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.

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

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 156-156
Author(s):  
Muthu Kumaran Veeraputhiran ◽  
Daniel H. Shevrin ◽  
Lance K. Heilbrun ◽  
Daryn Smith ◽  
Jing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Mtor Inhibition ◽  
Measurable Disease ◽  
Grade 3 ◽  
And Performance ◽  
Castrate Resistant

156 Background: Platinum based therapies have demonstrated efficacy in DP mCRPC. EVE demonstrated preclinical efficacy in chemotherapy resistant prostate cancer models. Clinical synergy was noted between C and EVE, hence a phase II trial of the combination was conducted. Methods: Primary endpoint was time to progression (TTP). Progression was defined per RECIST criteria for measurable disease (MD), or skeletal event, or > 2 new areas of bone metastases. DP mCRPC patients with adequate renal and liver function, and performance status of 0 or 1 were eligible. Intravenous C at target AUC of 5 on day 1, and oral EVE 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), correlation of TTP and PSA response, with markers such as phopho mTOR, pAKT, p70S6 and circulating tumor cells (CTC). Results: 26 patients (pts) enrolled, including 8 African Americans, and accrual is complete. Median age was 69 years (range 54-86). Median pretherapy PSA was 190 ng/ml (range 13 - 2174). 18 pts (69%) had bone pain. Gleason score was > 8 in 18 pts. 19 pts had measurable disease of which 15 had MD progression, 18 had bone scan progression, and 2 had PSA-only progression. 124 cycles have been administered; median 3 cycles (range 1 - 16). The predominant grade 3 or 4 toxicities were thrombocytopenia in 8 pts, pulmonary embolism in 2 and neutropenia in 3. No treatment related deaths occurred. Of 26 pts who are response evaluable, 4 (15%) had a > 30% PSA decline and 1 had a >90% PSA decline. Of 19 pts with MD, 8 had stable disease and no objective responses were observed. 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. Correlative studies including pharmacokinetic and pharmacodynamic evaluations are ongoing, and will be reported. Conclusions: The combination was tolerable but revealed modest clinical efficacy. Biomarker evaluation may help identify a subset likely to benefit from mTOR inhibition strategy in mCRPC. Clinical trial information: NCT01051570.

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 .

A phase II trial of weekly i.v. KW-2170 in advanced castrate-resistant prostate cancer

2010 ◽  
Vol 6 (4) ◽  
pp. 292-297 ◽  
Author(s):  
Paul L DE SOUZA ◽  
Scott NORTH ◽  
Graeme B BOLGER ◽  
Harris SPIRIDONIDIS ◽  
Robert LIM ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals A phase II study of docetaxel plus lycopene in metastatic castrate resistant prostate cancer

2021 ◽  
Vol 143 ◽  
pp. 112226
Author(s):  
Eric Zhuang ◽  
Edward Uchio ◽  
Michael Lilly ◽  
Xiaolin Zi ◽  
John P. Fruehauf
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Preliminary analysis of a U.S. phase II study of the safety and tolerability of proxalutamide (GT0918) in subjects with mCRPC who had progressed on either abiraterone (Abi) or enzalutamide (Enza).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 99-99
Author(s):  
Nicholas J. Vogelzang ◽  
Richard Levin ◽  
Arash Rezazadeh ◽  
Chandler H. Park ◽  
Britt Haley Bolemon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Lipid Lowering ◽  
Early Discontinuation ◽  
Once Daily ◽  
Experimental Therapies ◽  
Daily Dose ◽  
Grade 3 ◽  
Good Treatment Option ◽  
Recommended Phase Ii Dose ◽  
Clinical Trial Information

99 Background: GT0918, an androgen receptor (AR) antagonist, is a new chemical entity with reduced drug accumulation in the CNS. In a phase I dose escalation trial (NCT02826772), GT0918 was well tolerated with some durable responses in mCRPC patients (pts) who had progressed on ≥2 lines of standard and experimental therapies. This Phase 2 was designed to study the safety and efficacy of GT0918 400 mg vs. 500 mg oral daily in mCRPC pts who had progressed on either Abi or Enza with or without prior docetaxel. Methods: Pts with histologically confirmed mCRPC who had progressed on either Abi or Enza with or without prior docetaxel were eligible and randomized to 400 mg or 500 mg of GT0918 administered once daily orally. Pts continued treatment with GT0918 at their assigned dose until disease progression, intolerable toxicities or withdrawal of consent. PSA and labs were checked monthly. Imaging scans (CT/MRI and bone scan), circulating tumor cells and cf-DNA/RNA were performed every 3 months. Results: 61 pts were enrolled at 9 US sites and randomized 1:1 to 400 mg (n = 31) or 500 mg (n = 30) daily dose. All pts had progressed on either Abi (n = 34) or Enza (n = 27). Most of the reported AEs related to GT0918 were grade 1 or 2 as per CTCAE v4.03, but 22 AEs (5.3%) were reported as grade ≥ 3, such as fatigue, increase ALT/AST, rhabdomyolysis, or muscle weakness. Some AEs were due to drug-drug interaction with lipid-lowering medications leading to early discontinuation (26.2%). As of 5 October 2020, twelve pts finished 6 cycles. Among them, three finished 12 cycles and remained on the treatment. Treatment duration showed more pts in the 400 mg cohort with stable disease (SD) on imaging (9/31 finished 6 cycles) compared to the 500 mg cohort (3/30 finished 6 cycles). Further, all three pts who finished 12 cycles had progressed on Abi indicating that GT0918 might be a good treatment option for pts who had progressed on Abi. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated and resulted in SD in pts who had progressed on either Abi or Enza. The 400 mg/day will be considered as the recommended phase II dose for further clinical trials. GT0918 is warranted for pts failed either Abi or Enza. Clinical trial information: NCT03899467.

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