A multicenter phase IIb trial to evaluate the efficacy and tolerability of ModraDoc006/r in subjects with metastatic castration-resistant prostate cancer (mCRPC), suitable for treatment with a taxane (NCT04028388).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS268-TPS268
Author(s):  
Ulka N. Vaishampayan ◽  
Edwin J. De Wit ◽  
Neal D. Shore ◽  
Robert Dreicer ◽  
Daniel J. George ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Oral Prednisone ◽  
Objective Response ◽  
Cancer Therapeutics ◽  
Standard Of Care ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Oral Tablet ◽  
Patient Reported

TPS268 Background: Docetaxel IV and prednisone is a standard of care in mCRPC with demonstrated overall survival benefit. ModraDoc006 is a novel oral tablet formulation of docetaxel and to enhance bioavailability, it is co-administered with ritonavir (/r), an inhibitor of cytochrome p450 3A4 and P-glycoprotein. The oral combination, denoted as ModraDoc006/r, could be preferable due to patient convenience and elimination of infusion reactions and prophylactic steroids administration. Due to its weekly administration and exposure levels, increased efficacy may be demonstrated. Methods: The study is an open label 1:1 randomized phase 2b trial of ModraDoc006/r bi-daily QW versus docetaxel IV 75 mg/m2 Q3W. Thirty (30) mg ModraDoc006 combined with 200 mg /r in morning and 20 mg ModraDoc006 with 100 mg /r in evening is administered on days 1, 8 and 15 of a 21 day cycle. Safety and preliminary efficacy of ModraDoc006/r have been established in a phase Ib trial in mCRPC pts. All patients will receive 5 mg oral prednisone twice daily. Treatment is continued until progression, unacceptable toxicity or patient wish. mCRPC pts with measurable disease per RECIST 1.1, suitable for docetaxel therapy, are eligible. No prior treatment with taxanes is allowed. Primary objective is objective response rate (ORR) as assessed by investigators. Secondary objectives include PSA response, PSA-PFS, time to skeletal related events and progression, duration of response, disease control rate and safety assessments. Patient reported outcomes and health-related quality of life will be captured with treatment satisfaction and FACT-P questionnaires. It is expected that ModraDoc006/r will be at least as effective as docetaxel IV. A sample size of 50 evaluable pts per arm will evaluate an estimated ORR of 25% in each arm, with a 5% two-sided alpha and power of 83.7%. Conclusions: ModraDoc006/r represents an advance in prostate cancer therapeutics with convenience of oral administration, reduced myelosuppressive toxicity and potential improved efficacy over IV docetaxel. Clinical trial information: NCT04028388.

Phase IIb trial of oral ModraDoc006/r as a tolerable and effective option in comparison with intravenous docetaxel in metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 132-132
Author(s):  
Ulka N. Vaishampayan ◽  
Marianne Keessen ◽  
Neal D. Shore ◽  
Elisabeth I. Heath ◽  
Robert Dreicer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Oral Prednisone ◽  
Objective Response ◽  
Comparable Efficacy ◽  
Point Estimate ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Oral Tablet ◽  
Study Results ◽  
Patient Reported

132 Background: ModraDoc006 is a novel, oral tablet formulation of docetaxel. To enhance bioavailability, it is co-administered with ritonavir (r), an inhibitor of cytochrome P450 3A4 and P-glycoprotein. The oral combination, denoted ModraDoc006/r, has potential advantages in terms of patient convenience, elimination of infusion-related reactions and avoiding prophylactic steroid administration, as well as safety benefits. Safety and preliminary efficacy of ModraDoc006/r in mCRPC were established in a prior phase Ib trial. Methods: This is an open label 1:1 randomized phase IIb trial of ModraDoc006/r bi-daily once weekly (BIDW) regimen versus IV docetaxel 75 mg/m2 q day 21. Initially, BIDW 30-20 mg ModraDoc006 combined with 200-100 mg ritonavir was administered on days 1, 8 and 15 of a 21-day cycle. After 39 patients, the dose of ModraDoc006 was reduced to 20-20 mg BIDW to improve GI tolerability. All patients received 5 mg oral prednisone BID. Imaging is obtained every 8-9 weeks for the first 24 weeks, every 12 weeks thereafter. Initially mCRPC patients with RECIST 1.1 measurable disease were eligible; this was amended to evaluable disease per Prostate Cancer Working Group 3 (PCWG3) to allow for wider recruitment. No prior taxane therapy is allowed. The primary efficacy endpoint is radiographic progression free survival (rPFS) per PCWG3 criteria. Secondary objectives include objective response rate, PSA-PFS, time to skeletal related events, disease control rate, duration of response and safety. Patient reported outcomes, QoL and FACT-P questionnaires are assessed. It is expected that ModraDoc006/r will be as effective as IV docetaxel. A sample size of approximately 50 evaluable patients per arm will provide a point estimate of the primary endpoint of rPFS for this study. Results: At the data cut-off of 30 Nov 2020, 90 patients were enrolled in US and EU: 44 patients had been randomized to IV docetaxel and 46 to ModraDoc006/r, with 58 patients currently on treatment. Preliminary PSA response rates and rPFS were noted to be comparable in both treatment arms. ModraDoc006/r was mainly associated with mild and reversible GI-toxicity, of which grade and incidence were reduced at 20-20 mg compared to the initial dose-level of 30-20 mg ModraDoc006. Myelosuppression and neurotoxicity were low to negligible in the ModraDoc006/r arm, with low accompanying levels of alopecia. Conclusions: Adverse events of cytopenias and alopecia were lower with ModraDoc006/r, and preliminary efficacy appears comparable in both arms. Oral chemotherapy option has become critically important during the COVID-19 pandemic. Preliminary data reveals that ModraDoc006/r is an attractive oral option in mCRPC with favorable toxicity profile and comparable efficacy. Clinical trial information: NCT04028388.

A multicenter, randomized, controlled phase II study: Efficacy and safety of PSMA-targeted radioligand therapy I-131-1095 (1095) plus enzalutamide (enza) in 18F-DCFPyL PSMA scan avid, metastatic castration-resistant prostate cancer (mCRPC) patients post-abiraterone (abi) progression (ARROW).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5596-TPS5596
Author(s):  
Evan Y. Yu ◽  
David Laidley ◽  
Frederic Pouliot ◽  
Stephan Probst ◽  
Robert Sabbagh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
Radiographic Progression ◽  
Objective Response ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Open Label ◽  
Recist 1.1 ◽  
Modified Recist

TPS5596 Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689 .

A multicenter, randomized, controlled phase II study: Efficacy and safety of PSMA-targeted radioligand therapy I-131-1095 (1095) plus enzalutamide (enza) in 18F-DCFPyL PSMA scan avid, metastatic castration-resistant prostate cancer (mCRPC) patients post-abiraterone (abi) progression (ARROW).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS260-TPS260
Author(s):  
Evan Y. Yu ◽  
David Laidley ◽  
Frederic Pouliot ◽  
Stephan Probst ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
Radiographic Progression ◽  
Objective Response ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Open Label ◽  
Recist 1.1 ◽  
Modified Recist

TPS260 Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689.

A multicenter, randomized, controlled phase II study: Efficacy and safety of PSMA-targeted radioligand therapy I-131-1095 (1095) plus enzalutamide (enza) in 18F-DCFPyL PSMA scan avid, metastatic castration-resistant prostate cancer (mCRPC) patients post-abiraterone (abi) progression (ARROW).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS187-TPS187
Author(s):  
A. Oliver Sartor ◽  
David Laidley ◽  
Frederic Pouliot ◽  
Stephan Probst ◽  
Robert Sabbagh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Open Label ◽  
Recist 1.1 ◽  
Modified Recist

TPS187 Background: PSMA is a transmembrane glycoprotein overexpressed in prostate cancer (PC) and further upregulated in castrate resistant disease. 1095 is a novel PSMA-targeted small molecule radioligand therapeutic that binds to the extracellular domain of PSMA selectively with high affinity, internalized, and delivers a targeted lethal radiation dose to PC cells. 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown robust diagnostic performance for detecting recurrent and metastatic PC. In the ARROW study, pts must demonstrate 18F-DCFPyL avidity prior to 1095 treatment. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at multiple sites in the US and Canada. Eligible male pts must have metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional doses administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Due to the COVID-19 pandemic, enrollment was halted in April 2020 but is reopening in October 2020. Clinical trial information: NCT03939689.

VISION: An international, prospective, open-label, multicenter, randomized phase 3 study of 177Lu-PSMA-617 in the treatment of patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5099-TPS5099 ◽  
Author(s):  
A. Oliver Sartor ◽  
Michael J. Morris ◽  
Bernd J Krause
Keyword(s):  
Prostate Cancer ◽  
Alternative Hypothesis ◽  
Standard Of Care ◽  
Primary Objective ◽  
Therapeutic Drug ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Phase 3 ◽  
Eligibility Criteria ◽  
Castration Resistant

TPS5099 Background: The novel therapeutic drug 177Lu-PSMA-617 is a prostate specific membrane antigen (PSMA) targeting agent to deliver radionuclide therapy for the treatment of pts with metastatic castration resistant prostate cancer. Based on preclinical data that demonstrated high PSMA binding affinity & compound internalization, prolonged tumor uptake, rapid kidney clearance, & high tumor-to-background ratio, 177Lu-PSMA-617 proceeded into clinical development. Preliminary clinical evidence indicates 177Lu-PSMA-617 may demonstrate clinical benefit in pts with mCRPC in a setting where pts had no recommended standard of care. This Phase 3 study will assess the efficacy of 177Lu-PSMA-617 in patients with progressive PSMA-positive mCRPC by measuring overall survival (OS) and radiographic progression free survival (rPFS) in a randomized, prospective, open-label trial. Methods: The primary objective of this study is to compare the 2 alternative endpoints of rPFS & OS in pts with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/standard of care vs pts treated with best supportive/best standard of care alone. Eligibility criteria are: PSMA expressing tumor; prior exposure to a taxane and novel androgen axis drug. Pts will be randomized in a 2:1 ratio in favor of the investigational arm with stratification factors of LDH, liver disease, ECOG score, and use of NAAD at time of randomization as a standard of care. Under the alternative hypothesis, median OS on active is assumed to be 13.7 mo for a HR of 0.7306 and rPFS on the active is assumed to be 6 mo for a HR of 0.67. Planned enrollment for this study is 750 patients. Enrollment began in June 2018 and continues; the IDMC last reviewed the trial for safety in January 2019 and suggested that the trial continue as planned. Clinical trial information: NCT03511664.

Phase I study of CNTO 95, a fully human monoclonal antibody to αv integrins, docetaxel, and prednisone in hormone refractory prostate cancer patients (HRPCP)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15595-15595
Author(s):  
F. M. Chu ◽  
J. Picus ◽  
M. Mata ◽  
C. Kopacynski ◽  
B. Foster ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Standard Dose ◽  
Human Monoclonal Antibody ◽  
Oral Prednisone ◽  
Standard Of Care ◽  
Primary Objective ◽  
Hormone Refractory ◽  
Grade 3 ◽  
Cancer Tissues ◽  
Group 1

15595 Background: CNTO 95 has demonstrated preclinical antitumor activity through binding to multiple av integrins, resulting in growth inhibition indirectly through anti-angiogenic effects as well as directly by inhibiting tumor cell proliferation. The target, av integrins, has been demonstrated by immunohistochemistry in a large proportion of human prostate cancer tissues. Docetaxel and prednisone have become a standard of care for HRPCP. The primary objective of this study was to evaluate the safety of combining CNTO 95 with this standard. Methods: Patients received day 1 infusions of 75 mg/m2 docetaxel together with twice daily oral prednisone in every 3 week cycles, with weekly infusions of either 5 or 10 mg/kg of CNTO 95 for 7 weeks beginning with the second docetaxel cycle, then CNTO 95 on the days of docetaxel thereafter. Patients were monitored for safety and PSA. Radiologic tumor assessments were performed at least every 4 cycles. Results: Six patients have received docetaxel and prednisone with CNTO 95 at either 5 mg/kg (n=3) or 10 mg/kg (n=3). In the 5 mg/kg group, 1 received 8 cycles then withdrew consent because of fluctuating PSA levels; 1 received 9 cycles then had soft tissue disease progression; and 1 has completed 9 cycles and remains on study treatment. In the 10 mg/kg group, all patients remain on study and have received 7, 6, and 6 cycles of treatment, respectively. There were no unexpected toxicities and only one Grade 3 toxicity (febrile neutropenia) attributed to docetaxel. A 50% decline in PSA occurred in 1 patient treated in the 10 mg/kg group. Conclusions: The combination of standard dose docetaxel and prednisone with 10 mg/kg of CNTO 95 was well tolerated and 3 new patients are planned to be treated with these doses on this study. Further study is warranted. [Table: see text]

Pilot study of veliparib (ABT-888) with temozolomide (TMZ) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Maha Hussain ◽  
Michael Anthony Carducci ◽  
Susan F. Slovin ◽  
Jeremy Paul Cetnar ◽  
Jiang Qian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Type I Error ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Type I ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Clinically Significant

224 Background: Castration-resistant PC tumors exhibit increased PARP activity (critical enzymes for DNA damage repair). Veliparib is a novel, oral, potent inhibitor of PARP-1 and PARP-2. Preclinically, resistance to oral TMZ treatment in the PC3-Luc prostate cancer mouse model was reversed when mice were treated with veliparib. Based on the synergistic interaction, we evaluated the efficacy and safety of veliparib + TMZ in mCRPC pts. Methods: Eligible pts had mCRPC, PSA>2 ng/mL, progressed on at least one docetaxel based therapy and adequate organ function. Pts received veliparib 40 mg BID Days (D) 1-7 and TMZ D1-5 in 28D cycle (C) until disease progression (PD) or unacceptable toxicities. Tumor response was assessed every 8 weeks. Primary objective: Efficacy based on rate of PSA decline of 30% or greater. Secondary objectives: safety, RECIST objective response rate, progression-free survival (PFS), overall survival (OS) and biomarker analyses. A sample size of 25 pts provided 76% power to differentiate between PSA response rates of 5 and 20% at 1-sided type I error rate of 0.1. Results: 26 pts were enrolled; median age 67 years [55, 81]; median baseline PSA 107 ng/ml (6.9, 4584.4); 7/26 (27%) had 2 prior therapies. Median Cs of veliparib + TMZ received were 2 (range 1–9). Most frequent treatment related adverse events (AE) were fatigue (50%), nausea (38%) and constipation (23%). Grade 3/4 AEs in >10% of pts was thrombocytopenia (15%). All pts are off therapy. 25 pts were PSA response evaluable; 2 pts had a confirmed PSA response; 1 pt had a 37% decrease in PSA while the other pt had a 96% decrease in PSA and a 40% reduction in tumor size. 4/25 pts had stable disease for a minimum of 4 months (m). Median PFS was 2.1 m [95% CI: 1.8, 3.9]; 11/26 pts have died with median OS of 9.1 m [95% CI: 5.5, 11.7]. There was a negative correlation between change from baseline in circulating tumor cells and PFS. Conclusions: Veliparib + TMZ were well tolerated with evidence of some activity. Due to lack of activity of TMZ in CRPC,veliparib-induced potentiation of TMZ may not be clinically significant. Other combinations will be explored with higher doses of veliparib. Biomarker data will be presented.

Modulation of plasma lipidomic signature in metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS331-TPS331
Author(s):  
Blossom Mak ◽  
Kate Lynette Mahon ◽  
Martin R. Stockler ◽  
Anthony M. Joshua ◽  
Alison Yan Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lipid Profile ◽  
Primary Objective ◽  
Lipid Lowering ◽  
Castration Resistant Prostate Cancer ◽  
Prognostic Signature ◽  
Open Label ◽  
Metabolic Characteristics ◽  
Type 1 Error ◽  
The Poor

TPS331 Background: Altered lipid metabolism and its impact on prostate cancer (PC) is increasingly recognised, in light of the association between obesity and worse PC outcomes. Our exploratory study was the first to identify baseline plasma lipidomic profiles in men with mCRPC commencing docetaxel that were associated with survival. A prognostic three-lipid signature was derived, consisting of ceramide, sphingomyelin and phosphatidylcholine (HR 4.8, 95% CI 2.06-11.1, p = 0.0003). This signature was independently prognostic when modelled with clinicopathological factors and metabolic characteristics. A key question is whether therapeutic modulation of a patient’s lipid profile is possible. Statins significantly reduce the plasma levels of ceramides, sphingomyelin and cholesterol in cardiovascular disease, suggesting that this therapy could change the poor prognostic lipid profile of mCRPC patients. This trial assesses whether addition of simvastatin to docetaxel for mCRPC can reverse the poor prognostic lipid signature with the aim of developing a precision medicine strategy for metabolic targeting. Methods: This investigator-initiated, multi-centre, open-label, single arm, pilot study enrols patients with mCRPC commencing docetaxel for disease progression, not already receiving a lipid-lowering agent. Patients are treated with simvastatin 40mg orally once daily for 12 weeks, commencing on day 1 of the first cycle of docetaxel. Blood is taken at baseline and after 12 weeks of simvastatin and the plasma lipidomic profile is determined using liquid chromatography and electrospray ionisation-tandem mass spectrometry. The lipidomic profile is classified as either good or poor prognostic as per our three-lipid signature model derived by logistic regression. The primary objective is to assess the rates of conversion from a poor prognostic lipid signature to good prognostic after simvastatin. A sample size of 60 men provides over 90% power, with a 1-sided type 1 error of 10%, to detect conversion to the good prognostic signature in 50% of patients, assuming 25% of patients have the poor prognostic signature at baseline as previously detected. To date, 6 patients have been enrolled to the trial. Clinical trial information: ACTRN12617000965303.

A randomized, open-label phase II study of nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated metastatic pancreatic adenocarcinoma (mPAC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS482-TPS482 ◽  
Author(s):  
Andrew Dean ◽  
Li-Tzong Chen ◽  
Ramesh K. Ramanathan ◽  
Sarah Blanchette ◽  
Bruce Belanger ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
Secondary Endpoints

TPS482 Background: Two combination chemotherapy regimens have emerged as standard of care options for first-line treatment of mPAC: 5-fluorouracil (5-FU)/leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX), and nab-paclitaxel + gemcitabine. Nal-IRI (MM-398) is a nanoliposomal formulation of irinotecan. In a randomized phase 3 study (NAPOLI-1), of patients with mPAC who had been previously treated with gemcitabine-based therapy, nal-IRI + 5-FU/LV demonstrated its safety and significant clinical activity, increasing overall survival (OS) and progression-free survival (PFS) relative to 5-FU/LV. The goal of this current study is to determine the preliminary safety and efficacy of nal-IRI+ + 5-FU/LV with or without oxaliplatin as compared to nab-paclitaxel + gemcitabine in previously untreated patients with mPAC. Methods: This open-label, phase 2 comparative study will be conducted in two parts. Part 1 is a safety run-in of a nal-IRI+5-FU/LV + oxaliplatin regimen. The safety run-in will enroll small cohorts of patients following a traditional 3 + 3 dose escalation design to confirm the target dose of oxaliplatin (n = ~6-18). The primary objective of Part 1 is the safety and tolerability of nal-IRI + 5FU/LV + oxaliplatin. Part 2 is a randomized, efficacy study of a nal-IRI + 5-FU/LV + oxaliplatin regimen (Arm 1), the nal-IRI + 5-FU/LV combination that previously demonstrated efficacy in the NAPOLI-1 trial (Arm 2), versus a nab-paclitaxel + gemcitabine control arm (Arm 3) (n = ~156-168). The primary objective of Part 2 is to assess the efficacy of nal-IRI-containing regimens in first-line mPAC patients compared to nab-paclitaxel + gemcitabine using the progression-free survival (PFS) rate at 24 weeks as the primary endpoint. Secondary of part 1 is a PK study and Part 2 secondary endpoints will include OS, PFS, objective response rate (per RECIST, v1.1), decrease in CA19-9 levels and quality of life assessments. Clinical trial information: NCT02551991.

VISION: An international, prospective, open-label, multicenter, randomized phase III study of 177Lu-PSMA-617 in the treatment of patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS259-TPS259 ◽  
Author(s):  
A. Oliver Sartor ◽  
Michael J. Morris ◽  
Richard Messman ◽  
Bernd J. Krause
Keyword(s):  
Positron Emission Tomography Imaging ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Phase Iii ◽  
Therapeutic Drug ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Eligibility Criteria ◽  
Positron Emission

TPS259 Background: The novel therapeutic drug 177Lu-PSMA-617 is a prostate-specific membrane antigen (PSMA) targeting agent that is used to deliver radionuclide therapy for the treatment of patients with mCRPC. Based on preclinical data that demonstrated high PSMA binding affinity and internalization, prolonged tumor uptake, rapid kidney clearance, and high tumor-to-background ratio, 177Lu-PSMA-617 proceeded into clinical development. Preliminary clinical data indicates that 177Lu-PSMA-617 may demonstrate clinical benefit in patients with mCRPC in a setting where patients had no clear standard of care. VISION (NCT03511664) is a phase 3 study designed to assess the efficacy of 177Lu-PSMA-617 in patients with PSMA-positive mCRPC. Methods: Patients were randomized 2:1 to receive best standard of care with or without 177Lu-PSMA-617. Eligibility criteria were: PSMA expressing tumor assessed by PSMA positron emission tomography imaging; prior exposure to a taxane and a novel androgen axis inhibitor (NAAI). The primary objective of this study is to compare the two alternative endpoints of progression-free survival (rPFS) and overall survival (OS). Stratification factors include lactate dehydrogenase, liver metastasis, ECOG PS, and use of an NAAI at time of randomization. On active treatment, median OS is assumed to be 13.7 months with a hazard ratio (HR) of 0.7306, and rPFS is assumed to be 6 months with an HR of 0.67. Enrollment began in June 2018 and the target of 814 patients has been reached. Clinical trial information: NCT03511664.

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