Phase II study of regorafenib (Reg) in patients with previously treated advanced pancreatic cancer (APC).

e15751 Background: APC that has progressed after treatment with gemcitabine has a dismal prognosis and novel treatment approaches are needed. Reg is a potent oral inhibitor of VEGFR 1-3, PDGFR, TIE-2, FGFR-1, KIT, and the RAF kinases, and has activity in pancreatic xenograft models. We tested the activity of Reg in patients (pts) with refractory APC. Methods: This single arm, single center phase II study evaluated Reg (120mg/d, for 21 days, followed by 7-day break, with escalation to 160mg after the 1st cycle if tolerated) in pts with metastatic pancreatic cancer whose disease had progressed after at least one prior line of therapy and treatment with gemcitabine. Pts underwent radiographic evaluation every 2 cycles. The primary endpoint was 16-wk PFS. Kaplan Meier techniques were used to estimate PFS and OS. Serum tumor MUC1 antigen (tMUC1) concentrations were measured at baseline, end of cycle 1, and off-treatment using the TAB 004 antibody (Agkura Personal Score blood test, OncoTAb, Inc). Relative change of tMUC1 from baseline to end of cycle 1 was compared between those with and without 16-wk disease control. Results: 20 pts were enrolled into the study. Median age = 65 (47-79), and 80% (16/20) had 2 or more prior lines of therapy for advanced disease. Landmark 16 wk PFS = 10% (2/20), crossing a predefined futility boundary to demonstrate 20% improvement over historical controls with BSC. ORR was 5% (1/20), and DCR at 8 wks was 20% (4/20). Median PFS was 6.1 wks (95% CI: 2.9 – 7.1), and median OS was 9.4 wks (95% CI: 8.1 – 17.0). 10% of pts (2/20) had protocol defined Reg dose escalation to 160mg, and 30% (6/20) had dose reduction to 80mg. The most frequent grade 3-4 adverse events included hyponatremia (35%), fatigue (20%), and hypoalbuminemia (20%). Baseline tMUC1 varied substantially, mean 69.6ug/mL, median 51.3ug/mL (10.8 – 310.5). Serum tMUC1 decreased by a mean of 20.8% in the pts with disease control at 16 wks (n = 2), but increased by 65% (mean) in pts with disease progression or death within 16 wks (n = 13, p = 0.048). Conclusions: Reg has minimal activity as a single agent in pts with heavily treated APC. Serum tMUC1 levels measured by TAB 004 antibody may be a novel tumor marker in this disease. Different treatment approaches are needed. Clinical trial information: NCT02080260.

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Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2

Journal of Clinical Oncology ◽

10.1200/jco.21.00003 ◽

2021 ◽

pp. JCO.21.00003

Author(s):

Kim A. Reiss ◽

Rosemarie Mick ◽

Mark H. O'Hara ◽

Ursina Teitelbaum ◽

Thomas B. Karasic ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Maintenance Therapy ◽

Disease Control ◽

Phase Ii ◽

Phase Ii Study ◽

Advanced Pancreatic Cancer ◽

Platinum Sensitive ◽

Duration Of Response ◽

Brca1 Brca2

PURPOSE Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline BRCA1 or BRCA2 pathogenic variant (PV). This investigator-initiated, single-arm phase II study assessed the role of the PARPi rucaparib as maintenance therapy in advanced PC with germline or somatic PV in BRCA1, BRCA2, or PALB2. PATIENTS AND METHODS Eligible patients had advanced PC; germline (g) or somatic (s) PVs in BRCA1, BRCA2, or PALB2, and received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was discontinued and patients received rucaparib 600 mg orally twice a day until progression. The primary end point was the progression-free survival (PFS) rate at 6 months (PFS6). Secondary end points included safety, ORR, disease control rate, duration of response, and overall survival. RESULTS Of 46 enrolled patients, 42 were evaluable (27 g BRCA2, seven g BRCA1, six g PALB2, and two s BRCA2). PFS6 was 59.5% (95% CI, 44.6 to 74.4), median PFS was 13.1 months (95% CI, 4.4 to 21.8), and median overall survival was 23.5 months (95% CI, 20 to 27). The PFS at 12 months was 54.8%. ORR of the 36 patients with measurable disease was 41.7% (3 complete responses; 12 partial responses; 95% CI, 25.5 to 59.2), and disease control rate was 66.7% (95% CI, 49.0 to 81.4). Median duration of response was 17.3 months (95% CI, 8.8 to 25.8). Responses occurred in patients with gBRCA2 (41%, 11 out of 27), gPALB2 (50%, 3 out of 6), and sBRCA2 (50%, 1 out of 2). No new safety signals were noted. CONCLUSION Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced PC with a PV in BRCA1, BRCA2, or PALB2. The finding of efficacy in patients with g PALB2 and s BRCA2 PVs expands the population likely to benefit from PARPi beyond g BRCA1/ 2 PV carriers.

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A multinational phase II study of liposome irinotecan (PEP02) for patients with gemcitabine-refractory metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.237 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 237-237 ◽

Cited By ~ 1

Author(s):

A. H. Ko ◽

M. A. Tempero ◽

Y. Shan ◽

W. Su ◽

Y. Lin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Disease Control ◽

Phase Ii ◽

Phase Ii Study ◽

Safety Data ◽

Advanced Pancreatic Cancer ◽

Human Pancreatic Cancer ◽

Free Form ◽

Minor Response ◽

Mouse Xenograft Model

237 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11) that has improved pharmacokinetics and tumor biodistribution of both CPT-11 and its active metabolite-SN38 compared to the free form drug. PEP02 has showed encouraging safety and efficacy in various tumor types, including significant antitumor activity in a human pancreatic cancer L3.6pl orthotopic nude mouse xenograft model. In previous phase I studies, PEP02 either alone or in combination with 5-FU/LV demonstrated prolonged disease control in 5 of 7 (71%) patients (pts) with gemcitabine (GEM)-refractory advanced pancreatic cancer (PC). This phase II study aims to evaluate PEP02 monotherapy as 2nd-line treatment in pts with metastatic, GEM-refractory PC. Methods: Pts were eligible if they had metastatic pancreatic adenocarcinoma, KPS ≥ 70, and progressed following one line of GEM-based therapy. Treatment consisted of PEP02 120 mg/m2 administered as a 90-minute infusion every 3 weeks. A Simon's 2-stage design was used with 16 pts in the first stage and 39 pts in total; primary objective was 3-month survival rate (OS3-month). Results: Between March 2009 and August 2010, 37 pts were enrolled at 3 centers in the U.S. and Taiwan. Characteristics for the first 31 evaluable pts: 13 M/18 F; age 39-82 yrs; 19 Asian/12 Caucasian, KPS 100/90/80/70: 5/14/4/8. Mean number of treatment cycles is 5 (range, 1-22). Disease control rate (minor response + stable disease >2 cycles) is 52%. 8 of 24 pts (33%) with elevated baseline CA19-9 have had >50% biomarker decline. To date, 23/31 pts (74%) have survived > 3 months, with 4 pts still alive after 1 year. Reasons for study discontinuation: 74% progressive disease, 9% drug-related toxicity, 17% other. Preliminary safety data is available for the first stage. Most common G3/4 adverse events included: fatigue (31%), neutropenia (25%), nausea/vomiting (19%), and diarrhea (13%). Conclusions: This study has already met its primary endpoint (predicted OS3-month >65%). PEP02 appears to have both activity and tolerable side effects for pts with metastatic, GEM-refractory PC, and represents a promising option for this pt population with few standard options. [Table: see text]

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