A phase I study of the VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK 222584) and gemcitabine in patients with advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4122-4122 ◽  
Author(s):  
T. Kuo ◽  
A. Fitzgerald ◽  
H. Kaiser ◽  
B. I. Sikic ◽  
G. A. Fisher
Keyword(s):  
Pancreatic Cancer ◽  
Tyrosine Kinase ◽  
Phase I ◽  
Tyrosine Kinase Inhibitor ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Advanced Pancreatic Cancer ◽  
Patient Cohort ◽  
Grade 3 ◽  
Dose Levels

4122 Background: The VEGF pathway is the predominant mediator of angiogenesis in pancreatic cancer. Vatalanib (PTK787/ZK 222584) is a small molecule tyrosine kinase inhibitor of all known VEGF receptors. We initiated a phase I study of vatalanib and gemcitabine for advanced pancreatic cancer. Methods: Patients with newly diagnosed unresectable or metastatic pancreatic adenocarcinoma were enrolled. Previous adjuvant chemoradiotherapy with fluorouracil was allowed. Gemcitabine was given by fixed-dose rate infusion weekly x 3 in a 28-day cycle, and vatalanib was given orally daily. Dose-limiting toxicities (DLT) are defined as any grade 3/4 toxicity during the first cycle. The dose levels are as follows: Results: To date, 11 patients are evaluable for toxicity (5M/6F; median age 62 years, range 40–82 years; median KPS 90%). Thus far, 42 cycles have been given, with a median of four cycles per patient. Two patients have experienced DLT. The first patient (cohort 1) experienced grade 3 diarrhea and hypokalemia and grade 4 neutropenia occurring simultaneously and treated without sequelae. The second patient (cohort 3) developed grade 3 deep vein thrombosis. Beyond the first cycle, grade 3 toxicities included neutropenia (1), anemia (3), thrombocytopenia (1), hypertension (2), diarrhea (1), hypokalemia (1), thrombosis (1), and proteinuria (1). Three of eleven patients (27%) did not complete treatment to the first evaluation timepoint (2 cycles); two discontinued due to toxicity and one discontinued due to disease progression. Two of eleven patients (18%) had a partial response by RECIST. Six of eleven patients (55%) had stable disease as the best response ranging from 2–6 months. Conclusions: The combination of gemcitabine and vatalanib is generally well-tolerated with most grade 3/4 toxicities occurring late in the treatment course. Antitumor responses have been observed at initial dose levels and accrual to the final cohort with BID dosing of vatalanib continues. [Table: see text] No significant financial relationships to disclose.

Vorolanib (X-82), an oral anti-VEGFR/PDGFR/CSF1R tyrosine kinase inhibitor, with everolimus in solid tumors: results of a phase I study

2021 ◽  
Author(s):  
Katrina S. Pedersen ◽  
Patrick M. Grierson ◽  
Joel Picus ◽  
A. Craig Lockhart ◽  
Bruce J. Roth ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Phase I ◽  
Tyrosine Kinase Inhibitor ◽  
Solid Tumors ◽  
Phase I Study ◽  
Kinase Inhibitor

scholarly journals Phase I Study of Bosutinib, a Src/Abl Tyrosine Kinase Inhibitor, Administered to Patients with Advanced Solid Tumors

2011 ◽  
Vol 18 (4) ◽  
pp. 1092-1100 ◽  
Author(s):  
Adil I. Daud ◽  
Smitha S. Krishnamurthi ◽  
Mansoor N. Saleh ◽  
Barbara J. Gitlitz ◽  
Mitesh J. Borad ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Phase I ◽  
Tyrosine Kinase Inhibitor ◽  
Solid Tumors ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Advanced Solid Tumors ◽  
Abl Tyrosine Kinase ◽  
Abl Tyrosine Kinase Inhibitor

scholarly journals Phase I Study of Rapid Alternation of Sunitinib and Regorafenib for the Treatment of Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors

2019 ◽  
Vol 25 (24) ◽  
pp. 7287-7293 ◽  
Author(s):  
César Serrano ◽  
Alessandro Leal ◽  
Yanan Kuang ◽  
Jeffrey A. Morgan ◽  
Constance M. Barysauskas ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Phase I ◽  
Tyrosine Kinase Inhibitor ◽  
Gastrointestinal Stromal Tumors ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Stromal Tumors

Phase I study of the EGFR tyrosine kinase inhibitor erlotinib in combination with docetaxel and radiation in locally advanced squamous cell cancer of the head and neck (SCCHN)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5545-5545 ◽  
Author(s):  
P. Savvides ◽  
S. S. Agarwala ◽  
J. Greskovich ◽  
A. Argiris ◽  
J. Bokar ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Phase I ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Stage Iii ◽  
Pharmacokinetic Studies ◽  
Concentration Data ◽  
Egfr Tyrosine Kinase Inhibitor ◽  
Egfr Tyrosine Kinase ◽  
Dose Levels

5545 Background: EGFR is highly expressed in SCCHN, representing a promising therapeutic target. Erlotinib (E) is an EGFR tyrosine kinase inhibitor that may potentiate the efficacy of concurrent radiation (RT) and docetaxel (D). We sought to establish the MTD, toxicities and preliminary efficacy of the combination of RT, D and E in patients (pts) with SCCHN. Methods: Patients with previously untreated stage III-IVB SCCHN were enrolled in a phase I dose-escalating study with standard once-daily RT (70.2 Gy, 1.8 Gy/day), weekly D for the duration of RT and daily E for two weeks prior, during and up to two years following RT. 4 dose levels (DL) were evaluated [D (mg/m2)/E (mg): 15/50, 15/100, 20/100, 20/150]. A 3+3 escalation design was followed. Pharmacokinetic studies (PK) were performed. Results: A total of 23 patients were enrolled (6 pts at each DL 1–3, 5 pts at DL4). Primary site: oral cavity (n = 1), pharynx (n = 15) and larynx (n = 7). 20 patients (87%) had stage IV disease. Three dose-limiting toxicities were observed, 1 at each DL (1–3), including a death within 30 days from last treatment (DL1), grade 3 mucositis resulting in holding RT (>5 days) (DL2) and grade 4 mucositis (DL3). No DLT to date on DL4 with 3/5 pts evaluable. In patients enrolled at DL 1–3 (n = 18), post concurrent chemoRT, best response was CR (n = 15), not evaluable (n = 2), death on study (n = 1). 3/3 pts who underwent planned neck dissection had a pathologic CR. 9 patients are currently receiving adjuvant E and 1 has completed the 2-year course. 3 patients have relapsed. Interpatient variability of E peak plasma concentrations measured after the first dose was observed at all dose levels: 458 ± 173 ng/mL (DL1), 686 ± 364 (DL2), 1017 ± 241 (DL3), 833 ± 222 (DL4) (mean ± s.d., n = 6, 6, 6, 2 at DL1–4 respectively). Adjuvant erlotinib plasma concentration data will be presented separately. No significant PK interaction of erlotinib with docetaxel was noted. Conclusions: The combination of daily erlotinib with weekly docetaxel and RT for pts with stage III-IVB SCCHN is feasible and active. A phase II trial is planned. Supported in part by NIH grants nos. CA62502 and M01 RR-000080. No significant financial relationships to disclose.

P-359 Results from a phase I study of the oral VEGF receptor tyrosine kinase inhibitor ZD6474, in patients with solid tumors

Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S182
Author(s):  
Catherine Wheeler ◽  
Hironobu Minami ◽  
Hiromichi Ebi ◽  
Makoto Tahara ◽  
Yasutsuna Sasaki ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Phase I ◽  
Tyrosine Kinase Inhibitor ◽  
Solid Tumors ◽  
Receptor Tyrosine Kinase ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Vegf Receptor ◽  
Receptor Tyrosine Kinase Inhibitor

A phase I study of pazopanib in combination with FOLFOX 6 or capeOx in subjects with colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4133-4133
Author(s):  
J. Brady ◽  
M. Middleton ◽  
R. S. Midgley ◽  
M. K. Mallath ◽  
P. Corrie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tyrosine Kinase ◽  
Phase I ◽  
Tyrosine Kinase Inhibitor ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Safety Data ◽  
Organ Function ◽  
Adequate Organ Function ◽  
Dose Limiting Toxicity

4133 Background: Pazopanib (paz) is a tyrosine kinase inhibitor of VEGFR-1, -2, -3, PDGF-α, -β, and c-kit. Inhibition of angiogenic pathways in combination with chemotherapy has been shown to benefit patients (pts) with colorectal cancer (CRC). Methods: Pts with previously untreated advanced or metastatic CRC and adequate organ function were assigned to paz with FOLFOX6 (FO) or capeOx (CO) by their physician. Doses of paz were escalated with full strength chemotherapy, starting at 400mg daily. The optimally tolerated regimen (OTR) was the combination dose at which <1/6 pts experienced dose-limiting toxicity (DLT). Results: Fifty pts were enrolled in FO (paz 400 mg, n=6; 800, 15), CO (400, 12; 800, 9) and reduced capecitabine (rc) CO (800, 8) cohorts: median age = 55.5, M/F = 37/13. Pts have remained on therapy for a median of 3 (range 0–17) months. Three pts remain on study. Safety data is available on 41. The most common AEs are summarized in the table below. The OTR was exceeded with CO in combination with 800 mg and 400 mg of pazopanib, but was not exceeded with 800 mg pazopanib when capecitabine was reduced to 850 mg/m2 twice daily or with FO with 800 mg pazopanib. Efficacy and pharmacokinetic analyses are ongoing. Conclusions: The OTRs were achieved at 800 mg paz with full-dose FO, and at 800mg paz with rcCO. [Table: see text] [Table: see text]

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