Phase II Data on Paclitaxel and Docetaxel in Gastrointestinal Malignancies

1996 ◽  
pp. 425-430
Author(s):  
M. S. Aapro
Keyword(s):  
Phase Ii ◽  
Gastrointestinal Malignancies

A phase I dose escalation study of pharmacobiologically based scheduling of capecitabine and mitomycin C (MMC) in patients with gastrointestinal solid malignancies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15154-15154 ◽  
Author(s):  
M. E. Hill ◽  
A. Campbell ◽  
K. Kosuri ◽  
J. Thomas ◽  
M. Villalona ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Therapeutic Index ◽  
Dose Escalation Study ◽  
Gastrointestinal Malignancies ◽  
Combination Methods ◽  
Phase Ii Studies ◽  
Solid Malignancies ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

15154 Background: A principal determinant of the therapeutic index of capecitabine-based treatment is the grade of thymidine phosphorylase(dThdPase) activity in malignant tissues. MMC, an agent that is active in gastrointestinal malignancies, produces significant upregulation of the dTHdPase starting 4–6 days after treatment and persisting for at least 10 days. On the basis of the time-dependency and transience of this upregulation, we performed a phase I study of capecitabine in combination with MMC. The aim was to determine the maximally tolerated dose of this combination. Methods: In this ongoing study, patients with advanced gastrointestinal solid malignancies received MMC on day 1 and capecitabine twice daily on days 8 and 21, every 4 weeks. The MMC dose was fixed at 6mg/m2, whereas capecitabine was escalated in successive patient cohorts. Patients were allowed to have had a maximum of 2 prior therapies for metastatic disease. The total cumulative dose of MMC was capped at 36 mg/m^2 to reduce the risk of cumulative toxicity. Results: So far 23 patients with a median age of 62 received capecitabine doses from 1000 to 2000 mg/m^2/d. The majority of the patients had at least 1 prior treatment (86%). Four patients were considered non-evaluable. No dose-limiting toxicities were observed as we reached our final dose level. Toxicities were generally mild with only 7 patients experiencing grade 3 toxicities and two experiencing grade 4 toxicities. The most common toxicities were fatigue (67%), nausea (43%), diarrhea (33%), and anemia (29%), and all toxicities were reversible. There were no objective responses; however, 32% of evaluable patients had prolonged stable disease (43% colorectal, 29% pancreas, 14% esophageal, and 14% gastric). Conclusions: Capecitabine in combination with MMC in the proposed schedule is well tolerated and has promising preliminary activity in various gastrointestinal malignancies. Recommended doses for phase II studies are capecitabine 1000 mg/m^2 twice daily and MMC 6 mg/m^2. This study is ongoing with 2 more patients being entered at the recommended phase II dose. No significant financial relationships to disclose.

A phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in low-grade neuroendocrine tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14554-e14554 ◽  
Author(s):  
Saurabh Rajguru ◽  
Sam Joseph Lubner ◽  
Daniel Mulkerin ◽  
William R. Schelman ◽  
Natalie Winterle ◽  
...  
Keyword(s):  
Disease Control ◽  
Histone Deacetylase ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Hdac Inhibitor ◽  
Phase Ii Study ◽  
Hdac Inhibitors ◽  
Low Grade ◽  
Gastrointestinal Malignancies ◽  
Grade 3

e14554 Background: Neuroendocrine tumors (NETs) are a diverse and rare group of neoplasms arising from the neuroendocrine system. The most common subtypes are pancreatic islet cell tumors and carcinoid tumors. Although they represent only 2% of all gastrointestinal malignancies, given their overall favorable prognosis, the prevalence is much higher. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in a variety of solid tumors in preclinical data. We have previously shown that in NET cells, HDAC inhibitors have resulted in increased Notch1 expression and subsequent inhibition of growth. Methods: A single arm phase II study was performed. Adult patients with histologically confirmed, metastatic, low-grade NETs and an ECOG performance status of ≤ 2 were treated with the oral HDAC inhibitor panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. Results: 15 patients were accrued and 13 were evaluable for response (66.7% male, age range 40-80 years old (mean 59.4 years old), 66.7% carcinoid, 33.3% pancreatic NET). The median number of prior therapies was 1 (range 0-2) and no patient had previously received everolimus. The response rate was 0%. The stable disease rate was 92.3% as defined by stability seen on the first CT scan. Median progression-free survival was 11.8 months. The 1 year PFS was 42%. Thrombocytopenia and fatigue were the most common treatment-related grade 3 toxicities. There was one grade 4 toxicity of thrombocytopenia. The study was stopped early at the planned interim analysis based on lack of meaningful clinical efficacy outlined in the Simon two-stage design. Conclusions: The HDAC inhibitor panobinostat had infrequent grade 3 and 4 events in this patient population and resulted in a large percentage of subjects with disease control. The disease control rate, however, needs to be considered in the context of the typical slow growth rate of NETs. These data alone do not support continued evaluation of HDAC inhibitors in low-grade NETs. This study was supported by Novartis.

A single-arm phase II trial of gemcitabine, oxaliplatin, and panitumumab in KRAS wild-type advanced biliary tract cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 255-255
Author(s):  
Marcus Smith Noel ◽  
Jill N. Allen ◽  
Thomas Adam Abrams ◽  
Matthew Yurgelun ◽  
Jason Edward Faris ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Gallbladder Perforation ◽  
Wild Type ◽  
Gastrointestinal Malignancies ◽  
Egfr Inhibition ◽  
Tract Cancer

255 Background: Biliary Tract Cancer (BTC) encompasses a group of aggressive, genetically heterogeneous tumors with limited systemic treatment options. Currently platinum and gemcitabine-based therapy is the standard first-line treatment. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRASwild-type genetic subtypes of colon cancer. Methods: Patients with histologically confirmed, previously untreated unresectable or metastatic KRAS wild type biliary tract or gallbladder adenocarcinoma with ECOG performance status (PS) 0-2 were eligible. Patients were treated with Panitumumab 6mg/kg, Gemcitabine (GEM) 1000 mg/m2 (10 mg/m2/min), Oxaliplatin (OX) 85 mg/m2on days 1 and 15 of each 28 day cycle. The primary objective was to determine the objective response rate (ORR) by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression free survival (PFS), and overall survival. Results: Of the 38 patients screened, 31 patients were found to have KRAS wild type genotype and enrolled. The median age was 61 years old, 55% males, 100% of patients had an ECOG PS of <1. Twenty-five patients had intrahepatic cholangiocarcinoma, and 3 each had extrahepatic and gall bladder carcinoma. Twenty-eight patients completed at least 2 cycles of therapy and were evaluable for response. The ORR was 50% (95% CI 23.8-76.2). With a median follow-up of 11 months, median PFS was 10.5 months (95% CI, 3.8 - 23.9 months) and median OS was 24.8 months (95% CI, 9.0 months-no upper bound). The most common grade 3 toxicities were fatigue 23%, anemia 23%, neuropathy 16%, elevated AST/ALT 16%, hyponatremia 13%, nausea 13%, rash 10%, neutropenia 7%, and hypomagnesemia 7%. Grade 4 toxicities included leukopenia 10%, and 1 case (3%) each of gallbladder perforation, hematoma, anemia, hyperkalemia, hyponatremia and hypokalemia. Conclusions: Completed analysis of this phase II study of GEMOX-panitumumab for KRAS wild type advanced BTC reveals encouraging results with promising response rates and PFS. The toxicity profiles were expected and manageable. Further investigation of this regimen and anti-EGFR therapy is warranted. Clinical trial information: NCT01308840.

Phase Ib trial of pembrolizumab and XL888 in patients with advanced gastrointestinal malignancies.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS526-TPS526 ◽  
Author(s):  
Mehmet Akce ◽  
Olatunji B. Alese ◽  
Walid Labib Shaib ◽  
Christina Sing-Ying Wu ◽  
Gregory B Lesinski ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Phase Ii ◽  
Colorectal Adenocarcinoma ◽  
Locally Advanced ◽  
Stage Iv ◽  
Heat Shock Protein 90 ◽  
Gastrointestinal Malignancies ◽  
Expansion Phase ◽  
Phase Ib ◽  
Recommended Phase Ii Dose

TPS526 Background: Heat shock protein 90 (HSP90) has a central role in modulating tumor microenvironment, inflammatory signaling pathways (NF-κB, HIF-1α and Jak-STAT), tumor antigen presentation and expression, PD-L1 expression and macrophage migration inhibitory factor (MIF) as well as cytokine production. Inhibitors of HSP90 have been shown in preclinical studies and in patient samples to exert anti-tumor effects and modulate signaling pathways. XL888 is a selective inhibitor of HSP90. Based on this preclinical rationale, we have developed a phase Ib/II trial to determine the recommended phase II dose, evaluate the safety, toxicity profile, preliminary antitumor activity, and immunogenicity of the XL888 and Pembrolizumab combination in previously treated patients with advanced gastrointestinal tumors. Methods: The phase Ib trial design is standard 3+3. XL888 is administered orally (PO) in three dose levels of 45 (DL1), 90 (DL2), 60 (only if DLT on DL2) mg twice weekly with pembrolizumab at 200 mg IV on day 1, in 21-day cycles. Eligible patients must have stage IV or locally advanced unresectable gastrointestinal adenocarcinomas who have failed at least one prior therapy (patients with colorectal adenocarcinoma must have previously received oxaliplatin, irinotecan, and fluoropyrimidine), age ≥18 years, ECOG PS 0-1, no prior anti PD-1 or anti-PD-L1 agent. After recommended phase II dose is established, an expansion phase will enroll 16 patients with pancreatic adenocarcinoma (Arm A) and 16 patients with colorectal adenocarcinoma (Arm B). Primary endpoint response rate. In the expansion phase patients will receive initial cycle (3 weeks) treatment with either pembrolizumab or pembrolizumab plus XL888 and then starting cycle 2 all patients receive the combination. Blood will be collected pre-treatment, post 1st and 2nd cycle. Eight patients in each arm will undergo pre and post treatment tumor biopsies. This design will enable us to evaluate the effects of pembrolizumab alone versus the combination. This study was activated in June 2017 and to date 4 patients were enrolled in dose escalation phase. The dose expansion phase is expected to start accrual in December 2017. Clinical trial information: NCT03095781.

Phase II study of safety, efficacy and pharmacokinetics of BXT-51072 in patients with mild-moderately active ulcerative colitis

2001 ◽  
Vol 120 (5) ◽  
pp. A280-A280
Author(s):  
S HANAUER ◽  
P MINER ◽  
A KESHAVARZIAN ◽  
E MORRIS ◽  
B SALZBERG ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Active Ulcerative Colitis

1326: Phase II Trial of Gemcitabine, Paclitaxel, and Cisplatin in Advanced Transitional Cell Carcinoma

2005 ◽  
Vol 173 (4S) ◽  
pp. 360-360
Author(s):  
Peter E. Clark ◽  
Diana Stindt ◽  
M. Craig Hall ◽  
Michele Harmon ◽  
James F. Lovato ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Transitional Cell
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