Oxaliplatin Plus Irinotecan Compared With Irinotecan Alone as Second-Line Treatment After Single-Agent Fluoropyrimidine Therapy for Metastatic Colorectal Carcinoma

2008 ◽  
Vol 26 (28) ◽  
pp. 4544-4550 ◽  
Author(s):  
Daniel G. Haller ◽  
Mace L. Rothenberg ◽  
Alfred O. Wong ◽  
Piotr M. Koralewski ◽  
Wilson H. Miller ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Single Agent ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Sensory Disturbances ◽  
Previously Treated ◽  
Grade 3

Purpose To determine whether irinotecan plus oxaliplatin (IROX) is superior to irinotecan alone in patients with metastatic colorectal cancer (CRC) previously treated with single-agent fluoropyrimidines. Patients and Methods A phase III, randomized, open-label, multicenter study of patients with metastatic or recurrent CRC that had progressed or recurred during or after adjuvant or first-line fluoropyrimidines (fluorouracil/leucovorin or capecitabine, the latter only for metastatic CRC). Patients received IROX (irinotecan 200 mg/m2 plus oxaliplatin 85 mg/m2) or irinotecan alone (350 mg/m2) every 3 weeks. Results At the data cutoff (when 447 of 628 randomly assigned patients had died), median overall survival was 13.4 months (95% CI, 12.4 to 14.7 months) and 11.1 month (95% CI, 10.0 to 12.7 months) in the IROX and irinotecan groups, respectively (hazard ratio = 0.78; 95% CI, 0.65 to 0.94; P = .0072). Overall response rate (22% v 7%, respectively; P < .0001), median time to progression (5.3 v 2.8 months, respectively; P < .0001), and improvement in tumor-related symptoms (32% v 19%, respectively; P = .0072) were also improved with IROX as compared with irinotecan. With the exception of granulocytopenia (25% v 13%), diarrhea (28% v 23%), and sensory disturbances (5% v 0%), grade 3 to 4 toxicities were comparable between the IROX and irinotecan groups, respectively. Conclusion IROX is an effective treatment for metastatic CRC that has progressed after first-line fluoropyrimidine therapy. IROX improves efficacy compared with irinotecan alone, providing an additional option in the postadjuvant or second-line treatment setting for patients who experience treatment failure with single-agent fluoropyrimidine therapy.

Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16036-e16036
Author(s):  
Jerome Fayette ◽  
Valentine Polivka ◽  
Sylvie Chabaud ◽  
Bertrand Favier ◽  
Severine Racadot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Alternative Therapy ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Studies ◽  
Line Chemotherapy

e16036 Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.

scholarly journals Efficacy and Safety of Docetaxel and Sodium Cantharidinate Combination vs. Either Agent Alone as Second-Line Treatment for Advanced/Metastatic NSCLC With Wild-Type or Unknown EGFR Status: An Open-Label, Randomized Controlled, Prospective, Multi-Center Phase III Trial (Cando-L1)

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Wu ◽  
Chao Deng ◽  
Hui Zhang ◽  
Jie Weng ◽  
Youhua Wu ◽  
...  
Keyword(s):  
Single Agent ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Wild Type ◽  
Open Label ◽  
Metastatic Nsclc ◽  
Significant Difference ◽  
Nsclc Patients

Second-line treatment options for advanced/metastatic non-small cell lung cancer (NSCLC) patients are limited. We aimed to evaluate the efficacy and safety of docetaxel/sodium cantharidinate combination vs. either agent alone as second-line treatment for advanced/metastatic NSCLC patients with wild-type or unknown EGFR status. A randomized, open-label, phase III study was performed at 12 institutions. Patients with failure of first-line platinum regimens were randomized to receive either single-agent sodium cantharivsdinate (SCA) or single-agent docetaxel (DOX) or docetaxel/sodium cantharidinate combination (CON). The primary endpoints were centrally confirmed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. A total of 148 patients were enrolled in our study between October 2016 and March 2020. After a median follow-up time of 8.02 months, no significant difference was observed among the three groups in ORR (SCA vs. DOX vs. CON: 6.00% vs. 8.33% vs. 10.00%, respectively; p=0.814) and DCR (74.00% vs. 52.00% vs. 62.50%, respectively; p=0.080). In additional, the mOS was significantly higher in the CON group, compared with the single-agent groups (7.27 vs. 5.03 vs. 9.83 months, respectively; p=0.035), while no significant differences were observed in terms of PFS (2.7 vs. 2.9 vs. 3.1 months, respectively; p=0.740). There was no significant difference in the baseline QoL scores between the three groups (p&gt;0.05); after treatment, life quality in SCA and CON group was significantly better than that in the DOX group (p&lt;0.05). Furthermore, the incidence of adverse events (AEs) in the SCA group was significantly lower (46.00 vs. 79.17 vs. 25.00%, respectively; p=0.038) and the incidence of grade ≥3 AEs was also significantly lower in the SCA group compared with the DOX and CON groups (10.00 vs. 82.00 vs. 30.00%, respectively; p=0.042). Single-agent SCA and single-agent DOX has similar therapeutic efficacy in the second-line treatment of advanced/metastatic NSCLC with wild-type or unknown EGFR status, but single-agent SCA has fewer AEs and better QoL. Also, SCA plus DOX can significantly improve OS and exerted a significant synergistic effect, with good safety and tolerance profile.

A randomized phase 2 trial of amrubicin compared to topotecan as second-line treatments in extensive disease small cell lung cancer (SCLC) sensitive to platinum-based first-line chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18064-18064
Author(s):  
R. M. Jotte ◽  
C. H. Reynolds ◽  
P. Conkling ◽  
J. W. Oliver ◽  
A. Allen
Keyword(s):  
Standard Therapy ◽  
Reference Group ◽  
Performance Status ◽  
Line Treatment ◽  
Second Line ◽  
Phase 2 ◽  
First Line ◽  
Open Label ◽  
Extensive Disease ◽  
Grade 3

18064 Background: SCLC accounts for about 13% of lung cancers and presents as extensive disease (ED-SCLC) in 60%-70% of patients (pts). Treatment options have been limited for ED-SCLC and survival enhanced by a median of only 2–3 months over the past 20 years. Our trial assessed response rates with amrubicin, a fully synthetic anthracycline and inhibitor of DNA topoisomerase II, versus standard therapy topotecan, for second-line treatment of sensitive SCLC. Methods: This phase 2, open-label, multicenter trial compares second-line therapy with amrubicin versus topotecan in ED-SCLC pts (=18 years, ECOG performance status =2), sensitive to first-line platinum-based therapy but with recurrence or progression =90 days later. Pts are randomized to amrubicin (40 mg/m2 via 5-minute bolus infusion daily x 3 days) or topotecan (1.5 mg/m2 via 30-minute infusion daily x 5 days), both starting on Day 1 of a 21 day cycle. Treatment is continued until disease progression, unacceptable toxicity, or withdrawal. Response is assessed using RECIST criteria. In all, 75 evaluable pts (50 randomized to amrubicin and 25 to topotecan; 2:1 per the standard topotecan therapy reference group) are planned to be enrolled. Results: To date, 22 pts are enrolled with 15 evaluable for response: 10 on amrubicin; 5 on topotecan. After 1–6 cycles, 5/10 amrubicin pts have responded (1 CR, 4 PRs). One topotecan patient responded (PR) but had progressive disease at the next visit. Seventeen pts are evaluable for safety. Hematological adverse events (AEs, = Grade 3) were the most commonly reported and were similarly observed across treatments (Table). Tachycardia (< Grade 3) was recorded for 1 amrubicin and 2 topotecan pts. No other cardiac AEs were observed. Conclusions: Amrubicin compares favorably with standard therapy topotecan as second-line treatment in sensitive ED-SCLC patients. No anthracycline- induced cardiomyopathy has been observed to date. [Table: see text] No significant financial relationships to disclose.

Surufatinib in combination with toripalimab in patients with advanced neuroendocrine carcinoma: Results from a multicenter, open-label, single-arm, phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16199-e16199
Author(s):  
Lin Shen ◽  
Xianjun Yu ◽  
Ming Lu ◽  
Xing Zhang ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Neuroendocrine Carcinoma ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Grade 3

e16199 Background: Patients with advanced neuroendocrine carcinoma (NEC) have a poor prognosis and limited treatment option after first-line treatment. Surufatinib, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1 and CSF-1R, has been approved in patients with advanced or metastatic extra-pancreatic neuroendocrine tumors in China. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Surufatinib modulates tumor immune microenvironment and has shown promising antitumor activity in combination with toripalimab in solid tumors, including neuroendocrine tumor and neuroendocrine carcinoma. Herein, we reported the efficacy and safety of surufatinib in combination with toripalimab in a cohort of advanced NEC patients. Methods: The multicenter, open-label, single-arm phase II clinical trial enrolled advanced NEC patients refractory to first-line chemotherapy, and received surufatinib 250 mg once a day orally plus toripalimab 240 mg intravenously on day 1 of a 21-day cycle. The primary end point is objective response rate (ORR) per RECIST 1.1. Results: Twenty-one patients enrolled and received combination therapy. At data cut-off (December 31, 2020), the average treatment cycles were 5.1±3.69 for surufatinib and 5.0±3.68 for toripalimab. Among 20 tumor evaluable patients, 4 patients achieved confirmed PR and 10 patients achieved stable disease. The ORR and disease control rate (DCR) are 20 % (95%CI: 5.7%-43.7%) and 70% (95%CI: 45.7%-88.1%) respectively. The median PFS is 3.94 months (95%CI: 1.31- unknown). OS is not mature till data cut-off. Adverse events (AEs) reported as related to treatment (TRAE) occurred in 100% of patients, of which Grade≥3 TRAEs occurred in 33.3% of patients. The reported Grade≥3 TRAEs were hypertension in 2 (9.5%) patients, and upper abdominal pain, oral mucositis, neutrophil count decreased, leukocyte count decreased, dermatitis, anemia and backache in 1 (4.8%) patient each. Immune related Grade ≥3 AEs, Gamma-glutamyl transpeptidase increased and dermatitis, occurred in 2 (9.5%) patients, respectively. TRAE caused surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious AEs nor AEs inducing treatment discontinuations or deaths. Conclusions: As there is no standard second-line treatment, this combination of surufatinib and toripalimab might offer a new promising choice to treat NEC as second-line treatment due to good efficacy and manageable treatment related toxicities. Clinical trial information: NCT04169672.

Bevacizumab continuation versus no continuation after first-line chemo-bevacizumab therapy in patients with metastatic colorectal cancer: A randomized phase III noninferiority trial (SAKK 41/06).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3503-3503 ◽  
Author(s):  
Dieter Koeberle ◽  
Daniel C. Betticher ◽  
Roger Von Moos ◽  
Daniel Dietrich ◽  
Peter Brauchli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Statistical Power ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Line Chemotherapy ◽  
First Line Treatment

3503 Background: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after stop of first-line chemotherapy. Methods: In an open-label, phase 3 multicenter study conducted in Switzerland, patients with unresectable metastatic colorectal cancer having non-progressive disease after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned in a 1:1 ratio to continuing bevacizumab (7.5 mg/kg every 3 weeks) or no treatment. CT scans were done every 6 weeks between randomization and disease progression. The primary endpoint was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significant level of 10% and a statistical power of 85%. Results: The per-protocol population comprised 262 patients. Median follow-up is 28.6 months (range, 0.6-54.9 months). Median TTP was 17.9 weeks (95% CI 13.3-23.4) for bevacizumab continuation and 12.6 weeks (95% CI 12.0-16.4) for no continuation; HR 0.72 (95% CI 0.56-0.92). Median progression free-survival and overall survival, both measured from start of first-line treatment, was 9.5 months and 24.9 months for bevacizumab continuation and 8.5 months (HR 0.73 (95% CI 0.57 - 0.94)) and 22.8 months (HR 0.87 (95% CI 0.64 – 1.18)) for no continuation. Median time from randomization to second-line treatment was 5.9 months for bevacizumab and 4.8 for no continuation. Grade 3-4 adverse events in the bevacizumab continuation arm were uncommon. Conclusions: Non-inferiority could not be demonstrated. The 95% confidence intervals for the TTP HR indicate superiority of bevacizumab continuation after stop of first-line chemotherapy. The median differences in TTP and in time between randomization and start of second-line treatment were of moderate magnitude being less than 6 weeks. The results of an accompanying cost analysis will be presented at the meeting. Clinical trial information: NCT00544700.

A phase III trial (ZJBIO009): CMAB009 plus irinotecan versus irinotecan alone as second-line treatment after fluoropyrimidine and oxaliplatin failure in wild-type K-ras metastatic colorectal cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3513-3513
Author(s):  
Yuankai Shi ◽  
Jin Li ◽  
Jianming Xu ◽  
Ying Cheng ◽  
Wei Liu ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Efficacy Evaluation ◽  
Open Label ◽  
Type K ◽  
Grade 3 ◽  
Colorectal Cancer Patients

3513 Background: More efficient second line treatment regimen for mCRC is urgently needed. CMAB009, a recombinant human/mouse chimeric monoclonal antibody, is specifically targeting human epidermal growth factor receptor. This study aimed to determine clinical efficacy and safety of CMAB009 plus irinotecan compared with irinotecan alone in wild-type K-ras mCRC patients (pts). Methods: This is a open-label, randomized, phase 3 trial. Patients had histologically confirmed wild-type K-ras mCRC, who previous failure of 5-fuorouracil plus oxaliplatin more than 1 month of the last-dose enrolled in study. Pts were randomly assigned on a 2:1 to receive CMAB009 (initial 400mg/m2 on day 1, and then 250 mg/m2 weekly) plus irinotecan (180mg/m2, every 2 weeks) (A arm) or irinotecan alone (B arm). B arm pts could switch to CMAB009 sequential treatment (C arm) on diseas progression. The primary end point was overall response rate (ORR). The secondary endpoints were PFS, OS, DCR, and DOR (NCT01550055). Results: From May 2009 to December 2012, 512 pts were assigned from 38 sites. Efficacy evaluation could be in 501 pts, ORR were 33.2% (112/337) and 12.8% (21/164) in A arm and B arm ( p <0.0001). C arm had 115 pts, DCR was 63.5% (73/115). DOR in A arm and B arm were 210 days and 109 days ( p=0.001). In C arm, DOR was 148 days . Median PFS was significantly longer in A arm than B arm (169 days vs 95 days; p < 0.0001). In C arm, median PFS was 84 days. Median OS was 425 days in A arm and 401 days in B arm ( p=0.94). 96.2% (484/503) pts experienced at least one adverse event (AE). 55.3%(187/338) and 37.6%(62/165) patients in A arm and B arm had at least one grade ≥3 AE respectively. The most common AE included diarrhea, emesis, leucopenia, neutropenia and fatigue. Adding CMAB009 to irinotecan increased the risk of rash (66.6% vs 5.5%, p <0.001) and paronychia (9.8% vs 0,p < 0.001). Conclusions: CMAB009 plus irinotecan significantly increased ORR and prolonged PFS compared with irinotecan alone. CMAB009 plus Irinotecan were efficient and well tolerated, which could be considered as a standard second-line treatment choice in wild-type K-ras mCRC pts. Clinical trial information: NCT01550055.

Randomized Phase II Trial of Single-Agent Amrubicin or Topotecan as Second-Line Treatment in Patients With Small-Cell Lung Cancer Sensitive to First-Line Platinum-Based Chemotherapy

2011 ◽  
Vol 29 (3) ◽  
pp. 287-293 ◽  
Author(s):  
Robert Jotte ◽  
Paul Conkling ◽  
Craig Reynolds ◽  
Matthew D. Galsky ◽  
Leonard Klein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Grade 3

Purpose This phase II study evaluated the safety and efficacy of single-agent amrubicin versus topotecan in patients with small-cell lung cancer (SCLC) sensitive to first-line platinum-based chemotherapy. Patients and Methods Patients were randomly assigned 2:1 to amrubicin (40 mg/m2/d in a 5-minute intravenous [IV] infusion, days 1 through 3, every 21 days) or topotecan (1.5 mg/m2/d in a 30-minute IV infusion, days 1 through 5, every 21 days). The primary efficacy end point was overall response rate (ORR) for amrubicin. Secondary end points included time to progression, median progression-free survival (PFS), and median overall survival (OS). Results Of 76 patients enrolled, 50 patients were randomly assigned to amrubicin, and 26 patients were randomly assigned to topotecan. Amrubicin treatment resulted in a significantly higher ORR than topotecan (44% v 15%; P = .021). Median PFS and median OS were 4.5 months and 9.2 months with amrubicin and 3.3 months and 7.6 months with topotecan, respectively. Tolerability was similar with both agents. However, grade 3 or worse neutropenia and thrombocytopenia seemed to be more frequent in the topotecan group as compared with the amrubicin group (78% and 61% v 61% and 39%, respectively). Conclusion Amrubicin shows promising activity, with an ORR of 44% compared with an ORR of 15% for topotecan as second-line treatment in patients with SCLC sensitive to first-line platinum-based chemotherapy. In addition, the safety profiles were comparable; however, a trend was noted for more frequent grade 3 or worse neutropenia and thrombocytopenia in the topotecan group as compared with the amrubicin group. Additional studies are ongoing.

Phase III randomized sequential open-label study to evaluate the efficacy and safety of sorafenib followed by pazopanib versus pazopanib followed by sorafenib in the treatment of advanced/metastatic renal cell carcinoma (SWITCH-2 study).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4591-TPS4591 ◽  
Author(s):  
Juergen Gschwend ◽  
Aart Beeker ◽  
Maria de Santis ◽  
Bernhard Brehmer ◽  
Matthias R. Zaiss ◽  
...  
Keyword(s):  
Treatment Time ◽  
Research Programme ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy

TPS4591 Background: Sorafenib (SO) and pazopanib (PA) are both effective treatments for metastatic RCC (mRCC). For optimal treatment of mRCC patients (pts) it is essential to compare efficacy and safety of different sequential 1st and 2nd line treatments. The primary endpoint of this study is to evaluate if total PFS of SO followed by PA is non-inferior to PA followed by SO. Secondary objectives include time to progression during second-line treatment; time to first-line treatment failure in each arm, and PFS in first- and second-line treatment; overall survival; disease control rate in first- and second-line, safety and tolerability, and health-related quality of life. Also, a comprehensive translational research programme is integrated. Methods: Major inclusion criteria: pts with metastatic/advanced RCC not suitable for cytokines and for whom study medication constitutes first-line therapy; 18-85 years, ECOG PS 0 or 1, MSKCC score low or intermediate; at least one measurable lesion (RECIST 1.1). 544 pts will be randomized to the sequence SO→PA or PA→SO. Treatment under each drug continues until progression or intolerable toxicity. Between 1st and 2ndline therapy will be a treatment-free period of 1-4 wks. SO and PA are given in their registered doses. Pts undergo CT/MRI after every second cycle, i.e. after every 8 wks. The experimental arm will be considered to be non-inferior as long as the lower limit of the HR 95 % confidence interval (one-sided) excludes a median total PFS lower than 13.1 mos (=non inferiority margin). 383 events need to be observed to have 80% power to reject the null hypothesis of inferiority (HR ≥1.225) when the true HR=0.95. Recruitment started in June 2012. Study centers are in Germany, The Netherlands, and Austria. Clinical trial information: NCT01613846.

A phase I/II study of RX-3117, an oral antimetabolite nucleoside, in combination with nab-paclitaxel (nab-pac) as first-line treatment of metastatic pancreatic cancer (met-PC): Preliminary results.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 420-420
Author(s):  
Hani M. Babiker ◽  
Peter J. Schlegel ◽  
Lee G. Hicks ◽  
Andrea J. Bullock ◽  
Nafisa Burhani ◽  
...  
Keyword(s):  
Clinical Study ◽  
Phase I ◽  
Phase Ii ◽  
Single Agent ◽  
Complete Response ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
First Line Treatment

420 Background: RX-3117 is an oral small molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by cancer-enriched uridine cytidine kinase 2. Single agent RX-3117 has demonstrated efficacy in a phase III single agent clinical study of RX-3117 in met-PC and bladder cancer. RX-3117 in combination with nab-pac is being evaluated as first line treatment of met-PC cancer. Methods: This is a multicenter, open label phase I/II study (NCT03189914). Eligible subjects (aged ≥ 18 years) have histologically or radiologically proven met-PC with no prior therapies for metastatic disease, ECOG PS 0-1, and normal lab values. phase I identified the MTD dose that is being further evaluated in the phase II: RX-3117 (700 mg administered orally once-daily for 5 consecutive days with 2 days off per week) and nab-pac (125 mg/m2 administered once weekly) for 3 weeks with 1 week off per 4-week cycle. The Safety Committee reviewed data from phase I before moving to phase II. The primary endpoint of phase II (dose expansion) is an adequate number of responders based on PFS at 4 months and/or objective clinical response per RECIST v1.1. Results: As of September 21, 2018, 8 phase I subjects and 13 phase II subjects were enrolled and treated (9 males and 12 females, median age 67 years). The most common (≥ 15%) related adverse events were nausea, diarrhea, fatigue, alopecia, decreased appetite, rash, vomiting, and anemia. Fourteen subjects had at least one on-study scan (after 2 cycles). One subject experienced a complete response (CR) after 6 cycles of therapy with normalization of CA19.9 (-76%). Three subjects exhibited a partial response (PR): two after 2 cycles (39-47%) and one after 4 cycles of therapy (36%). Eight subjects had stable disease for at least 2 months, and 4 subjects had PFS of at least 4 months. The disease control rate (CR+PR+SD) was 86% in evaluable subjects while the overall response rate (CR+PR) was 29%. Conclusions: RX-3117 in combination with nab-pac appears to be safe and well tolerated in subjects with met-PC. Antitumor activity per RECIST was observed in 12 subjects. Phase II of the clinical study is currently ongoing. Clinical trial information: NCT03189914.

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