Activity of RX-3117, an oral antimetabolite nucleoside, in patients with pancreatic cancer: Preliminary results of stage 1 of the phase 1a/2b.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 445-445 ◽  
Author(s):  
Drew W. Rasco ◽  
Christine Peterson ◽  
Ely Benaim ◽  
Jaime R. Merchan
Keyword(s):  
Pancreatic Cancer ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Cancer Data ◽  
Phase 1B ◽  
Stage 1

445 Background: RX-3117 is an oral smallmolecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 1 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 1 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle in a 2-stage Simon design. Eligible subjects (aged ≥ 18 years) were those with relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% (2 out of 10 subjects) rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% (1 of 10 subjects) with a partial response rate or better. Results: As of Sep 2016, 8 out of 10 subjects have been enrolled (4 females, 4 males), the mean age was 70 years, ECOG performance status was 1 and 5 subjects had received more than 4 prior therapies. Two subjects met the primary endpoint of stable disease with a duration of 140-168 days at the time of this submission. The most frequent adverse events were moderate to severe anemia, mild to moderate fatigue, abdominal pain and diarrhea. Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. As the primary endpoint has been achieved, the study will now move to stage 2 where an additional 40 subjects with advanced pancreatic cancer will be enrolled. Clinical trial information: NCT02030067.

RX 3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancer–Preliminary results of stage II of the phase Ia/IIb study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 396-396
Author(s):  
Vincent M. Chung ◽  
Jaime R. Merchan ◽  
Allyson J. Ocean ◽  
Drew W. Rasco ◽  
Hani M. Babiker ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Partial Response ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Cancer Data ◽  
Phase 1B

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 2 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% of evaluable subjects with a partial response rate or better. Results: As of Sep 2017, 44 subjects have been enrolled (22 females, 22 males). The median age was 68 years, ECOG performance statuses were 0 (13 subjects) and 1 (31 subjects) and 6 subjects had received 4 or more prior therapies. One subject had an unconfirmed partial response and 21 subjects met the primary endpoint of stable disease with a duration of 30-224 days. The most frequent adverse events were mild to moderate anemia (19%), mild to moderate fatigue (15%), mild to moderate diarrhea (11%), and severe anemia (9%). Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started. Clinical trial information: NCT02030067.

Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group

2007 ◽  
Vol 25 (16) ◽  
pp. 2212-2217 ◽  
Author(s):  
Richard Herrmann ◽  
György Bodoky ◽  
Thomas Ruhstaller ◽  
Bengt Glimelius ◽  
Emilio Bajetta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Karnofsky Performance Score ◽  
Phase Iii Trial ◽  
Good Performance Status ◽  
Grade 3

PurposeThis phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2twice daily on days 1 to 14 plus Gem 1,000 mg/m2by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent.ResultsA total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms.ConclusionGemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for patients with advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16257-e16257
Author(s):  
Huayun Zhu ◽  
Xiaofeng Sun ◽  
Xuan Pan ◽  
Pingping Wu ◽  
Jia Chen
Keyword(s):  
Pancreatic Cancer ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Combined Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

e16257 Background: This study aimed to evaluate the efficacy and safety of Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for advanced pancreatic cancer. Methods: This was a single-arm, simple-center, exploratory trial, which included advanced pancreatic cancer pts. Patients received Sindilimab combined with nab-paclitaxel plus gemcitabine. Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take Sindilimab as single agent until disease progression or intolerable toxicity. Response was assessed every 8 weeks. Results: 16 eligible patients were enrolled and 14 pts were evaluable for efficacy analysis. Baseline characteristics are shown in Table 2. Conclusions: This study has showed high anti-tumor efficacy and tolerant toxicity in first-line regimen for advanced pancreatic cancer. Furthermore, it is needed to be proved in update results and large scale studies. Efficacy As shown in Table 3, among 14 evaluable pts, unconfirmed ORR was 57.1% and DCR was 92.8%. 8 pts got partial response (PR), 5 pts stable disease (SD) and 1 pts progressive disease(PD) at best. PFS: The primary endpoint 6-month PFS rate was 2%(95% CI 50.4%-72.4%). Which indicated that the primary endpoint of the study was reached. And mPFS was 7.3 months(95% CI 5.9-8.1). OS: Median OS was not reached and 6m-OS rate was 85.7% (95%CI 5%-91.3%). Safety. All 16 pts were included in the safety analysis (Table 4). The overall AE incidence rate was 93.75% .≥Grade 3 irAE included GGT increased (37.5%) and peripheral neuropathy (6.25%). No TRAE led to death.[Table: see text][Table: see text][Table: see text][Table: see text]

A phase II study of S-1 in gemcitabine-refractory metastatic pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4115-4115 ◽  
Author(s):  
C. Morizane ◽  
T. Okusaka ◽  
J. Furuse ◽  
H. Ishii ◽  
H. Ueno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Primary Study ◽  
Standard Regimen

4115 Background: Gemcitabine (Gem) monotherapy or Gem-containing chemotherapy is the standard first line therapy for advanced pancreatic cancer. After disease progression, there is no standard regimen available. In a previous phase II trial (J. Furuse et al, Proc ASCO 2005: # 4104), S-1 has been reported to show considerable efficacy, achieving a response rate of 37.5% in chemo-naïve patients with pancreatic cancer. This study evaluated the efficacy and toxicity of S-1 in patients with Gem-refractory metastatic pancreatic cancer. Methods: Eligibility criteria were pathologically-proven pancreatic cancer with confirmation of progressive disease while receiving Gem-based chemotherapy, Karnofsky performance status 80 to 100%, age 20 to 74 years, with measurable metastatic lesions, adequate hematological, renal and liver functions, and written informed consent. S-1 was administered orally at 40 mg/m2 twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. The primary study end point was objective response, secondary end points included toxicity, progression-free survival (PFS) and overall survival, as well as clinical benefit response in symptomatic patients. Results: Forty patients (pts) from two institutions were enrolled between September 2004 and November 2005. Thirty-three pts are currently evaluable for response in this ongoing trial. There have been 5 confirmed partial responses (12.5%), and 14 pts (35%) with stable disease. Median survival has not been reached. Median PFS was 2.1 months. Toxicity data were available for 28 patients. Grade 3 and 4 toxicities were anemia (1 pts), appetite loss (2 pts), and fatigue (2 pts). Conclusions: Preliminary results demonstrated the safety and activity of S-1 in Gem-refractory metastatic pancreatic cancer. Efficacy and toxicity analysis are ongoing. Final results will be presented at the meeting. No significant financial relationships to disclose.

Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15111-15111 ◽  
Author(s):  
Y. Park ◽  
S. Yi ◽  
H. Kim ◽  
S. Lee ◽  
I. Hwang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

Updated results of the GEST study: Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer in Japan and Taiwan.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4035-4035 ◽  
Author(s):  
Akira Fukutomi ◽  
Takuji Okusaka ◽  
Kazuya Sugimori ◽  
Hideki Ueno ◽  
Tatsuya Ioka ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Primary Endpoint ◽  
Advanced Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Locally Advanced Disease ◽  
Phase Iii Study

4035 Background: The GEST study (Ioka et al. ASCO 2011, Abstract 4007) demonstrated the non-inferiority of S-1 to GEM with respect to the primary endpoint of overall survival (OS) in patients with pancreatic cancer (PC). We now report the updated results of this study. Methods: The GEST study was a randomized, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG Performance status (PS) of 0-1, and adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w), or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was OS, used to assess the non-inferiority of S-1 and the superiority of GS to GEM. Patient information was updated in July 2011. Results: At the time of this follow-up analysis, median follow-up was 29.8 months with 795 OS events, compared with 18.4 months with 710 OS events out of 832 patients at the previous analysis. Median OS was 8.8 months (95% CI: 8.0–9.7) in the GEM group and 9.7 months (95% CI: 7.6-10.8) in the S-1 group (HR=0.96, 97.5% CI: 0.79-1.17, p<0.001 for non-inferiority), which is consistent with prior results (HR=0.96, 97.5% CI: 0.78-1.18, p<0.001). In the GS group, median OS was 9.9 months (95% CI: 9.0-11.2). The HR was 0.91 (97.5%CI: 0.75-1.11, p=0.28 for superiority versus the GEM group). On subgroup analysis, GS was associated with a non-statistically significant trend toward better OS compared with GEM among patients with locally advanced disease and those with a PS of 1. Median OS was 12.7 months (95% CI: 9.7–14.9) in the GEM group and 15.9 months (95% CI: 13.0-19.7) in the GS group (HR=0.72, 95% CI: 0.51-1.03) among patients with locally advanced disease, and 6.2 months (95% CI: 4.9–8.3) in the GEM group and 9.6 months (95% CI: 8.0-10.9) in the GS group (HR=0.62, 95% CI: 0.46-0.83) among patients with a PS of 1. Conclusions: The non-inferiority of S-1 to Gem in terms of the primary endpoint of OS was reconfirmed. Monotherapy with S-1 can be used as one of the standard treatments for advanced PC. As for GS therapy, there is room for further investigation.

Use of the Optimata Virtual Patient (OVP) to predict effects of sunitinib malate in advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 341-341
Author(s):  
M. Kleiman ◽  
S. Shacham ◽  
M. Kushnir ◽  
E. Chapnik ◽  
Z. Agur
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Patient Population ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Growth Patterns ◽  
Treatment Modalities ◽  
Large Set ◽  
Sunitinib Malate

341 Background: Pancreatic cancer is considered to be incurable by available treatment modalities, with 5-year survival rate <4%. Sunitinib malate (Sutent) significantly increased progression-free survival in patients with advanced islet cell tumors (pancreatic); however, it demonstrated only modest single-agent effect in a phase II study in patients with metastatic pancreatic adenocarcinoma (PaC) that progressed after first-line therapy with gemcitabine. To improve the response of PaC patients to drugs, the interplay between biologic, pathologic, and pharmacologic processes underlying drug-patient interactions have been mathematically modeled, predicting efficacy responses, different toxicities, and long-term tolerability in clinical trials, allowing for improved dosing regimens and patient selection (OVP engine) (Agur Z., 2010). The OVP engine was used to predict Sunitinib malate single-agent activity in advanced PaC. Methods: OVP replicated the observed growth patterns of human PaC. Pharmacokinetics (PK) and pharmacodynamics (PD) of sunitinib malate were modeled based on literature (NDA 21-938). Effects of sunitinib malate on human PaC xenografts were scaled to model PK/PD in human. To evaluate drug efficacy in advanced PaC patient-population, a Virtual PaC Patient- Population was created by replacing the population averaged parameter values in the model by their distribution in the population. Using this procedure, a large set of virtual patients was generated. Model simulations with sunitinib malate therapy (50 mg QD/28 days; 14 days rest [1 cycle]) enabled the prediction and classification of patients' response according to RECIST criteria and compared with the actual clinical response (O'Reilly et al, 2008). Results: Simulations of the FDA-approved schedule, predicted a stable disease in 81% of the patients following one treatment cycle and 54% following two treatment cycles. Stable disease was predicted to be the best observed response, which was confirmed in the clinical study. Conclusions: Our model predictions are compatible with clinical results of a recent phase II trial with the same treatment regimen of sunitinib malate (O'Reilly et al, 2008) and further suggest the use of mathematical model during drug development. [Table: see text]

Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14614-e14614 ◽  
Author(s):  
Hemchandra Mahaseth ◽  
John S. Kauh ◽  
Edith Brutcher ◽  
Natalyn Nicole Hawk ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Emory University ◽  
Grade 3

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m2 CIVI over 46 hours, leucovorin 400 mg/m2, oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.

A phase Ib trial of IPI-926, a hedgehog pathway inhibitor, plus gemcitabine in patients with metastatic pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 213-213 ◽  
Author(s):  
Donald Anthony Richards ◽  
Joe Stephenson ◽  
Brian M. Wolpin ◽  
Carlos Becerra ◽  
John Turner Hamm ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Final Report ◽  
Double Blind ◽  
Free Survival ◽  
Phase 1B ◽  
Grade 3 ◽  
Dose Reductions

213 Background: IPI-926 is a novel, natural product-derived small molecule that targets the Hedgehog (Hh) pathway by inhibiting smoothened. In preclinical models of pancreatic cancer, repressing activation of the Hh pathway diminishes tumor-associated desmoplasia and improves chemotherapy delivery. Methods: This is the final report of the Phase 1b portion of a Phase 1b/2 trial evaluating the safety and efficacy of IPI-926 plus gemcitabine. Eligible patients (pts) with untreated metastatic pancreatic cancer and ECOG status 0-1 were administered oral IPI-926 daily (QD) for 28-day cycles, in 3 to 6 pt dose cohorts. Gemcitabine (1,000 mg/m2) was administered IV weekly for 3 weeks with 1 week off. DLTs were evaluated during Cycle 1. Results: 16 pts (median age 69 years; range 58-86) were enrolled at IPI-926 doses of 110, 130 or 160 mg QD (single agent MTD). Pts received a median of 5 cycles (1-13). Two pts remain on trial. No IPI-926-related serious AEs have been observed. One DLT of Grade 3 AST increase was observed (130 mg dose cohort) and was asymptomatic; it resolved with dose interruption, and did not recur with dose reduction. The most common AEs occurring were fatigue (75% total, 6% ≥ Grade 3), thrombocytopenia (63%, 25%), anemia (56%, 13%), nausea (50%, 0%), diarrhea (44%, 0%), vomiting (44%, 0%), peripheral edema (44%, 0%), pyrexia (44%, 0%), and AST increase (44%, 13%). Dose reductions of IPI-926 occurred in 3 (19%) pts. Dose reductions of gemcitabine occurred in 11 (69%) pts, primarily for thrombocytopenia (9 pts). One pt (6%) discontinued due to an AE (microangiopathic hemolytic anemia). Five (31%) radiographic partial responses were observed (1/3 at 110 mg, 2/6 at 130 mg, 2/7 at 160 mg). Median progression-free survival is > 7 months. 74% of pts were alive 6 months after study entry. Conclusions: IPI-926 plus gemcitabine is well tolerated in pts with untreated metastatic pancreatic cancer, with evidence of activity and no unexpected toxicity. Complete Phase 1b data, including final overall survival, will be presented. Clinical evaluation of this combination continues in the randomized, double-blind, placebo-controlled Phase 2 portion of the trial.

A phase II trial of capecitabine and docetaxel in patients with previously treated pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14111-14111
Author(s):  
G. Lopes ◽  
B. Bastos ◽  
E. Ahn ◽  
J. A. Quesada ◽  
M. Allison ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Sequential Design ◽  
Ca 19.9 ◽  
Ecog Ps

14111 Background: There is no accepted standard treatment for patients with advanced pancreatic cancer who progress after gemcitabine-based therapy. Capecitabine and docetaxel have single-agent activity in pancreatic cancer and have documented synergy in both pre-clinical models and in the treatment of other solid tumors. Methods: A phase II trial with a 3-stage sequential design was planned to assess the efficacy (primary end-point: response rate) and toxicity of capecitabine 800 mg/m2 PO bid on days 1–14 in combination with docetaxel 30 mg/m2 IV on days 1 and 8 of each 21-day cycle in patients with advanced pancreatic cancer who failed first-line gemcitabine-based chemotherapy. If no responses are observed after 13 patients or less than 3 responses are seen after 26 patients, accrual will stop and the combination deemed ineffective. Results: Eight patients have been enrolled (5 women, 3 men). Median age was 67 years. ECOG PS was as follows: PS 1, three patients; PS 2, five patients. All patients had adequate organ function. A total of 26 cycles have been administered (median: 2 cycles, range 1 to 8). Four patients had stable disease (median duration 9 weeks, range 6 to 24), and 3 had progressed at the time of first evaluation (2 cycles). One patient has not yet completed 2 cycles and is therefore not assessable for radiologic response. Out of 7 patients with an elevated CA 19–9, four had a decrease of 50% or greater while on chemotherapy. Grade 1 or 2 toxicity was seen in 3 patients (diarrhea, 1 patient; fatigue, 2 patients). Grade 3 or 4 toxicity was as follows: fatigue, 2 patients; dehydration, 1 patient; neuropathy, 1 patient. There were no treatment related deaths. Enrollment continues. Efficacy data fulfilling the first stage sequential design should be available at the time of the meeting. Median survival for all patients is currently 13 weeks (range 7–23 weeks) Conclusions: Capecitabine in combination with docetaxel is a well-tolerated regimen in the treatment of patients with pancreatic cancer who have failed prior gemcitabine-based therapy. Four out of 8 patients have had stable disease. Four of 7 patients have had a decrease of 50% or greater in CA 19.9 levels. Enrollment continues. Median survival of 13 weeks underscores the poor prognosis of this patient population. [Table: see text]

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