median 3 cycles (range 1 - 16). Predominant grade 3 or 4 toxicities were thrombocytopenia in 8 pts, pulmonary embolism in 2 and neutropenia in 3. No treatment related deaths occurred. 4 (15%) had a > 30% PSA decline and 1 had a >90% PSA decline. 8/19 pts had stable disease but no objective responses in MD. The median TTP and OS were 2.5 months (90% CI: 1.8 - 4.3), and 12.5 months (90% CI: 6.7 - 16.1), respectively. Median area under curves were 5.9 (range, 4.3 – 11.0) and 4.5 (range, 4.1 – 7.1) mg/mL*min with C given alone and in combination with E, respectively. E did not influence pharmacokinetics of C. Median baseline CTC (n=18) was 30 (range 0-2372). 5/18 pts had favorable CTC (CTC<5/7.5 mL) pretherapy. Patients with TTP >18 weeks had reduction in post-therapy CTC with a median decrease of 63% (range 11%-100%). Lack of IHC staining for pAKT was noted in 2/2 pts on therapy for > 30 weeks vs increased expression was noted in 8/8 pts on therapy for < 9 weeks. Testing for TSC1 mutation is planned and will be reported. Conclusions: The combination was tolerable but revealed modest clinical efficacy. Biomarker evaluations such as pAKT may help identify a subset likely to benefit from mTOR inhibitor strategy in mCRPC. Clinical trial information: NCT01051570.

RESIST-PC phase 2 trial: 177Lu-PSMA-617 radionuclide therapy for metastatic castrate-resistant prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5028-5028 ◽  
Author(s):  
Jeremie Calais ◽  
Wolfgang P Fendler ◽  
Matthias Eiber ◽  
MIchael Lassmann ◽  
Magnus Dahlbom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Radionuclide Therapy ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Psma Pet ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

5028 Background: This is an investigator-initiated open-label prospective bi-centric single-arm phase 2 clinical trial (NCT03042312) of 177Lu-PSMA-617 radionuclide therapy in patients with progressive metastatic castrate-resistant prostate cancer (mCRPC). Methods: Patients with progressive mCRPC (biochemical, radiographic or clinical) after ≥1 novel androgen axis drug (NAAD), either chemotherapy (CTX) naïve or post-CTX, with sufficient bone marrow reserve and normal kidney function were eligible. All patients underwent a screening PSMA PET/CT to confirm target expression. Patients received up to 4 cycles of 177Lu-PSMA-617 every 8±1 weeks and were randomized into 2 treatment activities groups (6.0 or 7.4 GBq). Kidney dosimetry was performed for the first cycle. Efficacy was defined as serum PSA decline of ≥50% from baseline at 12 weeks and served as primary endpoint. Results: 64 patients (median PSA 75 ng/ml; range 0.5-2425) were included in the study. 20% were CTX naïve while 80% were post-CTX (1.9 CTX regimens on average, range 1-4). 45% completed 4 cycles of 177Lu-PSMA-617. Androgen deprivation therapy was given concomitantly in 83%, NAAD in 23% and immunotherapy in 6%. PSA decline of ≥50% was observed in 23% of patients at 12 weeks and in 38% of patients at any time (best PSA response). The median time to best PSA response was 22 weeks (range 6-49 weeks). 16% had a PSA decline of ≥90% and 59% had any PSA decline ( > 0%). Mild and transient (CTCAE grade 1-2) side effects included xerostomia (72%), nausea/vomiting (69%) and bowel movement disorders (45%). CTCAE grade 3 toxicity included nausea/vomiting (6%), anemia (8%), leukopenia (5%), kidney failure (3%), thrombocytopenia (3%), and neutropenia (3%). The mean kidney dose was 2.7 Gy for the first cycle (range 0.9-5.9) i.e. 0.4 Gy/GBq (range 0.15-0.9). There was no difference between the efficacy and toxicity for the 6.0 GBq (n = 23) and 7.4 GBq (n = 41) treatment arms. Conclusions: 177Lu-PSMA-617 radionuclide therapy is well tolerated in patients with progressive mCRPC. PSA declined by ≥50% in 38% of patients. The best PSA response rate occurred after 3 cycles. Updated data will be provided at the time of the conference. Clinical trial information: NCT03042312.

A phase Ib/IIa study of rucaparib (PARP inhibitor) combined with nivolumab in metastatic castrate-resistant prostate cancer and advanced/recurrent endometrial cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2663-TPS2663
Author(s):  
Raanan Alter ◽  
Gini F. Fleming ◽  
Walter Michael Stadler ◽  
Akash Patnaik
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Combination Therapy ◽  
Parp Inhibitor ◽  
Primary Objective ◽  
Parp Inhibition ◽  
Wide Range ◽  
Castrate Resistant Prostate Cancer ◽  
Endometrial Cancers ◽  
Castrate Resistant

TPS2663 Background: Immune checkpoint blockade (ICB) antibodies have made a major impact in a wide range of cancers. However, only subsets of patients across all malignancies benefit from ICB. In particular, metastatic castrate-resistant prostate cancer (mCRPC) and advanced endometrial cancers (EC) have shown very limited responses to ICB. The central hypothesis of this trial is that the combination of PARP inhibitor (rucaparib) with PD-1 inhibitor (nivolumab) will enhance ICB efficacy in mCRPC and mEC patients. Given that PTEN loss has also been associated with poor response to ICB, a secondary hypothesis of this study is that the combination therapy will have differing efficacy based on the PTEN mutation status of the tumor. Methods: This is an investigator-initiated Phase 1b/IIa clinical trial of rucaparib and nivolumab singly and in combination, in mCRPC and mEC patients. Patients are randomized to one of three arms – rucaparib, nivolumab, or both drugs in combination for 4 weeks. Metastatic biopsy samples are collected at baseline and after 4 weeks on treatment, after which all arms will switch to combination therapy. The primary objective is to assess feasibility of the combination, and to elucidate changes in immune infiltrates by Nanostring RNA sequencing, multiplex immunofluorescence, 3D mapping, IHC, and flow cytometry. Secondary objectives are to assess clinical response, and correlate changes in TME with PTEN status. We have currently enrolled 4 patients to the study, and collected pre- and 4 week on-treatment biopsies. This study presents an opportunity for in-depth TME analysis that will enable the delineation of the effects of PARP inhibition singly and in combination with PD-1 blockade, on immune subsets within the TME. The correlative analyses will also lead to the discovery of novel biomarkers of response/resistance, and suggest additional immunooncology combinations for specific molecular subsets of prostate and endometrial cancers. Clinical trial information: NCT03572478.

scholarly journals A tertiary care audit of using abiraterone acetate in patients of metastatic castrate-resistant prostate cancer

2020 ◽  
Vol 09 (01) ◽  
pp. 23-26
Author(s):  
Amit Joshi ◽  
Sameer Shrirangwar ◽  
Vanita Noronha ◽  
Nilesh Sable ◽  
Archi Agarwal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Tertiary Care ◽  
Abiraterone Acetate ◽  
Clinical Trial Setting ◽  
Care Institute ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Clinical Records ◽  
Trial Setting

Abstract Introduction: This is a retrospective analysis to assess the safety and efficacy of abiraterone acetate (AA) in metastatic castrate-resistant prostate cancer (mCRPC) patients treated at tertiary care institute. Materials and Methods: The clinical records of mCRPC patients treated with AA at our tertiary care institute between July 2013 and December 2015 were reviewed. The treatment efficacy, toxicities, and its determinants were analyzed. Results: A total of 59 mCRPC patients treated with AA were reviewed, of whom 37 were chemo-naive and 22 had received prior chemotherapy (postchemo). The median follow-up duration was 10.0/15.0 months for chemo-naïve/postchemotherapy patients. 43.2%/36.36% of chemo-naive/postchemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 15/7.8 months and 10/5.3 months for chemo-naive/postchemo patients, respectively. Median time to best prostate-specific antigen response was 3.4 months. Abiraterone was relatively well tolerated with no grade 4 toxicity or treatment-related death. We found the presence of previous taxene use and baseline symptoms to be significantly determinant of OS with abiraterone. Conclusion: The present study reported the efficacy of abiraterone in both chemo-naïve and postchemo patients of mCRPC outside clinical trial setting. We found lower OS and PFS with abiraterone as compared to that reported in the clinical trial setting in both chemo-naïve and postchemo patients, and particularly in those patients with the visceral disease, and further clinical trial for abiraterone in this subgroup of patients is warranted.

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