Phase I/II trial of gemcitabine (Gem) plus irinotecan (CPT-11) for metastatic pancreatic cancer (MPC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 301-301
Author(s):  
Takuo Yamai ◽  
Tatsuya Ioka ◽  
Hironari Sueyoshi ◽  
Ryoji Takada ◽  
Nobuyasu Fukutake ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Phase I ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase I Study ◽  
Progressive Disease ◽  
Metastatic Pancreatic Cancer ◽  
Refractory Ascites ◽  
Recommended Phase Ii Dose

301 Background: Treatment options for patients with metastatic pancreatic cancer are still limited. Recently, new strategies to prolong disease control are reported. We conducted phase I/II trial of GEM+CPT-11 combination chemotherapy for MPC to evaluate the effectiveness and safety. Methods: As phase I study, traditional 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose. Four escalating dose levels of GEM/CPT-11 (800/60 mg/m2, 1000/60 mg/m2, 1000/80 mg/m2, and 1000/100 mg/m2) were studied. As results of this investigation, the recommended phase II dose was GEM 1000 mg/m2 and CPT-11 100 mg/m2, biweekly. Phase II eligibility included naïve MPC, PS0-2, Pathological diagnosis, no refractory ascites and pleural effusion, and adequate organ function. Primary endpoint was overall survival. Results: Eighteen patients were entered phase I study. The DLTs were anorexia, and nausea/vomiting. Severe neutropenia was rare. MTDs were determined GEM 1000 and CPT-11 100 mg/m2. After that, we investigated phase II trial in 40 patients. There were 6 partial response, 14 stable disease, 18 progressive disease and 2 in-evaluable. Response rate was 16%. The median overall survival was 7.5 months; progressive disease 4.0 months. Grade 3 to 4 toxicity included neutropenia (7%), anemia (7%), diarrhea (7%), ALT elevation (10%), pneumonitis(7%). There was no treatment-related death. Conclusions: This combination chemotherapy is not effective as first-line chemotherapy for metastatic pancreatic cancer. But this is safe and generally well tolerated. This chemotherapy could be effective of salvage chemotherapy with low toxicity after standard chemotherapy such as FOLFIRINOX.

A phase II multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15129-15129
Author(s):  
S. Ohkawa ◽  
A. Amano ◽  
M. Ueno ◽  
K. Miyakawa ◽  
K. Sugimori ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Survival Time ◽  
Median Survival ◽  
Phase Ii ◽  
Median Survival Time ◽  
Progressive Disease ◽  
Advanced Pancreatic Cancer ◽  
Combined Chemotherapy ◽  
Standard Drug

15129 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 trial and reported the results of the phase I trial last year. And this phase II study evaluated the efficacy and feasibility. Methods: The subjects had unresectable pancreatic ductal cancer. Eligibility criteria were pathologically-proven, Karnofsky performance status 80 to 100%, age 20 to 74 years, adequate hematological, renal, and liver functions and written informed consent. The method of administration was single administration of GEM on the first day of the week 1000 mg/m2, with concurrent administration of S-1 at 80 (<1.5 m2) to 100 (=1.5 m2) mg/day × 7 days, repeated every other week until the progressive disease or life threatening adverse events. This administration dose was determined from the result of the phase I study. The primary endpoint was median survival time. And the secondary endpoints were the overall response rate and the toxicities. Results: 40 patients(pts) were enrolled. Average age was 62.9±8.3 years (34–73 years). Thirty nine pts were conducted this therapy except one who refused this study before the start of administration. Thirty eight pts were evaluable for response, partial response, stable disease, progressive disease were observed in 7 (17.5%), 21 (52.5%) and 10 pts (25.0%), respectively. The median survival time at this stage is 276±51 days in this ongoing study. Grade 3 and 4 toxicities were mainly leucocytes(10 pts), neutrophils(8 pts) and anorexia(6 pts). Conclusions: The GEM plus S-1 combined chemotherapy is effective and feasible in patients with advanced pancreatic cancer. No significant financial relationships to disclose.

Emerging concepts in combination chemotherapy for metastatic pancreatic cancer: A systematic review of randomized controlled trials.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 228-228
Author(s):  
Basile M. Njei ◽  
Ivo C. Ditah ◽  
Alexei Shimanovsky ◽  
Priscilla Owusu ◽  
John W Birk
Keyword(s):  
Quality Of Life ◽  
Pancreatic Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Adverse Events ◽  
Combination Chemotherapy ◽  
Metastatic Pancreatic Cancer ◽  
Controlled Trials ◽  
Randomized Controlled

228 Background: Even though gemcitabine monotherapy is commonly used as first-line treatment for metastatic pancreatic cancer, many novel treatment approaches have focused on combination chemotherapy. FOLFIRINOX, a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin, has recently been shown to improve survival compared to gemcitabine. However, it is unclear whether survival benefits are counterbalanced by a poor quality of life due to the adverse effects. The aim of this study was to review emerging strategies that enhance treatment of patients with metastatic pancreatic cancer. Methods: Two authors independently conducted a comprehensive search of the Cochrane library PUBMED, and published proceedings from major oncologic and gastrointestinal cancer meetings from January 1980 to July 2012. Only published randomized controlled trials were eligible for inclusion. Our primary outcome measures were: progression-free survival (PFS), overall survival (OS) and serious adverse events (grade 3 or 4). Results: Thirty-one studies involving 7,957 patients were included in the analysis. There was an overall statistically significant increase in OS (RR 1.10, 95% CI 1.03-1.30) and PFS (RR 1.27, 95% CI 1.14-1.46) for the gemcitabine-based combination therapy group versus the gemcitabine monotherapy group. Subgroup analysis showed that only patients with fluoropyrimidine and platinum containing regimens showed prolonged survival: RR 1.33, 95% CI 1.04-1.76 and RR 1.38, 95% CI 1.08-1.76, respectively. The most common severe adverse event (neutropenia) was found in 45% of patients treated with FOLFIRINOX. Conclusions: Overall, gemcitabine in combination with fluoropyrimidine or platinum containing regimens can improve overall survival in patients with metastatic pancreatic cancer compared to gemcitabine alone. Even though, FOLFIRINOX therapy is associated with better survival outcomes than gemcitabine, the prolonged survival comes at the cost of poorer quality of life due to a higher incidence of adverse events. More data is needed from studies involving novel combination therapy such as hedgehog pathway inhibitors and radio-immunotherapy.

Phase I/II docetaxel, oxaliplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 162-162
Author(s):  
Sung Rok Kim ◽  
Sung-En Park ◽  
Young Jin Yuh ◽  
Byeong Seok Sohn ◽  
Hye Ran Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

162 Background: The results of recent studies with duo- or triple regimen for the advanced gastric cancer are still not satisfactory and the optimal doses of combinations with taxanes, fluorouracil and platinum analogues were not determined yet. The aim of this study is to determine the optimal dose of docetaxel and oxaliplatin in combination with 5-fluorouracil(FU) [DOF], with the efficacy and toxicity in patients (pts) with advanced gastric cancer. Methods: The pts with unresectable, metastatic, or relapsed gastric cancer were enrolled for a phase I/II study. The dose of docetaxel and oxliplatin was escalated from 50 mg/m2 and 80 mg/m2 day 1, respectively by traditional 3+3 design, and 5-FU was fixed at 850 mg/m2/day 24 hour continuous infusion day 1-4, all every 3 weeks. All pts had measurable disease and were assessable for toxicity. Results: A total of 50 pts including 12 patients from phase I study were enrolled. The recommended phase II dose of docetaxel and oxaliplatin were 60mg/m2 and 100mg/m2 on day 1 (cohort 2), respectively. A total of 335 cycles of chemotherapy was administrated (median: 6, range 1–24) and the dose intensity of docetaxel, oxaliplatin, and 5-FU were 96.3%, 96.2% and 98.5%, respectively. Twenty two (44.0%) of 50 patients showed partial response, 22 (44.0%) stable disease, and 1 (2.0%) complete response. The overall response rate was 46.0% (95% confidence interval [CI]: 32.2–60.0%) and the disease control rate 90.0% (95% CI: 81.7–98.3%). The median progression free survival was 6.5 months (95% CI, 3.3–9.8) and the overall survival 10.7 month (95% CI, 7.0–14.3). Grade 3/4 neutropenia and thrombocytopenia occurred in 81 (24.1%) and 3 cycles (0.9%), respectively [27 (56%) and 3 (6%) in 50 pts, respectively]. Grade 3/4 stomatitis, diarrhea and neuropathy occurred in 2 (0.6%), 6 (1.8%) and 6 cycles (5.7%), respectively. Conclusions: The recommended phase II dose of docetaxel and oxaliplatin was 60mg/m2 and 100mg/m2, respectively. This DOF combination chemotherapy has no better efficacy than reference regimen. The toxicities were substantial in some pts, but generally manageable.

GA CPI 613: A single arm, open-label phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel for patients with locally advanced or metastatic pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS459-TPS459
Author(s):  
Angela Tatiana Alistar ◽  
Bonny Morris ◽  
Lawrence Harrison ◽  
Kai Bickenbach ◽  
Nancy Ginder ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Locally Advanced ◽  
Glutamine Metabolism ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
First Line ◽  
Open Label ◽  
Effective Treatments

TPS459 Background: Pancreatic cancer is the third leading cause of cancer death in the USA. The most effective treatments for first-line metastatic pancreatic cancer are FOLFIRINOX and gemcitabine plus nab-paclitaxel, which provide a median overall survival of 11·1 months and 8·5 months with moderate toxicity. Safer and more effective treatments are needed. The glycolic and mitochondrial metabolism are aberrant in pancreatic cancer and translate into chemoresistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species such as Nab-Paclitaxel. CPI- 613 is a novel antimitocondrial developed by Rafael Pharmaceuticals that showed preclinical activity in pancreatic cancer cell lines as well as promising clinical activity in combination with modified FOLFIRINOX in patients with stage IV pancreatic cancer. Preclinical data suggests possible synergy of CPI- 613 with nab-paclitaxel. Methods: This is a single arm, open-label, nonblinded phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel in patients with locally advanced or metastatic pancreatic cancer. Key eligibility criteria include: histologically or cytologically documented and measurable locally advanced or metastatic pancreatic adenocarcinoma, ECOG performance status 0-2, first line treatment for both locally advanced or metastatic. CPI-613 will be infused intravenously with a starting dose of 500 mg/m2 followed by 125 mg/m2 nab-paclitaxel and 1,000 mg/m2 gemcitabine on day 1, 8, 15 of a 28-day cycle. The study is comprised of a two-stage dose-escalation schema to evaluate the MTD of CPI-613. At least six months of treatment is planned for patients who have a response. Primary endpoint of the study is MTD of CPI 613 when combined with gemcitabine and nab-paclitaxel and secondary endpoints of the study are treatment related adverse events, CR and PR. This study was initiated in February 2018 at Atlantic Health System and within first seven months of the study, 11 out of 24 planned patients have been enrolled. Clinical trial information: NCT03435289.

A Phase I Study of Combination Chemotherapy with Gemcitabine and Oral S-1 for Advanced Pancreatic Cancer

Oncology ◽  
2005 ◽  
Vol 69 (5) ◽  
pp. 421-427 ◽  
Author(s):  
Hideki Ueno ◽  
Takuji Okusaka ◽  
Masafumi Ikeda ◽  
Yoriko Ishiguro ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Combination Chemotherapy ◽  
Phase I Study ◽  
Advanced Pancreatic Cancer

A phase I study of axitinib (AG-013736), a potent inhibitor of VEGFRs, in combination with gemcitabine (GEM) in patients (pts) with advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13092-13092 ◽  
Author(s):  
J. Spano ◽  
M. Moore ◽  
S. Kim ◽  
K. F. Liau ◽  
B. Hee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Tyrosine Kinases ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Epigastric Pain ◽  
Cell Cancer ◽  
Advanced Pancreatic Cancer

13092 Background: Axitinib (AG-013736) is a novel small molecule inhibitor of the receptor tyrosine kinases with picomolar potency against VEGFR 1, 2 & 3 and nanomolar potency against PDGFR-beta and KIT. A phase I study in solid tumors identified 5 mg BID as the therapeutic dose; a phase II study in renal cell cancer demonstrated significant efficacy with a response rate (RR) of 46% (Rini et al, ASCO 2005). This study examined the safety, PK and preliminary efficacy of AG-013736 (AG) in combination with gemcitabine (GEM) as first-line therapy for advanced pancreatic cancer. Methods: A randomized phase II study was preceded by a phase I component. All patients (pts) in the phase I portion received 1000 mg/m2 GEM by 30-minute infusion on days 1, 8, and 15 followed by one week of rest from treatment. AG 5 mg p.o. BID was given beginning Cycle 1, Day 3 (C1D3). Eligible pts had no prior chemotherapy for advanced disease, ECOG 0–2, and no previous treatment with VEGF/VEGFR inhibitors, or anti-angiogenesis treatment. Full PK profiles were collected on C1D1 (GEM alone), C1D14 (steady state, AG alone), and C1D15 (GEM + AG). In the phase II trial, pts are randomized to AG or AG plus GEM beginning C1D1. Results: 8 pts were treated on the phase I portion of this trial. Toxicity: The primary Gr. 3/4 toxicity was hematologic: Gr. 4 anemia and Gr.3 thrombocytopenia in 1 pt and Gr. 3 neutropenia in 1 pt requiring a dose reduction for GEM in Cycle 3. Gr. 2 non-hematologic adverse events include pruritus (1 pt), abdominal pain (2 pts), epigastric pain (1 pt), melena (1 pt), and asthenia (2 pts). Gr. 2 hypertension was observed in 3 pts. Efficacy: Radiological assessment suggests 2 pts with partial response and 4 pts with stable disease: response assessments are ongoing. The median number of cycles is 3 [1,6]. Treatment for 4 pts is still ongoing: Cycle 6 (2 pts) and Cycle 2 (2 pts). Conclusions: This combination is safe and appears to be an effective treatment for advanced pancreatic cancer with significant tumor regression observed in 2 pts. Therapy was well tolerated with manageable toxicity. Additional investigation of AG-013736 in combination with GEM in the phase II setting for advanced pancreatic cancer is warranted. [Table: see text]

Clinical and immune responses using anti-CD3 x anti-EGFR bispecific antibody armed T cells (BATs) for locally advanced or metastatic pancreatic cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4135-4135 ◽  
Author(s):  
Lawrence G. Lum ◽  
Tri Minh Le ◽  
Minsig Choi ◽  
Archana Thakur ◽  
Matthew Reilley ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Phase I ◽  
Phase Ii ◽  
Bispecific Antibody ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Cytotoxic T Cell ◽  
Ifn Γ

4135 Background: Conventional chemotherapy (chemo) for locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC) has dismal responses and poor survival rates. Arming activated T cells (ATC) with anti-CD3 x anti-EGFR bispecific antibody (BATs) makes every ATC into an EGFR-specific cytotoxic T cell that secretes cytokines, proliferates, and kills tumor. Methods: We report on 5 phase I (P1) and 15 phase II (P2) patients. In our phase I study, BATs were used to treat LAPC or MPC patients at Karmanos Cancer Institute (NCT0140874) in a dose escalation involving 3 weekly infusions of 1, 2, and 4 x 1010 BATs/infusion, followed by a booster infusion at 3 months (mos) for a total of up to 8 x 1010 BATs. No dose limiting toxicities were observed in the outpatient infusions. Fifteen patients treated on a phase II (NCT02620865) at KCI and (NCT03269526) at University of Virginia received biweekly infusions of 1010 BATs/infusion over 4 weeks for a total of 8 x 1010 EGFR BATs. Results: Four patients had stable disease (SD) for 6.1, 6.5, 5.3, and 36 mos. Two patients had complete responses (CR) when chemo was restarted after BATs. The median overall survival (OS) for 17 evaluable patients (3 of 4 infusions in the P1 and all 8 infusions in the P2) was 31 mos, and the median OS for all 20 patients (3 in the P2 who did not complete 8 infusions) is 14.5 mos (95% CI, 7.5-45.2 mos). Patient IT20104 had an apparent “pseudoprogression” after 3 BATs infusions, but achieved a CR after restarting capcitabine and is alive off therapy at 54 mos (24 mos after stopping capecitabine). Immune evaluations on the P1 patients show specific cytotoxicity to MiaPaCa-2 by peripheral blood mononuclear cells (PBMC) increased from 21% to 31% 2 weeks after the 3rd infusion, and IFN-γ EliSpots increased from < 20 to 1000 IFN-γ EliSpots/106 PBMC (p < 0.03). Patient IT 20121 (SD for 36 mos) increased IFN-γ EliSpots from 250 to 3200/106 PBMC after 8 infusions. Innate cytotoxicity responses in the P1 patients increased significantly after infusions (p < 0.04). Levels of IP-10 increased significantly (p < 0.04), and levels of IL-8 decreased but not significantly (p < 0.07). Conclusions: Infusions of BATs are safe and induce endogenous adaptive anti-tumor responses. Targeting PC with BATs may stabilize disease, leading to improved OS, as well as evidence that BATs infusions can induce anti-tumor activity and immunosensitize tumors to subsequent chemo. Clinical trial information: NCT014084,NCT03269526,NCT02620865.

Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients With Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma

2010 ◽  
Vol 28 (9) ◽  
pp. 1591-1598 ◽  
Author(s):  
Kazuhito Yamamoto ◽  
Atae Utsunomiya ◽  
Kensei Tobinai ◽  
Kunihiro Tsukasaki ◽  
Naokuni Uike ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Cell Lymphoma ◽  
Cell Leukemia ◽  
Peripheral T Cell Lymphoma ◽  
Adult T Cell Leukemia ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

Purpose KW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This phase I study assessed the safety, pharmacokinetics, recommended phase II dose and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL). Patients and Methods Sixteen patients received KW-0761 once a week for 4 weeks by intravenous infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg by a 3 + 3 design. Results Fifteen patients completed the protocol treatment. Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia (n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of toxicities increased with dose escalation. The maximum tolerated dose was not reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg. No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial (0.01; 2 at 1.0 mg/kg) responses. Conclusion KW-0761 was tolerated at all the dose levels tested, demonstrating potential efficacy against relapsed CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are thus warranted.

Phase I study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer

2015 ◽  
Vol 76 (3) ◽  
pp. 481-487 ◽  
Author(s):  
Yaman Suleiman ◽  
Amit Mahipal ◽  
David Shibata ◽  
Erin M. Siegel ◽  
Helen Jump ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Locally Advanced ◽  
Metastatic Pancreatic Cancer
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